Mitochondrial uncouplers for treating diseases and disorders

Abstract

Disclosed herein are compounds and methods for treating a disease or disorder characterized by a mutation in KRAS and / or LKB 1.

Description

[0001] MITOCHONDRIAL UNCOUPLERS FOR TREATING DISEASES AND DISORDERS RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 565,802, filed March 15, 2024, the entire contents of which are incorporated herein by reference. STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under CA208642 and CA016042, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND Non-small cell lung cancer (NSCLC) is estimated to claim the lives of about 130,000 people in the US alone in 2022. Despite recent breakthroughs in targeted and immunotherapy, most patients with advanced NSCLC develop therapy resistant disease, leading to a 5-year survival rate of approximately 6%. Accordingly, there is an ongoing need to identify novel therapeutic and diagnostic approaches for this deadly disease. SUMMARY OF THE INVENTION In one aspect, the present disclosure provides compounds having a structure represented by Formula I: Formula (I) wherein A1and A2are each independently alkyl, aryl, or heteroaryl; each R1and R2is independently selected from alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, haloalkyl, hydroxyl, hydroxyalkyl, carboxyl, carbonate, acyl, acyloxy, ester, thioester, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, amino, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido; L1and L2are each independently alkyl, alkoxy, alkoxyalkyl, oxyalkyloxyalkyl, oxyalkylaminoalkyl, oxyalkylthioalkyl, aminoalkylaminoalkyl, aminoalkylthioalkyl, thioalkylaminoalkyl, or thioalkylthioalkyl; Raand Rbare each independently selected from H, alkyl, or aralkyl; Z- is an anion; n and m are each independently 0, 1, 2, 3, 4, or 5; and q is 1 or 2. In another aspect, the present disclosure provides pharmaceutical compositions comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In still another aspect, the present disclosure provides methods of treating a disease or disorder characterized by a mutation in KRAS in a subject in need thereof, comprising administering a compound of the present disclosure to the subject. In yet another aspect, the present disclosure provides methods of treating a disease or disorder characterized by a mutation in LKB1 in a subject in need thereof, comprising administering a compound of the present disclosure to the subject. In yet another aspect, the present disclosure provides methods of treating cancer in a subject in need thereof, comprising administering a compound disclosed herein to the subject. In yet another aspect, the present disclosure provides methods of treating non-small cell lung cancer in a subject in need thereof, comprising administering a compound disclosed herein to the subject. DESCRIPTION OF THE DRAWINGS FIGs. 1A-1B show targeting mitochondria in therapy-resistant KRAS / LKB1 mutant lung tumors. FIG.1A shows a schematic of the proposed study to use18F-BnTP PET imaging to measure mitochondrial activity and ΔΨ in lung tumors and guide the targeted delivery of mitochondrial inhibitors. FIG.1B shows an overview of the aims to be tested in the study. Aim 1 will test selective induction of apoptosis with novel TPP-Benzethonium (TPP-Benz) compounds. Aim 2 will use the DARTS platform to identify mitochondrial proteins that bind TPP-Benz at high affinity. FIG.2 contains images showing18F-BnTP guided treatment using TPP-Benz. FIGs.3A- 3E show that18F-BnTP is a voltage sensitive mitochondrial specific in vivo probe. FIG.3A shows a schematic drawing representing voltage dependent uptake of18F-BnTP into the mitochondria. Inhibition of the Electron Transport Chain (ETC) with Complex I or V inhibitors. FIG. 3B shows18F-BnTP uptake (%ID / g tumor / heart ratio) measured in18F- BnTPPOSlung adenocarcinomas (LUAD) vs.18F-BnTPNEGlung squamous cell carcinomas (LUSC) from Kras / Lkb1 GEMMs. OXPHOS high vs low cutoff based on %ID / g shown as dotted line. FIG.3C shows bar graphs showing Complex I activity between LUAD vs LUSC tumor cells. FIG.3D shows a schematic drawing of the transthoracic (TT) implantation of KPL lung adenocarcinoma (LUAD) cells into syngeneic recipient mouse, imaging and treatment regiments. FIG.3E shows a waterfall plot for % change in18F-BnTP uptake before and after treatment for mice treated with a single dose of Vehicle (n = 7 mice) or 0.25 mg / kg Oligomycin (n = 9 mice) or 0.5 mg / kg Rotenone (n = 7 mice). Statistical significance was calculated using one way ANOVA. FIGs. 4A-4F show development of a HTS screen to identify pro-apoptotic OXPHOS inhibitors targeting KRAS / LKB1 mutant NSCLC. FIG. 4A shows a schematic of the H.T.S. design and in vivo validation. FIG. 4B shows IC50’s of OXPHOS inhibitor (OXPHOSi) Benzethonium (Benz) performed on KrasG12D; p53- / -(KP) and KrasG12D; p53- / -; Lkb1- / -(KPL) mouse lung tumors cell lines. FIG. 4C shows bar graphs showing KP and KPL lung tumors lines untreated (NT) or treated with Benz and analyzed by TMRE dye. FIG. 4D shows bar graphs showing apoptosis measured by cleaved caspase 3 / 7 in KP and KPL cells after NT or Benz. FIG.4E shows immunoblot of KP and KPL mutant cells untreated or treated with Benz (1µM) for 24 hours and probed for the indicated antibodies. FIG.4F shows viability of a panel KRAS (LKB1WT) and KRAS / LKB1 mutant human NSCLC lines untreated or treated with Benz (1µM) for 72 hours. FIGs.5A-5D show screen of TPP-Benz derivatives in KRAS mutant lung cancer cell lines. FIG.5A shows bar graphs showing cell viability WST1 assay performed on KrasG12D; p53- / -(KP) and KrasG12D; p53- / -; Lkb1- / -(KPL) mouse lung tumors cell lines. Cells treated for 24 hours with vehicle, Benzethonium (Benz 10µM), Phenformin (2mM) or 46 TPP-Benz derivatives (JHSW001 to JHSWm11) (10µM). FIG.5B shows bar graphs showing apoptosis measured by cleaved caspase 3 / 7 in human and mouse tumor and normal cells after 24 hours of treatment with vehicle, Benz, Phenformin, or TPP-Benz derivatives indicated. TPP-Benz lead compounds shown in box. KP, KPL and wildtype mouse embryonic fibroblasts (MEF17 WT) cells tested. FIG.5C shows bar graphs showing apoptosis measured by cleaved caspase 3 / 7 in human and mouse tumor and normal cells after 24 hours of treatment with vehicle, Benz, Phenformin, or TPP-Benz derivatives indicated. Normal AML1 cell lines tested. FIG. 5D shows bar graphs showing apoptosis measured by cleaved caspase 3 / 7 in human and mouse tumor and normal cells after 24 hours of treatment with vehicle, Benz, Phenformin, or TPP- Benz derivatives indicated. HBEC cell lines tested. FIGs. 6A-6B show JHSW compounds bind to the Mitochondrial Calcium Uniporter (MCU). FIG. 6A shows a schematic of the localization of the MCU channel in the mitochondrial inner membrane (IMM) (left) and the regulatory subunits to of the MCU that regulate Ca2+flux into the IMM. FIG. 6B shows a CETSA analysis of the MCU protein following binding to JHSW compound(s) denoted as (T) or vehicle denoted as (C) during increased temperatures. FIGs. 7A-7G show that high protein expression of the Mitochondrial Calcium Uniporter Regulator 1 (MCUR1) gene mediates selective sensitivity of lung cancer cell lines to JHSW analogs. FIG.7A shows IC50 values (µM) of lung cancer cells treated with JHSW 29 or 34 analogs vs parent compound Benzethonium (Benz) for 72 hrs. MCUR1 high expressing cells outlined in black and MCUR1 low expressing cells outlined in grey. FIG. 7B shows immunoblots of lung cancer cell lines probed for MCUR1 protein expression. B-actin included as a loading control. FIG.7C shows immunoblots of additional lung cancer cell lines probed for MCUR1 protein expression. B-actin included as a loading control. FIG. 7D shows immunoblots of lung cancer cell line H1703 after CRISPR sgRNA knockdown of MCUR1 (MCUR1 KO) vs empty vector (EV). FIG.7E shows the cell viability of MCUR1 wildtype vs KO H1703 isogenic cell lines treated with JHSW-29 or DMSO (control). MCUR1 knockdown negated JHSW mediated killing of cells. FIG. 7F shows the overexpression of MCUR1 (MCUR1-OE) in MCUR1LOH2170 cell lines. FIG. 7G shows the cell viability of H2170 MCUR1-OE vs Parental control cell lines. IC50values for isogenic H2170 cell lines treated with JHSW analogs. FIGs.8A-8B show that JHSW compounds inhibit calcium flux into the mitochondrial inner membrane in a MCUR1 dependent manner. FIG. 8A shows that fluorescence emitted from the Ca2+sensitive Mitycam reporter was measured in cells as a readout of Ca2+influx into the inner mitochondrial membrane (IMM). Caffeine is used to stimulate release of Ca2+into the IMM in either control or JHSW treated cells. Depicted is the measurement of Ca2+flux into the IMM in H1703 cells. Treatment of cells with 100nM of the JHSW-29 analog is shown. FIG. 8B shows that fluorescence emitted from the Ca2+sensitive Mitycam reporter was measured in cells as a readout of Ca2+influx into the inner mitochondrial membrane (IMM). Caffeine is used to stimulate release of Ca2+into the IMM in either control or JHSW treated cells. Depicted is the Ca2+flux into the IMM in H2170 cells. Treatment of cells with 100nM of the JHSW-29 analog is shown. FIGs. 9A-9F show a differential gene expression analysis of MCUR1 in normal and tumor tissues. FIG.9A shows a pan-cancer analysis of MCUR1 gene expression in numerous cancers vs healthy matched tissue. FIG. 9B shows a differential gene expression analysis of MCUR1 expression in lung adenocarcinomas vs normal healthy lung tissue. Student t-test used. Significance represented by p-value (P). FIG.9C shows a differential gene expression analysis of MCUR1 expression in lung squamous carcinomas vs normal healthy lung tissue. Student t- test used. Significance represented by p-value (P). FIG. 9D shows immunoblots of MCUR1 protein expression in patient tumors with lung adenocarcinomas (LUAD). Protein levels of MCU and vinculin were measured as well. FIG. 9E shows immunoblots of MCUR1 protein expression in patient tumors with lung squamous cell carcinomas (LUSC). Protein levels of MCU and vinculin were measured as well. FIG.9F shows immunoblots of MCUR1 protein expression in patient tumors with small cell lung cancer (SCLC), breast and bladder cancers. Protein levels of MCU and vinculin were measured as well. DETAILED DESCRIPTION OF THE INVENTION Metabolically active subsets of lung adenocarcinomas (LUADs) bearing mutations in KRAS and LKB1 have proven to be highly resistant to immunotherapy based approaches such as PD-1 pathway blockade. Patients bearing KRAS / LKB1 mutant LUADs represent a large lung cancer population for whom effective therapies are greatly needed. A different approach to the characterization and treatment of NSCLC is proposed, namely identification of conserved mitochondrial and metabolic signatures that can be precisely measured and exploited via newly pioneered approaches in this work. In one aspect, the present disclosure provides compounds having a structure represented by Formula (I), Formula (I) wherein, A1and A2are each independently alkyl, aryl, or heteroaryl; each R1and R2is independently selected from alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, haloalkyl, hydroxyl, hydroxyalkyl, carboxyl, carbonate, acyl, acyloxy, ester, thioester, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, amino, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido; L1and L2are each independently alkyl, alkoxy, alkoxyalkyl, oxyalkyloxyalkyl, oxyalkylaminoalkyl, oxyalkylthioalkyl, aminoalkylaminoalkyl, aminoalkylthioalkyl, thioalkylaminoalkyl, or thioalkylthioalkyl; Raand Rbare each independently selected from H, alkyl, or aralkyl; Z- is an anion; n and m are each independently 0, 1, 2, 3, 4, or 5; and q is 1 or 2. In certain embodiments, A1is aryl. In some such embodiments, R1is alkyl. In certain embodiments, A1is phenyl. In certain such embodiments, R1is trimethylpentyl. In certain embodiments, the compound has a structure represented by Formula (Ia), (Ia). In certain embodiments, L1is O(CH2)x1(O)y1(CH2)z1 and x1, y1, and z1 are each independently 0, 1, 2, 3, 4, or 5. In some embodiments, x1 is 2, y1 is 1, and z1 is 2. In further embodiments, x1is 3, y1is 1, and z1is 2. In yet further embodiments, x1is 3, y1is 1, and z1is 3. In still further embodiments, x1 is 1, y1 is 0, and z1 is 1. In certain embodiments, Raand Rbare each alkyl. In some such embodiments, Raand Rbare each methyl or ethyl. In alternative embodiments, Rais alkyl (e.g., methyl) and Rbis aralkyl (e.g., benzyl). In certain embodiments, the compound has a structure represented by Formula (Ib), (Ib). In certain embodiments, L2is alkyl. In some embodiments, A2is aryl. In certain such embodiments, A2is phenyl. In certain embodiments, the compound has a structure represented by Formula (Ic), (Ic). In certain embodiments, R2is alkoxy (e.g., butoxy). Alternatively, R2may be arylalkoxy (e.g., phenyl ethyloxy). In other embodiments, R2is (cycloalkyl)alkoxy (e.g., cyclohexylmethoxy. In certain embodiments, R2is carbonate. In some embodiments, R2is hydroxyl. In some embodiments, R2is nitro. In certain embodiments, R2is halo. In some embodiments, R2is acyloxy. In certain embodiments, R2is substituted with at least one R3, wherein each R3is independently alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, hydroxyl, hydroxyalkyl, carboxyl, acyl (e.g., acetyl), ester, thioester, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, amino, aminoalkyl, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido. In certain such embodiments, R3is halo (e.g., bromo). Alternatively, R3may be hydroxyalkyl. In other embodiments, R3is alkyl (e.g., t-butyl). In further embodiments, R3is heteroaryl (e.g., pyridiniumyl or triazolyl). In yet further embodiments, R3is heterocyclyl (e.g., dioxanyl). In still further embodiments, R3is cyano. In some embodiments, R3is aralkoxy (e.g., benzyloxy). In certain embodiments, R3is arylacyl (e.g., phenylacyl). In certain embodiments, R3is further substituted with heterocyclyl (e.g., pyrolidinyl). In certain embodiments, R3is phosphoryl (e.g., triphenylphosphonium, tricyclohexylphosphonium, tritolylphosphonium, trimethoxyphenylphosphonium, diphenylmethylphosphonium, or dimethylphenylphosphonium). In certain embodiments, the compound has a structure represented by Formula (Id), (Id). In certain embodiments, R2is alkyl. In some embodiments, Rcand Rdare each alkyl. In certain such embodiments, Rcand Rdare each methyl. In certain embodiments, L3is O(CH2)x2(O)y2(CH2)z2and x2y2, and z2are each independently 0, 1, 2, 3, 4, or 5. In some embodiments, x2 is 1, y2 is 0, and z2 is 1. In further embodiments, x2 is 2, y2 is 1, and z2 is 2. In yet further embodiments, x2 is 3, y2 is 1, and z2 is 3. In some embodiments, R4is alkyl. In certain such embodiments, R4is trimethylpentyl. In certain embodiments, the compound is selected from: , , , , , , , ,

[0002] , , , , , , , , , , , , , In another aspect, the present disclosure provides pharmaceutical compositions comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In still another aspect, the present disclosure provides methods of treating a disease or disorder characterized by a mutation in KRAS in a subject in need thereof, comprising administering a compound of the present disclosure to the subject. In certain embodiments, the disease or disorder is further characterized by a mutation in LKB1. In yet another aspect, the present disclosure provides methods of treating a disease or disorder characterized by a mutation in LKB1 in a subject in need thereof, comprising administering a compound of the present disclosure to the subject. In some embodiments, the disease or disorder is further characterized by a mutation in KRAS. In certain embodiments, the disease or disorder is cancer. In certain embodiments, the cancer is lung cancer, such as non-small cell lung cancer. In yet another aspect, the present disclosure provides methods of treating cancer in a subject in need thereof, comprising administering a compound disclosed herein to the subject. In yet another aspect, the present disclosure provides methods of treating non-small cell lung cancer in a subject in need thereof, comprising administering a compound disclosed herein to the subject. Pharmaceutical Compositions The compositions and methods of the present invention may be utilized to treat an individual in need thereof. In certain embodiments, the individual is a mammal such as a human, or a non-human mammal. When administered to an animal, such as a human, the composition or the compound is preferably administered as a pharmaceutical composition comprising, for example, a compound of the invention and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline or other solvents or vehicles such as glycols, glycerol, oils such as olive oil, or injectable organic esters. In preferred embodiments, when such pharmaceutical compositions are for human administration, particularly for invasive routes of administration (i.e., routes, such as injection or implantation, that circumvent transport or diffusion through an epithelial barrier), the aqueous solution is pyrogen-free, or substantially pyrogen-free. The excipients can be chosen, for example, to effect delayed release of an agent or to selectively target one or more cells, tissues or organs. The pharmaceutical composition can be in dosage unit form such as tablet, capsule (including sprinkle capsule and gelatin capsule), granule, lyophile for reconstitution, powder, solution, syrup, suppository, injection or the like. The composition can also be present in a transdermal delivery system, e.g., a skin patch. The composition can also be present in a solution suitable for topical administration, such as a lotion, cream, or ointment. A pharmaceutically acceptable carrier can contain physiologically acceptable agents that act, for example, to stabilize, increase solubility or to increase the absorption of a compound such as a compound of the invention. Such physiologically acceptable agents include, for example, carbohydrates, such as glucose, sucrose or dextrans, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins or other stabilizers or excipients. The choice of a pharmaceutically acceptable carrier, including a physiologically acceptable agent, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition can be a selfemulsifying drug delivery system or a selfmicroemulsifying drug delivery system. The pharmaceutical composition (preparation) also can be a liposome or other polymer matrix, which can have incorporated therein, for example, a compound of the invention. Liposomes, for example, which comprise phospholipids or other lipids, are nontoxic, physiologically acceptable and metabolizable carriers that are relatively simple to make and administer. The phrase "pharmaceutically acceptable" is art-recognized, and is employed herein to refer to those compounds, materials, compositions, excipients, adjuvants, polymers and other materials, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. The phrase "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations. A pharmaceutical composition (preparation) can be administered to a subject by any of a number of routes of administration including, for example, orally (for example, drenches as in aqueous or non-aqueous solutions or suspensions, tablets, capsules (including sprinkle capsules and gelatin capsules), boluses, powders, granules, pastes for application to the tongue); absorption through the oral mucosa (e.g., sublingually); subcutaneously; transdermally (for example as a patch applied to the skin); and topically (for example, as a cream, ointment or spray applied to the skin). The compound may also be formulated for inhalation. In certain embodiments, a compound may be simply dissolved or suspended in sterile water. Details of appropriate routes of administration and compositions suitable for same can be found in, for example, U.S. Pat. Nos. 6,110,973, 5,763,493, 5,731,000, 5,541,231, 5,427,798, 5,358,970 and 4,172,896, as well as in patents cited therein. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, out of one hundred percent, this amount will range from about 1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, most preferably from about 10 percent to about 30 percent. Methods of preparing these formulations or compositions include the step of bringing into association an active compound, such as a compound of the invention, with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. Formulations of the invention suitable for oral administration may be in the form of capsules (including sprinkle capsules and gelatin capsules), cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), lyophile, powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and / or as mouth washes and the like, each containing a predetermined amount of a compound of the present invention as an active ingredient. Compositions or compounds may also be administered as a bolus, electuary or paste. To prepare solid dosage forms for oral administration (capsules (including sprinkle capsules and gelatin capsules), tablets, pills, dragees, powders, granules and the like), the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and / or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and / or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as, for example, cetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; (10) complexing agents, such as, modified and unmodified cyclodextrins; and (11) coloring agents. In the case of capsules (including sprinkle capsules and gelatin capsules), tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface- active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets, and other solid dosage forms of the pharmaceutical compositions, such as dragees, capsules (including sprinkle capsules and gelatin capsules), pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and / or microspheres. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. Liquid dosage forms useful for oral administration include pharmaceutically acceptable emulsions, lyophiles for reconstitution, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, cyclodextrins and derivatives thereof, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3- butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. Dosage forms for the topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that may be required. The ointments, pastes, creams and gels may contain, in addition to an active compound, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to an active compound, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the active compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel. The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. Pharmaceutical compositions suitable for parenteral administration comprise one or more active compounds in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents. Examples of suitable aqueous and nonaqueous carriers that may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents that delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsulated matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissue. For use in the methods of this invention, active compounds can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier. Methods of introduction may also be provided by rechargeable or biodegradable devices. Various slow release polymeric devices have been developed and tested in vivo in recent years for the controlled delivery of drugs, including proteinaceous biopharmaceuticals. A variety of biocompatible polymers (including hydrogels), including both biodegradable and non-degradable polymers, can be used to form an implant for the sustained release of a compound at a particular target site. Actual dosage levels of the active ingredients in the pharmaceutical compositions may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of factors including the activity of the particular compound or combination of compounds employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of the particular compound(s) being employed, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compound(s) employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the therapeutically effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the pharmaceutical composition or compound at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. By “therapeutically effective amount” is meant the concentration of a compound that is sufficient to elicit the desired therapeutic effect. It is generally understood that the effective amount of the compound will vary according to the weight, sex, age, and medical history of the subject. Other factors which influence the effective amount may include, but are not limited to, the severity of the patient's condition, the disorder being treated, the stability of the compound, and, if desired, another type of therapeutic agent being administered with the compound of the invention. A larger total dose can be delivered by multiple administrations of the agent. Methods to determine efficacy and dosage are known to those skilled in the art (Isselbacher et al. (1996) Harrison’s Principles of Internal Medicine 13 ed., 1814-1882, herein incorporated by reference). In general, a suitable daily dose of an active compound used in the compositions and methods of the invention will be that amount of the compound that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. If desired, the effective daily dose of the active compound may be administered as one, two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. In certain embodiments of the present invention, the active compound may be administered two or three times daily. In preferred embodiments, the active compound will be administered once daily. The patient receiving this treatment is any animal in need, including primates, in particular humans; and other mammals such as equines, cattle, swine, sheep, cats, and dogs; poultry; and pets in general. In certain embodiments, compounds of the invention may be used alone or conjointly administered with another type of therapeutic agent. The term “pharmaceutically acceptable acid addition salt” as used herein means any non-toxic organic or inorganic salt of any base compounds represented by Formula I. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulfuric and phosphoric acids, as well as metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Illustrative organic acids that form suitable salts include mono-, di-, and tricarboxylic acids such as glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, benzoic, phenylacetic, cinnamic and salicylic acids, as well as sulfonic acids such as p-toluene sulfonic and methanesulfonic acids. Either the mono or di-acid salts can be formed, and such salts may exist in either a hydrated, solvated or substantially anhydrous form. In general, the acid addition salts of compounds of Formula I are more soluble in water and various hydrophilic organic solvents, and generally demonstrate higher melting points in comparison to their free base forms. The selection of the appropriate salt will be known to one skilled in the art. Other non- pharmaceutically acceptable salts, e.g., oxalates, may be used, for example, in the isolation of compounds of Formula I for laboratory use, or for subsequent conversion to a pharmaceutically acceptable acid addition salt. The term “pharmaceutically acceptable basic addition salt” as used herein means any non-toxic organic or inorganic base addition salt of any acid compounds represented by Formula I or any of their intermediates. Illustrative inorganic bases which form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide. Illustrative organic bases which form suitable salts include aliphatic, alicyclic, or aromatic organic amines such as methylamine, trimethylamine and picoline or ammonia. The selection of the appropriate salt will be known to a person skilled in the art. The present disclosure includes the use of pharmaceutically acceptable salts of compounds of the invention in the compositions and methods of the present invention. In certain embodiments, contemplated salts of the invention include, but are not limited to, alkyl, dialkyl, trialkyl or tetra-alkyl ammonium salts. In certain embodiments, contemplated salts of the invention include, but are not limited to, L-arginine, benenthamine, benzathine, betaine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, ethylenediamine, N-methylglucamine, hydrabamine, 1H-imidazole, lithium, L- lysine, magnesium, 4-(2-hydroxyethyl)morpholine, piperazine, potassium, 1-(2- hydroxyethyl)pyrrolidine, sodium, triethanolamine, tromethamine, and zinc salts. In certain embodiments, contemplated salts of the invention include, but are not limited to, Na, Ca, K, Mg, Zn or other metal salts. In certain embodiments, contemplated salts of the invention include, but are not limited to, 1-hydroxy-2-naphthoic acid, 2,2-dichloroacetic acid, 2- hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, acetic acid, adipic acid, l-ascorbic acid, l-aspartic acid, benzenesulfonic acid, benzoic acid, (+)-camphoric acid, (+)-camphor-10-sulfonic acid, capric acid (decanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, d-glucoheptonic acid, d-gluconic acid, d-glucuronic acid, glutamic acid, glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, l-malic acid, malonic acid, mandelic acid, methanesulfonic acid , naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, nitric acid, oleic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, proprionic acid, l-pyroglutamic acid, salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, l-tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, and undecylenic acid acid salts. The pharmaceutically acceptable acid addition salts can also exist as various solvates, such as with water, methanol, ethanol, dimethylformamide, and the like. Mixtures of such solvates can also be prepared. The source of such solvate can be from the solvent of crystallization, inherent in the solvent of preparation or crystallization, or adventitious to such solvent. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal-chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Definitions Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics and protein and nucleic acid chemistry, described herein, are those well known and commonly used in the art. The methods and techniques of the present disclosure are generally performed, unless otherwise indicated, according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout this specification. See, e.g. “Principles of Neural Science”, McGraw-Hill Medical, New York, N.Y. (2000); Motulsky, “Intuitive Biostatistics”, Oxford University Press, Inc. (1995); Lodish et al., “Molecular Cell Biology, 4th ed.”, W. H. Freeman & Co., New York (2000); Griffiths et al., “Introduction to Genetic Analysis, 7th ed.”, W. H. Freeman & Co., N.Y. (1999); and Gilbert et al., “Developmental Biology, 6th ed.”, Sinauer Associates, Inc., Sunderland, MA (2000). Chemistry terms used herein, unless otherwise defined herein, are used according to conventional usage in the art, as exemplified by “The McGraw-Hill Dictionary of Chemical Terms”, Parker S., Ed., McGraw-Hill, San Francisco, C.A. (1985). All of the above, and any other publications, patents and published patent applications referred to in this application are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control. The term “agent” is used herein to denote a chemical compound (such as an organic or inorganic compound, a mixture of chemical compounds), a biological macromolecule (such as a nucleic acid, an antibody, including parts thereof as well as humanized, chimeric and human antibodies and monoclonal antibodies, a protein or portion thereof, e.g., a peptide, a lipid, a carbohydrate), or an extract made from biological materials such as bacteria, plants, fungi, or animal (particularly mammalian) cells or tissues. Agents include, for example, agents whose structure is known, and those whose structure is not known. A “patient,” “subject,” or “individual” are used interchangeably and refer to either a human or a non-human animal. These terms include mammals, such as humans, primates, livestock animals (including bovines, porcines, etc.), companion animals (e.g., canines, felines, etc.) and rodents (e.g., mice and rats). “Administering” or “administration of” a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art. For example, a compound or an agent can be administered, intravenously, arterially, intradermally, intramuscularly, intraperitoneally, subcutaneously, ocularly, sublingually, orally (by ingestion), intranasally (by inhalation), intraspinally, intracerebrally, and transdermally (by absorption, e.g., through a skin duct). A compound or agent can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow or controlled release of the compound or agent. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods. Appropriate methods of administering a substance, a compound or an agent to a subject will also depend, for example, on the age and / or the physical condition of the subject and the chemical and biological properties of the compound or agent (e.g., solubility, digestibility, bioavailability, stability and toxicity). In some embodiments, a compound or an agent is administered orally, e.g., to a subject by ingestion. In some embodiments, the orally administered compound or agent is in an extended release or slow release formulation, or administered using a device for such slow or extended release. As used herein, the phrase “conjoint administration” refers to any form of administration of two or more different therapeutic agents such that the second agent is administered while the previously administered therapeutic agent is still effective in the body (e.g., the two agents are simultaneously effective in the patient, which may include synergistic effects of the two agents). For example, the different therapeutic compounds can be administered either in the same formulation or in separate formulations, either concomitantly or sequentially. Thus, an individual who receives such treatment can benefit from a combined effect of different therapeutic agents. A “therapeutically effective amount” or a “therapeutically effective dose” of a drug or agent is an amount of a drug or an agent that, when administered to a subject will have the intended therapeutic effect. The full therapeutic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a therapeutically effective amount may be administered in one or more administrations. The precise effective amount needed for a subject will depend upon, for example, the subject’s size, health and age, and the nature and extent of the condition being treated, such as cancer or MDS. The skilled worker can readily determine the effective amount for a given situation by routine experimentation. As used herein, the terms “optional” or “optionally” mean that the subsequently described event or circumstance may occur or may not occur, and that the description includes instances where the event or circumstance occurs as well as instances in which it does not. For example, “optionally substituted alkyl” refers to the alkyl may be substituted as well as where the alkyl is not substituted. It is understood that substituents and substitution patterns on the compounds of the present invention can be selected by one of ordinary skill in the art to result chemically stable compounds which can be readily synthesized by techniques known in the art, as well as those methods set forth below, from readily available starting materials. If a substituent is itself substituted with more than one group, it is understood that these multiple groups may be on the same carbon or on different carbons, so long as a stable structure results. As used herein, the term “optionally substituted” refers to the replacement of one to six hydrogen radicals in a given structure with the radical of a specified substituent including, but not limited to: hydroxyl, hydroxyalkyl, alkoxy, halogen, alkyl, nitro, silyl, acyl, acyloxy, aryl, cycloalkyl, heterocyclyl, amino, aminoalkyl, cyano, haloalkyl, haloalkoxy, -OCO-CH2-O- alkyl, -OP(O)(O-alkyl)2 or –CH2-OP(O)(O-alkyl)2. Preferably, “optionally substituted” refers to the replacement of one to four hydrogen radicals in a given structure with the substituents mentioned above. More preferably, one to three hydrogen radicals are replaced by the substituents as mentioned above. It is understood that the substituent can be further substituted. As used herein, the term “alkyl” refers to saturated aliphatic groups, including but not limited to C1-C10 straight-chain alkyl groups or C1-C10 branched-chain alkyl groups. Preferably, the “alkyl” group refers to C1-C6straight-chain alkyl groups or C1-C6branched- chain alkyl groups. Most preferably, the “alkyl” group refers to C1-C4 straight-chain alkyl groups or C1-C4 branched-chain alkyl groups. Examples of “alkyl” include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, n-butyl, sec-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, 1-octyl, 2-octyl, 3-octyl or 4-octyl and the like. The “alkyl” group may be optionally substituted. The term “acyl” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)-, preferably alkylC(O)-. The term “acylamino” is art-recognized and refers to an amino group substituted with an acyl group and may be represented, for example, by the formula hydrocarbylC(O)NH-. The term “acyloxy” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)O-, preferably alkylC(O)O-. The term “alkoxy” refers to an alkyl group having an oxygen attached thereto. Representative alkoxy groups include methoxy, ethoxy, propoxy, tert-butoxy and the like. The term “alkoxyalkyl” refers to an alkyl group substituted with an alkoxy group and may be represented by the general formula alkyl-O-alkyl. The term “alkyl” refers to saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. In preferred embodiments, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C1-30for straight chains, C3-30for branched chains), and more preferably 20 or fewer. Moreover, the term “alkyl” as used throughout the specification, examples, and claims is intended to include both unsubstituted and substituted alkyl groups, the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone, including haloalkyl groups such as trifluoromethyl and 2,2,2- trifluoroethyl, etc. The term “Cx-y” or “Cx-Cy”, when used in conjunction with a chemical moiety, such as, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy is meant to include groups that contain from x to y carbons in the chain. C0alkyl indicates a hydrogen where the group is in a terminal position, a bond if internal. A C1-6alkyl group, for example, contains from one to six carbon atoms in the chain. The term “alkylamino”, as used herein, refers to an amino group substituted with at least one alkyl group. The term “alkylthio”, as used herein, refers to a thiol group substituted with an alkyl group and may be represented by the general formula alkylS-. The term “amido”, as used herein, refers to a group O R9N R10, wherein R9and R10each independently represent a hydrogen or hydrocarbyl group, or R9and R10taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure. The terms “amine” and “amino” are art-recognized and refer to both unsubstituted and substituted amines and salts thereof, e.g., a moiety that can be represented by , wherein R9, R10, and R10’ each independently represent a hydrogen or a hydrocarbyl group, or R9and R10taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure. The term “aminoalkyl”, as used herein, refers to an alkyl group substituted with an amino group. The term “aralkyl”, as used herein, refers to an alkyl group substituted with an aryl group. The term “aryl” as used herein include substituted or unsubstituted single-ring aromatic groups in which each atom of the ring is carbon. Preferably the ring is a 5- to 7-membered ring, more preferably a 6-membered ring. The term “aryl” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is aromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like. The term “carbamate” is art-recognized and refers to a group ,wherein R9and R10independently represent hydrogen or a hydrocarbyl group. The term “carbocyclylalkyl”, as used herein, refers to an alkyl group substituted with a carbocycle group. The term “carbocycle” includes 5-7 membered monocyclic and 8-12 membered bicyclic rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated and aromatic rings. Carbocycle includes bicyclic molecules in which one, two or three or more atoms are shared between the two rings. The term “fused carbocycle” refers to a bicyclic carbocycle in which each of the rings shares two adjacent atoms with the other ring. Each ring of a fused carbocycle may be selected from saturated, unsaturated and aromatic rings. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, is included in the definition of carbocyclic. Exemplary “carbocycles” include cyclopentane, cyclohexane, bicyclo[2.2.1]heptane, 1,5-cyclooctadiene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]oct- 3-ene, naphthalene and adamantane. Exemplary fused carbocycles include decalin, naphthalene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]octane, 4,5,6,7-tetrahydro-1H- indene and bicyclo[4.1.0]hept-3-ene. “Carbocycles” may be substituted at any one or more positions capable of bearing a hydrogen atom. The term “carbocyclylalkyl”, as used herein, refers to an alkyl group substituted with a carbocycle group. The term “carbonate” is art-recognized and refers to a group -OCO2-. The term “carboxy”, as used herein, refers to a group represented by the formula -CO2H. The term “cycloalkyl” includes substituted or unsubstituted non-aromatic single ring structures, preferably 4- to 8-membered rings, more preferably 4- to 6-membered rings. The term “cycloalkyl” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is cycloalkyl and the substituent (e.g., R100) is attached to the cycloalkyl ring, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, pyrimidine, denzodioxane, tetrahydroquinoline, and the like. The term “ester”, as used herein, refers to a group -C(O)OR9wherein R9represents a hydrocarbyl group. The term “ether”, as used herein, refers to a hydrocarbyl group linked through an oxygen to another hydrocarbyl group. Accordingly, an ether substituent of a hydrocarbyl group may be hydrocarbyl-O-. Ethers may be either symmetrical or unsymmetrical. Examples of ethers include, but are not limited to, heterocycle-O-heterocycle and aryl-O-heterocycle. Ethers include “alkoxyalkyl” groups, which may be represented by the general formula alkyl-O-alkyl. The terms “halo” and “halogen” as used herein means halogen and includes chloro, fluoro, bromo, and iodo. The terms “hetaralkyl” and “heteroaralkyl”, as used herein, refers to an alkyl group substituted with a hetaryl group. The terms “heteroaryl” and “hetaryl” include substituted or unsubstituted aromatic single ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The terms “heteroaryl” and “hetaryl” also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heteroaromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. The term “heteroatom” as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, and sulfur. The term “heterocyclylalkyl”, as used herein, refers to an alkyl group substituted with a heterocycle group. The terms “heterocyclyl”, “heterocycle”, and “heterocyclic” refer to substituted or unsubstituted non-aromatic ring structures, preferably 3- to 10-membered rings, more preferably 3- to 7-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The terms “heterocyclyl” and “heterocyclic” also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heterocyclic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Heterocyclyl groups include, for example, piperidine, piperazine, pyrrolidine, morpholine, lactones, lactams, and the like. The term “hydrocarbyl”, as used herein, refers to a group that is bonded through a carbon atom that does not have a =O or =S substituent, and typically has at least one carbon- hydrogen bond and a primarily carbon backbone, but may optionally include heteroatoms. Thus, groups like methyl, ethoxyethyl, 2-pyridyl, and even trifluoromethyl are considered to be hydrocarbyl for the purposes of this application, but substituents such as acetyl (which has a =O substituent on the linking carbon) and ethoxy (which is linked through oxygen, not carbon) are not. Hydrocarbyl groups include, but are not limited to aryl, heteroaryl, carbocycle, heterocycle, alkyl, alkenyl, alkynyl, and combinations thereof. The term “hydroxyalkyl”, as used herein, refers to an alkyl group substituted with a hydroxy group. The term “lower” when used in conjunction with a chemical moiety, such as, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy is meant to include groups where there are ten or fewer atoms in the substituent, preferably six or fewer. A “lower alkyl”, for example, refers to an alkyl group that contains ten or fewer carbon atoms, preferably six or fewer. In certain embodiments, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy substituents defined herein are respectively lower acyl, lower acyloxy, lower alkyl, lower alkenyl, lower alkynyl, or lower alkoxy, whether they appear alone or in combination with other substituents, such as in the recitations hydroxyalkyl and aralkyl (in which case, for example, the atoms within the aryl group are not counted when counting the carbon atoms in the alkyl substituent). The terms “polycyclyl”, “polycycle”, and “polycyclic” refer to two or more rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls) in which two or more atoms are common to two adjoining rings, e.g., the rings are “fused rings”. Each of the rings of the polycycle can be substituted or unsubstituted. In certain embodiments, each ring of the polycycle contains from 3 to 10 atoms in the ring, preferably from 5 to 7. The term “sulfate” is art-recognized and refers to the group –OSO3H, or a pharmaceutically acceptable salt thereof. The term “sulfonamido” is art-recognized and refers to the group represented by the general formulae , wherein R9and R10independently represents hydrogen or hydrocarbyl. The term “sulfoxide” is art-recognized and refers to the group–S(O)-. The term “sulfonate” is art-recognized and refers to the group SO3H, or a pharmaceutically acceptable salt thereof. The term “sulfone” is art-recognized and refers to the group –S(O)2-. The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons of the backbone. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. Substituents can include any substituents described herein, for example, a halogen, a hydroxyl, a carbonyl (such as a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), an alkoxyl, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, a heterocyclyl, an aralkyl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. The term “thioalkyl”, as used herein, refers to an alkyl group substituted with a thiol group. The term “thioester”, as used herein, refers to a group -C(O)SR9or –SC(O)R9wherein R9represents a hydrocarbyl. The term “thioether”, as used herein, is equivalent to an ether, wherein the oxygen is replaced with a sulfur. The term “urea” is art-recognized and may be represented by the general formula ,wherein R9and R10independently represent hydrogen or a hydrocarbyl. The term “modulate” as used herein includes the inhibition or suppression of a function or activity (such as cell proliferation) as well as the enhancement of a function or activity. “Pharmaceutically acceptable salt” or “salt” is used herein to refer to an acid addition salt or a basic addition salt which is suitable for or compatible with the treatment of patients. Many of the compounds useful in the methods and compositions of this disclosure have at least one stereogenic center in their structure. This stereogenic center may be present in a R or a S configuration, said R and S notation is used in correspondence with the rules described in Pure Appl. Chem. (1976), 45, 11-30. The disclosure contemplates all stereoisomeric forms such as enantiomeric and diastereoisomeric forms of the compounds, salts, prodrugs or mixtures thereof (including all possible mixtures of stereoisomers). See, e.g., WO 01 / 062726. Furthermore, certain compounds which contain alkenyl groups may exist as Z (zusammen) or E (entgegen) isomers. In each instance, the disclosure includes both mixture and separate individual isomers. “Prodrug” or “pharmaceutically acceptable prodrug” refers to a compound that is metabolized, for example hydrolyzed or oxidized, in the host after administration to form the compound of the present disclosure (e.g., compounds of formula I). Typical examples of prodrugs include compounds that have biologically labile or cleavable (protecting) groups on a functional moiety of the active compound. Prodrugs include compounds that can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, dehydrolyzed, alkylated, dealkylated, acylated, deacylated, phosphorylated, or dephosphorylated to produce the active compound. Examples of prodrugs using ester or phosphoramidate as biologically labile or cleavable (protecting) groups are disclosed in U.S. Patents 6,875,751, 7,585,851, and 7,964,580, the disclosures of which are incorporated herein by reference. The prodrugs of this disclosure are metabolized to produce a compound of Formula I. The present disclosure includes within its scope, prodrugs of the compounds described herein. Conventional procedures for the selection and preparation of suitable prodrugs are described, for example, in “Design of Prodrugs” Ed. H. Bundgaard, Elsevier, 1985. The phrase “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filter, diluent, excipient, solvent or encapsulating material useful for formulating a drug for medicinal or therapeutic use. The term “Log of solubility”, “LogS” or “logS” as used herein is used in the art to quantify the aqueous solubility of a compound. The aqueous solubility of a compound significantly affects its absorption and distribution characteristics. A low solubility often goes along with a poor absorption. LogS value is a unit stripped logarithm (base 10) of the solubility measured in mol / liter. EXAMPLES The invention now being generally described, it will be more readily understood by reference to the following examples which are included merely for purposes of illustration of certain aspects and embodiments of the present invention and are not intended to limit the invention. Synthesis of Exemplary Compounds of the Disclosure All chemicals, reagents, and solvents were purchased from commercial sources when available and were used as received. When necessary, reagents and solvents were purified and dried by standard methods. Air- and moisture-sensitive reactions were carried out under an inert atmosphere of argon in oven-dried glassware.23 °C reactions were carried out at ambient temperature (approximately 23 °C). All reactions were monitored by thin layer chromatography (TLC) on precoated Merck 60 F334 silica gel plates with spots visualized by UV light (A = 254, 365) or by using an alkaline KMnO4 solution. Flash column chromatography (FC) was carried out on SiO260 (particle size 0.040- 0.063 mm, 230-400 mesh). Concentration under reduced pressure (in vacuo) was performed by rotary evaporation at 25-55 °C. Purified compounds were further dried under high vacuum or in a desiccator. Yields correspond to purified compounds, and were not further optimized. Proton nuclear magnetic resonance (1H NMR) spectra were recorded on Bruker spectrometers (at either 400 or 500 MHz). Carbon NMR (13C NMR) spectra were recorded on Bruker spectrometers (at either 400 or 500 MHz). NMR chemical shifts (δ ppm) were referenced to the residual solvent signals.1H NMR data are reported as follows: chemical shift in ppm; multiplicity (s = singlet, d = doublet t = triplet, q = quartet, quint =quintet, m = multiplet / complex pattern, br = broad signal); coupling constants (J) in Hz, integration. Data for13C NMR spectra are reported in terms of chemical shift, and. if applicable coupling constants. Electrospray ionization high-resolution mass spectrometry (ESI HR-MS) measurements were performed on Agilent 6545 LC / Q-TOF mass spectrometer. Experimental procedure for the preparation of JHSW-01 2-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)ethanol (1). 4-(2,4,4-Trimethylpentan-2- yl)phenol (0.05 mol), K2CO3(0.2 mol) and KI (0.006 mol) were dissolved in DMF(20 mL). Then 2- bromoethanol (0.1 mol) was added to the solution. The reaction mixture was stirred at 90 °C for 16 h. After cooling to 23 °C, the suspension was filtered and the solvent evaporated. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 10 / 1 to 4 / 1) to give 1 as a colorless oil (83% isolated yield). N,N-Dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2). A mixture of 2-dimethylaminoethyl chloride (30 mmol), 10M NaOH (20.6 mL), tetrabutylammonium bromide (TBAB, 2.4mmol) and 2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethanol 1 (12 mmol) in toluene (20.6 mL) was stirred vigorously at 80 °C for 18 h. Then the reaction mixture was cooled to 23 °C. The layers were separated, and the aqueous layer was extracted with toluene (2 × 20mL). The combined organic layers were washed successively with H2O and saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 9 / 1, MeCN / CHCl3 / Et3N, 1 / 1 / 0.01) to give 2 as a red liquid (63% yield). (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 6.81 (d, J = 8.0 Hz, 2H), 4.11 (t, J = 4.0 Hz, 2H), 3.81 (t, J = 4.0 Hz, 2H), 3.65 (t, J = 8.0 Hz, 2H), 2.53 (t, J = 8.0 Hz, 2H), 2.27 (s, 6H), 1.69 (s, 2H), 1.30 (s, 6H), 0.70 (s, 9H). HRMS m / z: [M+H]+calcd. For C20H36NO2+: 322.2746, found 322.2766. (4-(4-Bromobutoxy)phenyl)methanol (3). 1,4-Dibromobutane (24.2 mmol) and K2CO3 (32.2 mmol) were added to a solution of 4-hydroxybenzyl alcohol (12.1 mmol) in acetone (50 mL). After the reaction mixture was refluxed for 24 h, it was cooled to 23 °C. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 6 / 1) to give 3 as a colorless oil (91% yield). 1-(4-Bromobutoxy)-4-(bromomethyl)benzene (4). To a cooled (0 °C) solution of (4-(4- bromobutoxy) phenyl) methanol 3 (4 mmol) in anhydrous dichloromethane (4 mL) was added dropwise PBr3(4 mmol) in anhydrous dichloromethane (4 mL) under Ar. After being stirred at 23 °C for 2 h, the reaction mixture was quenched by water (4 mL) with cooling, and then neutralized with NaHCO3. The layers were separated, and the aqueous layer extracted with dichloromethane (2 × 4 mL). The combined organic layers were washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was used for the next step without further purification. N-(4-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)eth-anaminium bromide (JHSW-m-04). To a solution of N,N-dimethyl-2- (2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2, 0.5 mmol) in anhydrous dichloromethane was added 1-(4-bromo-butoxy)-4-(bromomethyl)benzene (4, 0.75 mmol) in anhydrous dichloromethane(4 mL). After being stirred at 23 °C for 8 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, MeCN / dichloromethane, 1 / 1) to give JHSW-m-04 as a light yellow oil (87% yield). 1H NMR (400 MHz, CD3CN) δ 7.45 (d, J= 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.53 (s, 2H), 4.12-4.10 (m, 2H), 4.01 (t, J = 8.0 Hz, 2H), 3.99-3.95 (m, 2H), 3.84-3.82 (m, 2H), 3.55-3.48 (m, 4H), 2.99 (s, 6H), 2.02-1.97 (m, 2H), 1.90-1.85 (m, 2H), 1.70 (s, 2H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.68, 156.40, 142.44, 134.75, 127.30, 119.49, 114.83, 113.62, 69.53, 68.35, 67.19, 66.93, 64.48, 62.70, 56.40, 50.06, 37.64, 33.91, 31.86, 31.09, 31.05, 29.28, 27.51. HRMS m / z: [M- Br]+calcd. For C31H49NO3Br+: 562.2891, found 562.2917. (4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)triphenylphosphonium formate (JHSW-01). To a solution of triphenylphosphine (1 mmol) in anhydrous MeCN (3 mL) was added N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04, 0.25 mmol) in anhydrous MeCN (3 mL) under Ar. After being stirred at 70 °C for 72 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in MeCN (0.5 ml) and Et2O (2 mL) was added. Th mixture was stirred at -10 °C for 30 min, filtered, and concentrated in vacuo. The residue was purified by HPLC (0.1% formic acid in water, 0.1% formic acid in MeCN), removed part of solvent in vacuo. Then the left solvent was removed under freeze-drying conditions to give JHSW-01 as a white solid as the diformate salt (48% yield). 1H NMR (400 MHz, D2O) δ 8.30 (s, 2H), 7.70-7.66 (m, 3H), 7.57-7.47 (m, 12H), 7.24 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 6.65 (d, J = 8.0 Hz, 2H), 4.28 (s, 2H), 4.09-4.08 (m, 2H), 3.96-3.91 (m, 4H), 3.76-3.75 (m, 2H), 3.35 (br m, 2H), 3.19- 3.12 (m, 2H), 2.84 (s, 6H), 1.83-1.68 (m, 4H), 1.32 (s, 2H), 0.93 (s, 6H), 0.29 (s, 9H).13C NMR (126 MHz, D2O) δ 169.04, 159.63, 155.48, 135.07, 134.74, 133.43, 130.17, 127.44, 119.73, 118.22, 117.53, 114.93, 113.88, 69.44, 68.35, 67.14, 66.57, 64.41, 62.43, 55.97, 50.20, 37.28, 31.37, 31.03, 30.90, 21.04, 20.63, 18.61.HRMS m / z: [M-HCOO]+calcd. For C50H65NO5P+: 790.4600, found 790.4672. Experimental procedure for the preparation of JHSW-02 (4-((7-Bromoheptyl)oxy)phenyl)methanol (6). Following the procedure for the preparation of (4-(4-bromobutoxy)phenyl)methanol (3), compound 6 was prepared from 1,7- dibromoheptane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 6 as a colorless oil (93% yield).1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.60 (s, 2H), 3.97 (t, J = 8.0 Hz, 2H), 3.41 (t, J = 8.0 Hz, 2H), 1.91-1.84 (m, 2H), 1.82-1.75 (m, 2H), 1.52-1.45 (m, 4H), 1.22-1.35 (m, 2H). HRMS m / z: [M-Br]+calcd. For C14H21O2Br: 300.0725, found 300.0743. 1-((7-Bromoheptyl)oxy)-4-(bromomethyl)benzene (7). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4) gave compound 7 as a colorless oil which was used for next step without further purification. N-(4-((7-Bromoheptyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (8). Following the procedure for the preparation of N-(4-(4-bromobutoxy)-benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) gave compound 8 as a light yellow oil (80% yield). 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 6.69 (d, J = 8.0 Hz, 2H), 4.85 (s, 2H), 4.05-4.02 (m, 4H), 3.89 (t, J = 8.0 Hz, 2H), 3.85-3.82 (m, 4H), 3.36 (t, J = 8.0 Hz, 2H), 3.21 (s, 6H), 1.85-1.78 (m, 2H), 1.74-1.69 (m, 2H), 1.62 (s, 2H), 1.45-1.38 (m, 4H), 1.36-1.30 (m, 2H), 1.26 (s, 6H), 0.63 (s, 9H). HRMS m / z: [M-Br]+calcd. For C34H55NO3Br+: 604.3360, found 604.3378. (7-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) heptyl)triphenylphosphonium bromide (JHSW-02). Following the procedure for the preparation of JHSW-01, the analogue JHSW- 02 was prepared from N-(4-((7-bromoheptyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethanaminium bromide (8, 0.25 mmol) and triphenylphosphine (1 mmol). The reaction mixture was concentrated in vacuo. The residue was dissolved in MeCN (0.5 mL) and Et2O (2 mL) was added. The mixture was stirred at -10 °C for 30 min and filtered. The purification process was repeated one more time, and the residue was concentrated in vacuo to give JHSW-02 as a light yellow solid as the bis-bromide salt (33% yield). 1H NMR (400 MHz, D2O) δ 7.67-7.65 (m, 3H), 7.56-7.50 (m, 12H), 7.24 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H), 4.29 (s, 2H), 4.04 (m, 2H), 3.89-3.84 (m, 4H), 3.74 (m, 2H), 3.32 (m, 2H), 3.04-3.00 (m, 2H), 2.83 (s, 6H), 1.52-1.33 (m, 6H), 1.17 (m, 4H), 1.01 (s, 6H), 0.37 (s, 9H).13C NMR (126 MHz, D2O) δ 155.62, 143.19, 134.87, 133.45, 130.17, 130.01, 127.33, 118.57, 118.44, 117.88, 117.75, 113.82, 69.26, 67.15, 64.58, 64.42, 62.42, 56.15, 51.74, 50.49, 37.43, 31.75, 31.28, 29.26, 29.14, 26.95, 24.98, 21.44, 21.35, 21.03. HRMS m / z: [M-2Br+HCOO]+calcd. For C53H71NO5P+: 832.5059, found 832.0714. Experimental procedure for the preparation of JHSW-03 Tricyclohexyl(4-(4-((dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)- λ4-azaneyl) methyl)phenoxy)butyl)phosphonium bromide formate (JHSW-03). Following the procedure for the preparation of JHSW-01, the analogue JHSW- 03 was prepared from JHSW-m-04 (0.25 mmol) and tricyclohexylphosphine (1 mmol) to give JHSW-03 as a white solid (45% yield). 1H NMR (400 MHz, D2O) δ 8.31 (s, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.0Hz, 2H), 6.69 (d, J = 8.0 Hz, 2H), 4.39 (s, 2H), 3.98-3.92 (m, 6H), 3.76 (m, 2H), 3.34 (m, 2H), 2.91 (s, 6H), 2.24-2.08 (m, 5H), 1.77-1.48 (m, 22H), 1.28-1.10 (m, 20H), 0.53 (s, 9H).13C NMR (126 MHz, D2O) δ 170.99, 159.88, 136.23, 134.89, 126.93, 126.84, 119.82, 114.92, 113.96, 69.51, 69.42, 68.12, 67.27, 66.10, 64.61, 55.68, 50.44, 37.64, 31.82, 31.70, 29.34, 29.02, 26.43, 26.17, 26.07, 25.05, 23.65, 18.36. HRMS m / z: [M-Br]+calcd. For C50H83NO5P+: 808.6003, found 808.6098. Experimental procedure for the preparation of JHSW-04 (4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)tris(4- methoxyphenyl)phosphonium formate (JHSW-04). Following the procedure for the preparation of JHSW-01, the analogue JHSW-04 was prepared from JHSW-m-04 (0.25 mmol) and tris(4-methoxyphenyl)phosphine (1 mmol) to give JHSW-04 as a white solid (46% yield). 1H NMR (400 MHz, D2O) δ 8.41 (s, 2H), 7.32-7.21 (m, 8H), 6.85 (m, 8H), 6.64-6.55 (m, 4H), 4.28 (s, 2H), 3.98-3.88 (m, 6H), 3.67-3.60 (m, 11H), 3.31 (m, 2H), 2.99 (m, 2H), 2.84 (s, 6H), 1.75-1.58 (m, 4H), 1.22 (s, 2H), 0.83 (s, 6H), 0.24 (s, 9H).13C NMR (126 MHz, D2O) δ 170.57, 164.17, 159.75, 135.16, 135.07, 134.66, 126.93, 119.66, 115.82, 114.74, 113.73, 109.36, 108.61, 69.37, 68.22, 67.03, 66.24, 64.53, 62.07, 56.31, 55.68, 50.27, 37.31, 31.60, 31.32, 31.17, 28.55, 21.82, 21.39. HRMS m / z: [M-HCOO]+calcd. For C53H71NO8P+: 880.4912, found 880.2856. Experimental procedure for the preparation of JHSW-05 (4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)(methyl)diphenylphosphonium bromide (JHSW-05). Following the procedure for the preparation of JHSW-01, the analogue JHSW-05 was prepared from JHSW-m-04 (0.25 mmol) and methyldiphenyl-phosphine (1 mmol). The reaction mixture was concentrated in vacuo. The residue was dissolved in MeCN (0.5ml) and Et2O (2ml) was added. The mixture was stirred at -10°C for 30 min and filtered. The purification process was repeated one more time, and the mixture was concentrated in vacuo to give JHSW-05 as a light yellow solid (39% yield). 1H NMR (400 MHz, D2O) δ 7.63-7.56 (m, 6H), 7.49-7.45 (m, 4H), 7.24 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 8.0 Hz, 2H), 4.29 (s, 2H), 4.05 (m, 2H), 3.89-3.87 (m, 4H), 3.74 (m, 2H), 2.84 (s, 6H), 2.79-2.74 (m, 2H), 2.31 (d, J = 12 Hz, 3H), 1.77-1.74 (m, 2H), 1.58-1.51 (m, 2H), 1.38 (s, 2H), 0.99 (s, 6H), 0.36 (s, 9H).13C NMR (126 MHz, D2O) δ 159.68, 155.66, 134.73, 132.09, 130.05, 129.95, 127.35, 119.67, 119.30, 118.62, 114.94, 113.92, 69.40, 68.32, 67.16, 66.65, 64.45, 62.38, 56.17, 50.23, 37.39, 31.53, 31.23, 31.10, 28.69, 28.57, 21.53, 21.10. HRMS m / z: [M-2Br+HCOO]+calcd. For C45H63NO5P+: 728.4438, found 728.4500. Experimental procedure for the preparation of JHSW-06 (4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)dimethyl(phenyl)phosphonium diformate (JHSW-06). Following the procedure for the preparation of JHSW-01, the analogue JHSW-06 was prepared from JHSW-m-04 (0.25 mmol) and dimethyl-(phenyl)phosphine (1 mmol) to give JHSW-06 as the diformate as a white solid (36% yield). 1H NMR (400 MHz, D2O) δ 8.23 (s, 2H), 7.66-7.54 (m, 3H), 7.48-7.44 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 8.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H), 4.27 (s, 2H), 4.02-4.00 (m, 2H), 3.89 (m, 2H), 3.81 (t, J = 8.0 Hz, 2H), 3.74-3.72 (m, 2H), 3.35- 3.33 (m, 2H), 2.82 (s, 6H), 2.40-2.32 (m, 2H), 2.01 (d, J = 16 Hz, 6H), 1.71-1.65 (m, 2H), 1.48- 1.42 (m, 2H), 1.36 (s, 2H), 0.98 (s, 6H), 0.35(s, 9H).13C NMR (126 MHz, D2O) δ 169.57, 159.74, 155.50, 143.52, 134.67, 130.94, 129.96, 127.47, 119.76, 119.62, 119.09, 114.93, 113.91, 69.38, 68.40, 67.11, 66.89, 64.41, 62.48, 56.07, 50.16, 37.37, 31.44, 31.11, 30.98, 28.81, 22.97, 22.56, 17.82. HRMS m / z: [M-HCOO]+calcd. For C40H61NO5P+: 666.4282, found 666.4316. Experimental procedure for the preparation of JHSW-07 1-(4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phen-oxy) butyl)pyridin-1-ium dibromide (JHSW-07). Following the procedure for the preparation of JHSW-01, the analogue JHSW- 07 was prepared from JHSW-m-04 (0.25 mmol) and pyridine (1 mmol). The reaction mixture was concentrated in vacuo. The residue was dissolved in MeCN (0.5 mL) and Et2O (1.5 mL) was added. The mixture was stirred at -10 °C for 30 min and filtered. The purification process was repeated one more time, and the mixture was concentrated in vacuo to give JHSW-07 as a light yellow solid (29% yield). 1H NMR (500 MHz, D2O) δ 8.74 (d, J = 5.0 Hz, 2H), 8.43-8.39 (m, 1H), 7.93 (t, J = 5.0 Hz, 2H), 7.30 (d, J =10.0 Hz, 2H), 7.18 (d, J =10.0 Hz, 2H), 6.87 (d, J =10.0 Hz, 2H), 6.75 (d, J =10.0 Hz, 2H), 4.56 (t, J = 5.0 Hz, 2H), 4.32 (s, 2H), 4.13-4.11 (m, 2H), 4.01-3.98 (m, 2H), 3.94 (m, 2H), 3.79-3.78 (m, 2H), 3.41-3.39 (m, 2H), 2.87 (s, 6H), 2.11-2.05 (m, 2H), 1.76-1.71 (m, 2H), 1.51 (s, 2H), 1.11 (s, 6H), 0.46 (s, 9H).13C NMR (126 MHz, D2O) δ 159.73, 155.47, 145.68, 144.18, 134.68, 128.28, 128.22, 127.56,119.66, 115.02, 114.00, 69.36, 68.49, 67.40, 67.14, 64.38, 62.60, 61.46, 56.08, 50.14, 37.40, 31.44, 31.10, 31.00, 27.54, 24.95.HRMS m / z: [M]2+calcd. for C36H54N2O32+: 281.2062, found 281.2168. Experimental procedure for the preparation of JHSW-08 (4-((7-Bromoheptyl)oxy)phenyl)methanol (9). Following the procedure for the preparation of (4-(4-bromobutoxy)phenyl)methanol (3), compound 9 was prepared from 1,3- dibromopropane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 9 as a colorless oil (90% yield).. 1-(Bromomethyl)-4-(3-bromopropoxy)benzene (10). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4), compound 9 gave 10 as a colorless oil used for next step without further purification. N-(4-(3-Bromopropoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethan-1-aminium bromide (JHSW-m-12). Following the procedure for the preparation of JHSW-m-04, compounds 2 and 10 gave JHSW-m-12 as a light yellow oil (87% yield). 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J =10.0 Hz, 2H), 7.25 (d, J =10.0 Hz, 2H), 6.91 (d, J = 10.0 Hz, 2H), 6.75 (d, J =10.0 Hz, 2H), 4.90 (s, 2H), 4.12-4.10 (m, 6H), 4.10-3.99 (m, 2H), 3.90-3.88 (m, 2H), 3.60 (t, J = 5.0 Hz, 2H), 3.27 (s, 6H), 2.35-2.30 (m, 2H), 1.69 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ160.61, 155.92, 143.08, 134.87, 127.31, 119.08, 115.10, 113.56, 70.05, 69.07, 68.93, 66.79, 65.42, 62.69, 56.93, 50.41, 38.00, 32.33, 32.10, 31.77, 31.65, 29.74. HRMS m / z: [M-Br]+calcd. for C30H47NO3+: 548.2739, found 548.2847. (3-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) propyl)triphenylphosphonium diformate (JHSW-08). Following the procedure for the preparation of JHSW-01, the analogue JHSW-08 was prepared from JHSW-m-12 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-08 as the diformate as a white solid (48% yield). 1H NMR (400 MHz, D2O) δ 8.22 (s, 2H), 7.62-7.57 (m, 3H), 7.51-7.39 (m, 12H), 7.21 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.0 Hz, 2H), 6.59 (d, J = 8.0 Hz, 2H), 4.27 (s, 2H), 3.96-3.87 (m, 6H), 3.70 (m, 2H), 3.30-3.18 (m, 4H), 2.83 (s, 6H), 1.92-1.90 (m, 2H), 1.27 (s, 2H), 0.88 (s, 6H), 0.28 (s, 9H).13C NMR (126 MHz, D2O) δ 169.29, 159.20, 155.81, 142.70, 135.13, 133.34, 130.23, 127.14, 119.90, 117.98, 117.29, 114.92, 113.80, 69.35, 68.26, 67.03, 66.52, 64.44, 62.16, 56.24, 50.27, 37.39, 31.62, 31.35, 31.19, 21.79, 18.96. HRMS m / z: [M-HCOO]+calcd. for C49H63NO5P+: 776.4433, found 776.4471. Experimental procedure for the preparation of JHSW-09 (4-((5-Bromopentyl)oxy)phenyl)methanol (11). Following the procedure for the preparation of (4-(4-bromobutoxy)phenyl)methanol (3), compound 11 was prepared from 1,5- dibromopentane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 11 as a colorless oil (94% yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.60 (d, J = 4.0 Hz, 2H), 4.00-3.95 (m, 2H), 3.44 (t, J = 8.0 Hz, 2H), 2.17-1.59 (m, 6H). HRMS m / z: [M+H]+calcd. for C12H18O2Br+: 273.0490, found 273.0496. 1-(Bromomethyl)-4-((5-bromopentyl)oxy)benzene (12). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4), reaction of 11 gave 12 as a colorless oil which was used for the next step without further purification. N-(4-((5-Bromopentyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (13). Following the procedure for the preparation of N-(4-(4-bromobutoxy)-benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) to, reaction of 12 with 2 gave 13 as a light yellow oil (82% yield). 1H NMR (400 MHz, D2O) δ 7.52 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.94 (s, 2H), 4.10-4.08 (m, 4H), 3.99-3.94 (m, 4H), 3.89-3.87 (m, 2H), 3.45-3.41 (m, 2H), 3.28 (s, 6H), 1.96-1.77 (m, 4H), 1.67 (s, 2H), 1.65-1.58 (m, 2H), 1.31 (s, 6H), 0.68 (s, 9H). HRMS m / z: [M-Br]+calcd. for C32H51NO3Br+: 576.3047, found 576.3095. (5-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) pentyl)triphenylphosphonium diformate (JHSW-09). Following the procedure of preparation of JHSW-01. JHSW-09 was prepared from N-(4-((5-bromopentyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethyl pentan-2-yl)phenoxy)ethoxy)ethanaminium bromide (13, 0.25 mmol) and triphenylphosphine (1 mmol) to give the desired product JHSW-09 as a white solid (38% yield). 1H NMR (400 MHz, D2O) δ 8.26 (s, 2H), 7.65 (m, 3H), 7.53-7.48 (m, 12H), 7.23 (d, J = 8.0 Hz, 2H), 6.99 (m, 2H), 6.69-6.63 (m, 4H), 4.29 (s, 2H), 4.03 (m, 2H), 3.90 (m, 2H), 3.81- 3.74 (m, 4H), 3.33 (m, 2H), 3.05 (m, 2H), 2.84 (s, 6H), 1.58-1.49 (m, 6H), 1.35 (m, 2H), 0.95 (s, 6H), 0.32 (s, 9H).13C NMR (126 MHz, D2O) δ 170.06, 159.84, 155.79, 142.77, 135.09, 133.34, 130.20, 127.19, 119.56, 118.23, 117.54, 114.84, 113.83, 69.40, 68.27, 67.71, 67.08, 64.46, 62.09, 56.26, 50.29, 42.73, 37.41, 31.63, 31.35, 27.27, 26.74, 21.49, 21.14. HRMS m / z: [M-HCOO]+calcd. for C51H67NO5P+: 804.4746, found 804.4370. Experimental procedure for the preparation of JHSW-10 (4-((6-Bromohexyl)oxy)phenyl)methanol (14). Following the procedure for the preparation of (4-(4-bromobutoxy)phenyl)methanol (3), compound 14 was prepared from 1,6- dibromohexane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 14 as a colorless oil (90% yield). 1-((6-Bromohexyl)oxy)-4-(bromomethyl)benzene (15). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4), reaction of 14 gave 15 as a colorless oil which used for the next step without further purification. N-(4-((6-Bromohexyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (16). Following the procedure for the preparation of N-(4-(4-bromobutoxy)-benzyl) -N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04), reaction of 2 and 15 gave 16 as a light yellow oil (79% yield). 1H NMR (500 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 4.92 (s, 2H), 4.11-4.09 (m, 4H), 3.96-3.94 (m, 4H), 3.89-3.88 (m, 2H), 3.42 (t, J = 4.0 Hz, 2H), 3.28 (s, 6H), 1.90-1.86 (m, 2H), 1.82-1.78 (m, 4H), 1.68 (s, 2H), 1.52-1.49 (m, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (126 MHz, CDCl3) δ 160.93, 155.95, 143.01, 134.87, 127.28, 118.76, 115.02, 113.58, 70.04, 69.14, 67.93, 66.84, 65.45, 62.62, 56.93, 50.46, 37.99, 33.79, 32.63, 32.33, 31.78, 31.65, 28.94, 27.89, 25.26. HRMS m / z: [M-Br]+calcd. for C34H55NO3Br+: 604.3360, found 604.3378. (6-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) hexyl)triphenylphosphonium dibromide (JHSW-10). Following the procedure for the preparation of JHSW-01, JHSW-10 was prepared from JHSW-m-04 (0.25 mmol) and triphenylphosphine (1 mmol). The reaction mixture was concentrated in vacuo. The residue was dissolved in MeCN (0.5 ml) and Et2O (2 ml) was added. The mixture was stirred at -10 °C for 30 min and filtered. The purification process was repeated one more time, and the residue concentrated in vacuo to give JHSW-10 as a light yellow solid (39% yield). 1H NMR (400 MHz, D2O) δ 7.61-7.59 (m, 3H), 7.50-7.44 (m, 12H), 7.22 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 8.0 Hz, 2H), 4.27 (s, 2H), 3.93 (m, 2H), 3.85 (m, 2H), 3.72-3.70 (m, 4H), 3.27 (m, 2H), 3.08-3.01 (m, 2H), 2.82 (s, 6H), 1.41-1.28 (m, 8H), 1.17 (m, 2H), 0.96 (s, 6H), 0.36 (s, 9H).13C NMR (126 MHz, D2O) δ 159.93, 155.95, 135.05, 134.74, 133.37, 130.11, 127.10, 119.53, 118.30, 117.61, 114.86, 113.88, 69.38, 68.12, 67.89, 67.13, 64.50, 61.97, 56.42, 50.35, 37.47, 31.75, 31.49, 31.36, 29.21, 27.87, 24.53, 21.80, 21.02.HRMS m / z: [M-2Br+HCOO]+calcd. for C49H63NO5P+: 818.4902, found 818.4204. Experimental procedure for the preparation of JHSW-11 (4-((9-Bromononyl)oxy)phenyl)methanol (17). Following the procedure of preparation of (4-(4-bromo-butoxy)phenyl)methanol (3). Compound 17 was prepared from 1,9-dibromononane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 17 as a colorless oil (95% yield).1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.60 (d, J = 4.0 Hz, 2H), 3.95 (t, J = 8.0 Hz, 2H), 3.40 (t, J = 8.0 Hz, 2H), 1.89- 1.74 (m, 4H), 1.48-1.39 (m, 4H), 1.37-1.30 (m, 6H). HRMS m / z: [M+H]+calcd. for C16H26O2Br+: 329.1116, found 329.1133. 1-(Bromomethyl)-4-((9-bromononyl)oxy)benzene (18). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4), reaction of 17 gave 18 as a colorless oil, which was used for the next step without further purification. N-(4-((9-Bromononyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethan-1-aminium bromide (JHSW-m-06). Following the procedure for the preparation of N-(4-(4-bromo butoxy)benzyl) -N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04), reaction of 2 and 8 gave JHSW-m-06 as a light yellow oil (78% yield). 1H NMR (400 MHz, CD3CN) δ 7.47 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.63 (s, 2H), 4.11-4.09 (m, 2H), 3.98-3.95 (m, 4H), 3.84-3.82 (m, 2H), 3.57-3.55 (m, 2H), 3.44 (t, J = 8.0 Hz, 2H), 3.04 (s, 6H), 2.25-2.23 (m, 2H), 1.84-1.79 (m, 2H), 1.75-1.70 (m, 2H), 1.69 (s, 2H), 1.41-1.37 (m, 4H), 1.31-1.30 (m, 4H), 1.29 (s, 6H), 0.66 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.94, 155.28, 143.43, 134.73, 127.40, 119.21, 114.88, 113.82, 68.39, 68.10, 62.58, 61.72, 56.79, 56.34, 54.35, 50.08, 37.74, 34.41, 32.58, 31.87, 31.06, 29.04, 28.91, 28.79, 28.33, 27.76, 25.61, 23.34. HRMS m / z: [M- Br]+calcd. for C36H59NO3Br+: 632.3673, found 632.3697. (9-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) nonyl)triphenylphosphonium diformate (JHSW-11). Following the procedure for the preparation of JHSW-01, JHSW-11 was prepared from JHSW-m-06 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-11 as a white solid (41% yield). 1H NMR (400 MHz, D2O) δ 8.24 (s, 2H), 7.61-7.57 (m, 3H), 7.46-7.41 (m, 12H), 7.23 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 6.58 (d, J = 8.0 Hs, 4H), 4.25 (s, 2H), 3.87-3.82 (m, 4H), 3.65-3.61 (m, 4H), 3.19 (m, 2H), 2.98-2.91 (m, 2H), 2.82 (s, 6H), 1.38-1.19 (m, 8H), 1.04-0.91 (m, 14H), 0.40 (s, 9H).13C NMR (126 MHz, D2O) δ 169.69, 160.16, 156.30, 141.58, 135.15, 133.25, 130.25, 126.83, 119.59, 118.15, 117.47, 114.65, 113.82, 69.34, 67.91, 67.87, 67.01, 64.49, 61.38, 56.71, 50.52, 37.55, 31.97, 31.74, 31.61, 29.82, 28.73, 28.52, 28.25, 25.55, 21.97, 21.43, 21.02. HRMS m / z: [M-HCOO]+calcd. for C55H75NO5P+: 860.5378, found 860.3921. Experimental procedure for the preparation of JHSW-12 (3-(Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)propyl) triphenyl phosphonium dibromide (JHSW-12). A mixture of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethan-1- amine (2, 0.15 mmol) in MeCN (1mL) and (3-bromopropyl)triphenylphos-phonium bromide (0.20 mmol) in MeCN (6 mL) was stirred at 40 °C for 24 h. The reaction mixture was cooled to 23 °C and the solvent was removed in vacuo. The residue was washed with MeOH (2×1 mL) for 0.5 h, filtered, and concentrated in vacuo to give JHSW-12 as a light yellow solid (31% yield). 1H NMR (400 MHz, CD3CN) δ 7.88-7.83 (m, 3H), 7.78-7.67 (m, 12H), 7.22 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.00-3.98 (m, 2H), 3.89-3.88 (m, 2H), 3.81-3.75 (m, 4H), 3.51-3.40 (m, 4H), 3.09 (s, 6H), 2.08-2.03 (m, 2H), 1.68 (s, 2H), 1.27 (s, 6H), 0.65 (s, 9H).13C NMR (126 MHz, D2O) δ 155.90, 141.96, 135.24, 133.49, 130.46, 127.01, 117.49, 113.93, 69.45, 67.34, 64.47, 63.27, 62.12, 56.48, 52.48, 37.57, 31.96, 31.87, 31.73, 31.59, 16.37. HRMS m / z: [M-2Br]2+calcd. for C41H56NO2P2+: 312.7019, found 312.6206. Experimental procedure for the preparation of JHSW-13 (4-(Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)butyl)triphenyl phosphonium dibromide (JHSW-13). Following the procedure for the preparation of JHSW-12, JHSW-13 was prepared from N,N- dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (0.15 mmol) and (4-bromobutyl)triphenylphosphonium bromide (0.2 mmol) to give 13 as a light yellow solid (41% yield). 1H NMR (400 MHz, CD3CN) δ 7.85-7.75 (m, 9H), 7.71-7.69 (m, 6H), 7.24 (d, J = 8.0 Hz, 2H), 6.74 (d, J =8.0 Hz, 2H), 4.05-4.04 (m, 2H), 3.92 (m, 2H), 3.80-3.78 (m, 2H), 3.61- 3.53 (m, 6H), 3.11 (s, 6H), 2.07-2.00 (m, 2H), 1.69 (s, 2H), 1.66-1.62 (m, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (126 MHz, D2O) δ 159.67, 155.66, 134.72, 132.09, 130.05, 127.34, 118.62, 113.92, 69.39, 67.15, 66.64, 64.44, 62.38, 56.17, 50.22, 37.39, 31.53, 31.23, 31.10, 28.57, 21.10, 17.98. HRMS m / z: [M-2Br]2+calcd. for C42H58NO2P2+: 319.7097, found 319.7114. Experimental procedure for the preparation of JHSW-14 Tributyl(4-(4-((dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl) phenoxy)butyl)phosphonium formate (JHSW- 14). Following the procedure for the preparation of JHSW-01, JHSW-03 was prepared from JHSW-m-04 (0.25 mmol) and tributylphosphine (1 mmol) to give JHSW-14 as a white solid (35% yield). 1H NMR (400 MHz, D2O) δ 8.24 (s, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.0 Hz, 2H), 4.30 (s, 2H), 4.03 (m, 2H), 3.96-3.90 (m, 4H), 3.75 (m, 2H), 3.35 (m, 2H), 2.84 (s, 6H), 2.09-1.92 (m, 8H), 1.79-1.76 (m, 2H), 1.57- 1.55 (m, 2H), 1.46 (s, 2H), 1.46-1.22 (m, 12H), 1.07 (s, 6H), 0.71 (t, J = 4.0 Hz, 9H), 0.46 (s, 9H).13C NMR (126 MHz, D2O) δ 168.78, 159.80, 155.53, 143.57, 134.79, 127.52, 119.73, 114.93, 113.99, 69.40, 68.44, 67.15, 66.78, 64.40, 62.53, 56.13, 50.16, 37.43, 31.50, 31.17, 31.06, 28.86, 23.32, 22.71, 17.79, 17.41, 17.02, 12.56. HRMS m / z: [M-HCOO]+calcd. for C44H77NO5P+: 730.5534, found 730.5589. Experimental procedure for the preparation of JHSW-15 (4-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)tri-p-tolylphosphonium formate (JHSW-15). Following the procedure for the preparation of JHSW-01, JHSW-15 was prepared from JHSW-m-04 (0.25 mmol) and tri-p-tolylphosphine (1 mmol) to give JHSW-15 as a white solid (42% yield). 1H NMR (400 MHz, D2O) δ 8.24 (s, 2H), 7.31-7.23 (m, 8H), 7.18-7.17 (m, 6H), 6.82 (d, J = 8.0 Hz, 2H), 6.65 (d, J = 8.0 Hz, 2H), 6.56 (d, J = 8.0 Hz, 2H), 4.27 (s, 2H), 3.95 (m, 2H), 3.87-3.85 (m, 4H), 3.71 (m, 2H), 3.30 (m, 2H), 3.07-3.00 (m, 2H), 2.83 (s, 6H), 2.16 (s, 9H), 1.77 -1.74 (m, 2H), 1.61 -1.55 (m, 2H), 1.22 (s, 2H), 0.83 (s, 6H), 0.24 (s, 9H).13C NMR (126 MHz, D2O) δ 169.79, 159.74, 146.49, 134.70, 133.09, 133.01, 130.83, 130.73, 126.99, 119.67, 115.06, 114.35, 113.78, 69.39, 68.23, 67.04, 66.31, 64.50, 62.12, 56.26, 50.26, 37.31, 31.56, 31.31, 31.14, 28.57, 20.97, 20.79, 18.68.HRMS m / z: [M-HCOO]+calcd. for C53H71NO5P+: 832.5064, found 832.5089. Experimental procedure for the preparation of JHSW-16 (3-(4-Bromobutoxy)phenyl)methanol (19). Following the procedure for the preparation of (4-(4-bromo-butoxy)phenyl)methanol (3), compound 19 was prepared from 1,4- dibromobutane (24.2 mmol) and 3-(hydroxymethyl)phenol (12.1 mmol) to give 19 as a colorless oil (89% yield). 1H NMR (400 MHz, CDCl3) δ 7.29-7.23 (m, 1H), 6.99 -6.92 (m, 2H), 6.84 -6.81 (m, 1H), 4.46 (s, 2H), 4.02-3.98 (m, 2H), 3.49 (t, J = 8.0 Hz, 2H), 2.19-2.18 (m, 2H), 1.98-1.91 (m, 2H). HRMS m / z: [M+H]+calcd. for C11H16O2Br+: 259.0334, found 259.0362. 1-(4-Bromobutoxy)-3-(bromomethyl)benzene (20). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4), reaction of 19 gave 20 as a colorless oil which used for the next step without further purification. N-(3-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)eth-anaminium bromide (21). Following the procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) , reaction of 2 and 20 gave 21 as a light yellow oil (75% yield). 1H NMR (500 MHz, CDCl3) δ 7.31 (t, J = 8.0 Hz, 1H), 7.27-7.24 (m, 3H), 7.13 (d, J = 8.0 Hz, 1H), 6.99 - 6.96 (m, 1H), 6.75 (d, J = 8.0 Hz, 2H), 4.98 (s, 2H), 4.11-4.09 (m, 4H), 4.03-4.01 (m, 4H), 3.90-3.88 (m, 2H), 3.47 (t, J = 5.0 Hz, 2H), 3.33 (s, 6H), 2.08-2.02 (m, 2H), 1.96-1.90 (m, 2H), 1.67 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H). NMR (126 MHz, CDCl3) δ 159.31, 155.93, 143.04, 130.23, 128.46, 127.28, 125.42, 119.38, 116.94, 113.59, 70.04, 69.11, 67.30, 66.85, 65.33, 63.07, 56.93, 50.84, 43.85, 37.99, 33.52, 32.33, 31.77, 29.41, 27.79. HRMS m / z: [M-Br]+calcd. for C31H49NO3Br+: 562.2891, found 562.2935. (4-(3-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)triphenylphosphonium diformate (JHSW-16). Following the procedure for the preparation of JHSW-01, JHSW-16 was prepared from N-(3-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethyl pentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (21, 0.25 mmol) and triphenylphos-phine (1 mmol) to give JHSW-16 as a white solid (37% yield). 1H NMR (400 MHz, D2O) δ 8.25 (s, 2H), 7.64-7.59 (m, 3H), 7.50-7.42 (m, 12H), 7.13 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.89-6.86 (m, 3H), 6.80-6.77 (dd, J = 8.0, 4.0 Hz, 1H), 6.56 (d, J = 8.0 Hz, 2H), 4.28 (s, 2H), 3.98-3.96 (m, 2H), 3.89-3.87 (m, 4H), 3.71-3.70 (m, 2H), 3.35 (m, 2H), 3.17-3.09 (m, 2H), 2.85 (s, 6H), 1.79-1.75 (m, 2H), 1.65-1.62 (m, 2H), 1.28 (s, 2H), 0.88 (s, 6H), 0.28 (s, 9H).13C NMR (126 MHz, D2O) δ 169.89, 158.26, 155.73, 142.87, 135.08, 133.26, 130.10, 128.75, 127.15, 125.89, 118.92, 118.15, 117.46, 116.86, 113.87, 69.44, 68.40, 67.14, 66.65, 64.50, 62.56, 56.17, 50.69, 37.35, 31.55, 31.27, 31.12, 28.82, 20.71, 18.79. HRMS m / z: [M-HCOO]+calcd. for C50H65NO5P+: 790.4595, found 790.4613. Experimental procedure for the preparation of JHSW-17 1-(4-(3-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)-phenoxy)butyl)pyridin-1-ium diformate (JHSW-17). Following the procedure for the preparation of JHSW-01, JHSW-17 was prepared from N-(3-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethyl pentan- 2-yl)phenoxy)ethoxy)ethanaminium bromide (21, 0.25 mmol) and pyridine (1 mmol) to give JHSW-17 as a light yellow oil (40% yield). 1H NMR (400 MHz, D2O) δ 8.68 (d, J = 8.0 Hz, 2H), 8.36 (t, J = 8.0 Hz, 1H), 8.26 (s, 2H), 7.89 (t, J = 8.0 Hz, 2H), 7.22 (t, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 6.96-6.93 (m, 3H), 6.66 (d, J = 8.0 Hz, 2H), 4.50 (t, J = 8.0 Hz, 2H), 4.32 (s, 2H), 4.06 (m, 2H), 3.92-3.90 (m, 4H), 3.75 (m, 2H), 3.41-3.39 (m, 2H), 2.88 (s, 6H), 2.04-2.00 (m, 2H), 1.69-1.65 (m, 2H), 1.43 (s, 2H), 1.04 (s, 6H), 0.40 (s, 9H).13C NMR (126 MHz, D2O) δ 170.10, 158.31, 155.50, 145.73, 144.14, 143.61, 130.38, 128.60, 128.31, 127.46, 125.89, 119.18, 116.89, 114.02, 69.38, 68.63, 67.43, 67.22, 64.43, 62.92, 61.47, 56.10, 50.61, 37.40, 31.47, 31.13, 31.01, 27.59, 25.05. HRMS m / z: [M-HCOO]+calcd. for C37H55N2O5P+: 607.4105, found 607.4174. Experimental procedure for the preparation of JHSW-18 N-Benzyl-N-methyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanamine (22). Following the procedure of preparation of N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethan-amine (2), compound 22 was prepared from 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethanol (1, 2 mmol) and N-benzyl-2- chloro-N-methylethanamine (4 mmol) to give 22 as a yellow liquid (70% yield). 1H NMR (400 MHz, CDCl3) δ 7.32-7.30 (m, 4H), 7.29-7.26 (m, 1H), 7.25-7.23 (m, 2H), 6.81 (d, J = 12 Hz, 2H), 4.12-4.09 (m, 2H), 3.80 (t, J = 8.0 Hz, 2H), 3.69 (t, J = 8.0 Hz, 2H), 3.57 (s, 2H), 2.66 (t, J = 8.0 Hz, 2H), 2.28 (s, 3H), 1.70 (s, 2H), 1.34 (s, 6H), 0.71 (s, 9H). HRMS m / z: [M+H]+calcd. for C26H40NO2+: 398.3059, found 358.3068. (4-(Benzyl(methyl)(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)butyl)triphenyl phosphonium diformate (JHSW-18). Following the procedure for the preparation of JHSW-12, compound JHSW-18 was prepared from 22 (0.15 mmol) and (4-bromobutyl)triphenylphosphonium bromide (0.2 mmol) to give JHSW-18 as a light yellow solid (34% yield). 1H NMR (500 MHz, D2O) δ 8.33 (s, 2H), 7.79-7.75 (m, 3H), 7.61-7.57 (m, 6H), 7.64- 7.59 (m, 6H), 7.53-7.48 (m, 6H), 7.44 (t, J = 10.0 Hz, 1H), 7.38-7.32 (m, 4H), 7.10 (d, J = 10 Hz, 2H), 6.62 (d, J = 8.0 Hz, 2H), 4.40 (d, J = 9.1 Hz, 1H), 4.39 (d, J = 9.1 Hz, 1H), 3.98-3.85 (m, 4H), 3.75-3.72 (dd, J = 10.0, 5.0 Hz, 2H), 3.57-3.40 (m, 2H), 3.17-3.09 (m, 4H), 2.85 (s, 3H), 1.98-1.94 (m, 2H), 1.53-1.49 (m, 2H), 1.46 (s, 2H), 1.07 (s, 6H), 0.45 (s, 9H).13C NMR (126 MHz, D2O) δ 171.03, 155.30, 144.10, 135.23, 133.44, 132.91, 130.30, 129.19, 127.71, 126.57, 117.86, 117.17, 113.63, 78.42, 69.49, 69.26, 67.09, 64.28, 60.66, 56.00, 47.98, 37.38, 31.37, 31.01, 30.65, 23.08, 20.70, 18.89. HRMS m / z: [M-HCOO]+calcd. for C49H63NO4P+: 760.4490, found 760.4514. Experimental procedure for the preparation of JHSW-19 N-(4-((9-Azidononyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium. To a solution of sodium azide (1mmol) in acetone / water (3 / 1, 4.8mL) was added JHSW-m-06 (1 mmol). The reaction mixture was stirred for 3 h at 23 °C. Then, 0.5 ml water was added and the solution was extracted with dichloromethane (3×2 mL). The organic layers were dried over anhydrous Na2SO4and filtered and the solvent was concentrated in vacuo. The residue was purified by column chromatography (silica gel, MeCN / dichloromethane, 2 / 1) to give the desired product as a colorless oil (67% yield). 1H NMR (400 MHz, CD3CN) δ 7.42 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.48 (s, 2H), 4.12-4.10 (m, 2H), 4.00-3.95 (m, 4H), 3.84-3.82 (m, 2H), 3.47-3.45 (m, 2H), 2.97 (s, 6H), 1.83-1.69 (m, 6H), 1.57-1.31 (m, 12H), 1.30 (s, 6H), 0.67 (s, 9H). HRMS m / z: [M-Br+H]+calcd. for C36H60N4O3+: 596.4660, found 596.4648. N,N-Dimethyl-N-(4-((9-(4-((2-(2-(5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4- yl)nonyl)oxy)benzyl)-2-(2-(4-(2,4,4-trimethyl pentan-2-yl)phenoxy)ethoxy)ethan-1- aminium formate (JHSW-19). To a solution of N-(4-((9-azidononyl)oxy)benzyl)-N,N- dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy) ethan-aminium bromide (0.15 mmol) in water (10 mL), a solution of 5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4- d]imidazol-4-yl)-N-(2-(2-(prop-2-yn-1-yloxy)ethoxy)ethyl)pentanamide (0.2 mmol) in methanol (10 mL) was added. Then, TBTA (0.01 mmol), copper (II) sulfate pentahydrate (0.01 mmol), and ascorbic acid (0.02 mmol) were added. The reaction mixture was stirred at 23 °C for 2 h. The solvent was removed under vacuum. The residue was purified by HPLC (0.1% formic acid in water, 0.1% formic acid in MeCN), and part of the solvent was removed in vacuo. Then the remaining solvent was removed under freeze-drying conditions to give JHSW-19 as a white solid (49% yield). 1H NMR (400 MHz, D2O) δ 8.31 (s, 1H), 7.71 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.63 (d, J = 8.0 Hz, 4H), 4.46 (s, 2H), 4.37-4.31 (m, 3H), 4.19-4.16 (m, 1H), 4.07-4.04 (m, 2H), 3.92-3.87 (m, 4H), 3.71-3.67 (m, 4H), 3.50-3.45 (m, 4H), 3.37 (t, J = 4.0 Hz, 2H), 3.25 (m, 2H), 3.16 (t, J = 4.0 Hz, 2H), 2.99-2.94 (m, 1H), 2.87 (s, 6H), 2.70-2.66 (m, 1H), 2.48-2.44 (m, 1H), 1.97 (t, J = 8.0 Hz, 2H), 1.55-1.44 (m, 7H), 1.36-1.22 (m, 4H), 1.17-1.10 (m, 10H), 1.02-0.97 (m, 9H), 0.54 (s, 9H).13C NMR (126 MHz, D2O) δ 175.78, 170.87, 165.13, 160.28, 156.36, 144.14, 141.69, 134.84, 126.88, 124.14, 119.57, 114.71, 113.82, 69.52, 69.45, 69.14, 68.90, 68.03, 67.83, 67.01, 64.61, 63.31, 61.81, 61.45, 61.33, 60.17, 56.87, 55.25, 50.61, 50.03, 39.88, 38.87, 37.69, 35.38, 32.13, 31.87, 31.69, 29.75, 28.97, 28.89, 28.61, 27.96, 27.78, 26.01, 25.69, 25.27. HRMS m / z: [M-HCOO]+calcd. for C53H86N7O7S+: 964.6304, found 964.6423. Experimental procedure for the preparation of JHSW-20 N,N-Diethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethan-1-amine (23). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethan-1-amine (2), compound 23 was prepared from 2- (4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethanol (1, 2 mmol) and 2-chloro-N,N- diethylethanamine chloride (4 mmol) to give 23 as a red liquid (77% yield).1H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 4.09- 4.06 (m, 2H), 3.80-3.74 (m, 4H), 3.37-3.33 (m, 2H), 2.79-2.74 (m, 4H), 1.67 (s, 2H), 1.31 (s, 6H), 1.12 (t, J = 8.0 Hz, 6H), 0.68 (s, 9H). HRMS m / z: [M+H]+calcd. for C22H40NO2+: 350.3059, found 350.3071. N-(4-(4-Bromobutoxy)benzyl)-N,N-diethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (24). Following the procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04), reaction of 23 gave 24 as a light yellow oil (73% yield). 1H NMR (500 MHz, CDCl3) δ 7.31 (m, 1H ), 7.25-7.22 (m, 3H), 7.07 (d, J = 5.0 Hz, 2H), 6.98-6.96 (m, 2H), 6.76 (d, J = 10.0 Hz, 2H), 4.79 (s, 2H), 4.13-4.09 (m, 2H), 4.03 (t, J = 5.0 Hz, 2H), 3.94-3.92 (m, 2H), 3.85-3.83 (m, 2H), 3.59-3.55 (m, 2H), 3.51-3.47 (m, 4H), 2.07- 2.04 (m, 2H), 1.96-1.92 (m, 2H), 1.68 (s, 2H), 1.47 (t, J = 5.0 Hz, 6H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 159.46, 156.03, 142.97, 130.42, 127.27, 119.26, 116.74, 113.57, 70.08, 67.38, 66.87, 65.09, 63.22, 56.94, 54.25, 47.65, 37.98, 33.51, 32.33, 31.77, 29.41, 27.79, 8.89, 8.77. HRMS m / z: [M-Br]+calcd. for C33H53NO3Br+: 590.3204, found 590.3262. (4-(4-((Diethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)triphenylphosphonium diformate (JHSW-20). Following the procedure for the preparation of JHSW-01, compound JHSW-20 was prepared from N-(4-(4-bromobutoxy)benzyl)-N,N-diethyl-2-(2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethoxy)ethan-1-aminium bromide (24, 0.25 mmol) and triphenyl-phosphine (1 mmol) to give JHSW-20 as a colorless oil (45% yield). 1H NMR (400 MHz, D2O) δ 8.22 (s, 2H), 7.61-7.57 (m, 3H), 7.48-7.38 (m, 12H), 7.09 (t J = 8.0 Hz, 1H), 6.96-6.86 (m, 4H), 6.72 (d, J = 8.0 Hz, 1H), 6.56 (d, J = 8.0 Hz, 2H), 4.22 (s, 2H), 3.95 (m, 2H), 3.84-3.81 (m, 4H), 3.68 (m, 2H), 3.20-3.07 (m, 8H), 1.76-1.73 (m, 2H), 1.62-1.57 (m, 2H), 1.27 (s, 2H), 1.14 (t, J = 8.0 Hz, 2H), 0.88 (s, 6H), 0.29 (s, 9H).13C NMR (126 MHz, D2O) δ 169.42, 158.34, 155.93, 135.09, 133.32, 130.11, 128.76, 127.07, 118.85, 118.23, 117.37, 116.78, 113.87, 69.54, 67.18, 66.66, 64.28, 62.43, 56.30, 55.79, 53.32, 37.40, 36.65, 31.66, 31.40, 31.24, 29.01, 18.88, 7.19. HRMS m / z: [M-HCOO]+calcd. for C52H69NO5P+: 818.4908, found 818.5043. Experimental procedure for the preparation of JHSW-21 N-Benzyl-N-(4-(4-bromobutoxy)benzyl)-N-methyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethan-1-aminium bromide (JHSW-m-13). Following the procedure for the preparation of JHSW-04, JHSW-m-13 was prepared from N-benzyl-N-methyl-2-(2-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)-ethoxy)ethan-1-amine (22, 0.5 mmol) and 1-(4- bromobutoxy)-4-(bromomethyl)benzene (0.75 mmol) to give JHSW-m-13 as a light yellow oil (75% yield). 1H NMR (400 MHz, CD3CN) δ 7.55-7.51 (m, 3H), 7.50-7.45 (m, 4H), 7.26 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 12.0 Hz, 2H), 6.79 (d, J = 12.0 Hz, 2H, 4.67-4.62 (m, 2H), 4.59-4.56 (m, 2H), 4.15-4.13 (m, 2H), 4.04-4.01 (m, 2H), 3.99-3.98 (m, 2H), 3.87-3.85 (m, 2H), 3.54-3.51 (m, 2H), 3.41-3.38 (m, 2H), 2.86 (s, 3H), 2.02-1.98 (m, 2H), 1.90-1.86 (m, 2H), 1.69 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.63, 156.40, 142.46, 135.02, 133.52, 130.50, 129.07, 127.28, 120.70, 119.27, 114.87, 113.62, 69.64, 67.26, 66.92, 66.32, 66.18, 64.40, 56.71, 56.40, 53.97, 43.55, 37.63, 33.88, 31.85, 31.05, 29.28, 27.51. HRMS m / z: [M-Br]+calcd. for C37H53NO3Br+: 640.3183, found 640.3191. (4-(4-((Benzyl(methyl)(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl) phenoxy)butyl)triphenylphosphonium diformate (JHSW-21). Following the procedure for the preparation of JHSW-01, JHSW-21 was prepared from JHSW-m-13 (0.25 mmol) and triphenyl-phosphine (1 mmol) to give JHSW-21 as a colorless oil (30% yield). 1H NMR (400 MHz, D2O) δ 8.26 (s, 2H), 7.75-7.69 (m, 3H), 7.60-7.48 (m, 17H), 7.26 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.79-6.77 (m, 2H), 6.69-6.68 (m, 2H), 4.12-4.11 (m, 4H), 3.99 (t, J = 4.0 Hz, 2H), 3.92-3.90 (m, 4H), 3.79-3.77 (m, 2H), 3.32-3.29 (m, 2H), 3.21-3.14 (m, 2H), 2.71 (s, 3H), 1.87-1.82 (m, 2H), 1.77-1.71 (m, 2H), 1.36 (s, 2H), 0.97 (s, 6H), 0.33 (s, 9H).13C NMR (126 MHz, D2O) δ 169.08, 156.40, 154.65, 144.15, 140.75, 136.78, 133.67, 131.86, 130.21, 126.84, 123.88, 120.57, 119.11, 117.46, 114.33, 113.75, 113.07, 71.94, 69.70, 67.96, 67.65, 65.04, 62.77, 58.64, 53.70, 51.08, 37.60, 35.87, 32.39, 31.40, 28.93, 26.79, 23.67. HRMS m / z: [M-HCOO]+calcd. for C56H69NO5P+: 866.4908, found 866.4978. Experimental procedure for the preparation of JHSW-22 2-Phenoxyethanol (25). Following the procedure for the preparation of 2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethan-1-ol (1), compound 25 was prepared from phenol (0.05 mmol) and 2-bromoethanol (0.1 mol) to give 25 as a colorless oil (82% isolated yield). N,N-Dimethyl-2-(2-phenoxyethoxy)ethan-1-amine (26). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethan-1- amine (2), compound 25 gave 26 as a red liquid (73% yield).1H NMR (500 MHz, CDCl3) δ 7.27-7.23 (m, 2H), 6.94-6.89 (m, 3H), 4.12 (t, J = 5.0 Hz, 2H), 3.81 (t, J = 5.0 Hz, 2H), 3.64 (t, J = 5.0 Hz, 2H), 2.53 (t, J = 5.0 Hz, 2H), 2.26 (s, 6H).13C NMR (126 MHz, CDCl3) δ 158.74, 129.44, 120.88, 114.62, 69.55, 69.43, 67.30, 58.82, 45.82. HRMS m / z: [M+H]+calcd. for C12H20NO2+: 210.1494, found 210.1512. N-(4-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-phenoxyethoxy)ethan-1-aminium bromide (JHSW-m-14). Following the procedure for the preparation of N-(4-(4- bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04), 26 and 4 reacted to give JHSW- m-14 as a light yellow oil (77% yield).1H NMR (400 MHz, CD3CN) δ 7.40-7.37 (m, 1H), 7.30-7.27 (m, 2H), 7.13-7.06 (m, 3H), 6.96-6.91 (m, 3H), 4.55 (s, 2H), 4.17-4.15 (m, 2H), 4.05- 4.02 (m, 2H), 4.02-3.99 (m, 2H), 3.88-3.86 (m, 2H), 3.56-3.53 (m, 4H), 3.05 (s, 6H), 2.03-1.98 (m, 2H), 1.91-1.87 (m, 2H).13C NMR (100 MHz, CD3CN) δ159.23, 158.73, 130.17, 129.61, 125.34, 120.92, 119.22, 114.49, 69.48, 68.56, 67.23, 66.95, 64.48, 63.25, 50.56, 33.96, 29.31, 27.51. HRMS m / z: [M-Br]+calcd. for C23H33NO3Br+: 452.1618, found 456.1626. (4-(4-((Dimethyl(2-(2- phenoxyethoxy)ethyl)ammonio)methyl)phenoxy)butyl)triphenylphosphonium diformate (JHSW-22). Following the procedure for the preparation of JHSW-01, compound JHSW-22 was prepared from JHSW-m-14 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-22 as a white solid (44% yield). 1H NMR (400 MHz, D2O) δ 8.25 (s, 2H), 7.69-7.65 (m, 3H), 7.52-7.46 (m, 12H), 7.24 (t, J = 8.0 Hz, 1H), 7.04-6.96 (m, 3H), 6.88-6.86 (m, 2H), 6.73-6.67 (m, 3H), 4.35 (s, 2H), 4.06 -4.04 (m, 2H), 3.91 -3.88 (m, 4H), 3.76-3.74 (m, 2H), 3.39 -3.37 (m, 2H), 3.13-3.05 (m, 2H), 2.90 (s, 6H), 1.77-1.74 (m, 2H), 1.64-1.58 (m, 2H).13C NMR (126 MHz, D2O) δ 169.94, 157.82, 134.96, 133.34, 130.05, 128.64, 125.94, 121.54, 119.22, 118.21, 117.52, 116.79, 114.68, 69.31, 68.58, 67.09, 66.83, 64.38, 62.55, 50.71, 28.72, 20.63, 18.53. HRMS m / z: [M- HCOO]+calcd. for C42H49NO5P+: 678.3343, found 678.3435. Experimental procedure for the preparation of JHSW-23 2-(2,4-Di-tert-butylphenoxy)ethanol (27). Following the procedure of preparation of 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethan-1-ol (1), compound 27 was prepared from 2,4-di-tert-butylphenol (0.05 mmol) and 2-bromoethanol (0.1 mol) to give 27 as a colorless oil (72% yield). 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.0 Hz, 1H), 7.17-7.15 (dd, J = 8.0, 2.5 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 3.99-3.96 (m, 2H), 3.83-3.79 (m, 2H), 1.62-1.58 (m, 2H), 1.40 (s, 9H), 1.30 (s, 9H). HRMS m / z: [M+H]+calcd. For C16H27O2+: 251.2011, found 251.2042. 2-(2-(2,4-Di-tert-butylphenoxy)ethoxy)-N,N-dimethylethan-1-amine (28). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-amine (2), compound 27 was reacted to give 28 as a light yellow liquid (81% yield).1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 4.0 Hz, 1H), 7.17-7.15 (dd, J =8.0, 4.0 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 4.13 (t, J = 8.0 Hz, 2H), 3.86 (t, J = 4.0 Hz, 2H), 3.66 (t, J = 8.0 Hz, 2H), 2.56 (t, J = 8.0 Hz, 2H), 2.30 (s, 6H), 1.39 (s, 9H), 1.30 (s, 9H).13C NMR (126 MHz, CDCl3) δ 155.30, 142.63, 137.34, 123.91, 123.29, 111.41, 69.87, 69.37, 67.01, 58.91, 45.87, 35.07, 34.27, 31.62, 29.90. HRMS m / z: [M+H]+calcd. for C20H36NO2+: 322.2746, found 322.2762. N-(4-(4-Bromobutoxy)benzyl)-2-(2-(2,4-di-tert-butylphenoxy)ethoxy)-N,N- dimethylethan-1-aminium bromide (JHSW-m-15). Following the procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04), reaction of 28 and 4 gave JHSW-m-15 as a light yellow oil (89% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.36 (t, J = 8.0 Hz, 1H), 7.16 (d, J = 6.0 Hz, 1H), 7.11-7.06 (m, 4H), 6.83 (d, J = 8.0 Hz, 1H), 4.51 (s, 2H), 4.10-4.08 (m, 2H), 4.01-3.96 (m, 4H), 3.84-3.82 (m, 2H), 3.58-3.55 (m, 2H), 3.51 (m, 2H), 2.96 (s, 6H), 1.95-1.90 (m, 2H), 1.83- 1.77 (m, 2H), 1.27 (s, 9H), 1.20 (s, 9H).13C NMR (100 MHz, DMSO-d6) δ 159.05, 155.37, 142.50, 136.78, 130.47, 129.78, 125.63, 123.90, 119.70, 112.54, 69.76, 67.90, 67.23, 64.39, 63.38, 62.77, 50.41, 35.26, 35.03, 34.36, 31.88, 30.19, 29.53, 27.76. HRMS m / z: [M-Br]+calcd. for C31H49NO3Br+: 564.2870, found 564.2882. (4-(4-(((2-(2-(2,4-Di-tert- butylphenoxy)ethoxy)ethyl)dimethylammonio)methyl)phenoxy)butyl)triphenyl phosphonium diformate (JHSW-23). Following the procedure for the preparation of JHSW- 01, JHSW-23 was prepared from JHSW-m-15 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-23 as a white solid (49% isolated yield). 1H NMR (500 MHz, D2O) δ 8.21 (s, 2H), 7.62-7.58 (m, 3H), 7.50-7.45 (m, 6H), 7.43- 7.38 (m, 6H), 7.19 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 1.0 Hz, 1H), 6.97-6.90 (m, 2H), 6.84-6.81 (m, 2H), 6.67 (d, J = 8.0 Hz, 1H), 4.34 (s, 2H), 3.96-3.92 (m, 4H), 3.90-3.87 (m, 2H), 3.78- 3.76 (m, 2H), 3.41 (m, 2H), 3.17-3.09 (m, 2H), 2.90 (s, 6H), 1.77-1.73 (m, 2H), 1.66-1.61 (m, 2H), 0.96 (s, 9H), 0.92 (s, 9H).13C NMR (126 MHz, D2O) δ 168.73, 158.20, 155.00, 143.47, 137.58, 135.04, 133.32, 130.14, 128.60, 125.91, 123.84, 118.97, 118.16, 117.47, 113.04, 70.07, 68.88, 67.37, 66.73, 64.37, 62.88, 50.61, 34.39, 33.61, 30.78, 29.22, 28.85, 21.08, 18.85. HRMS m / z: [M-HCOO]+calcd. for C50H65NO5P+: 790.4595, found 790.4627. Experimental procedure for the preparation of JHSW-24 2-((5,6,7,8-Tetrahydronaphthalen-2-yl)oxy)ethanol (29). Following the procedure for the preparation of 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethan-1-ol (1), compound 29 was prepared from 5,6,7,8-tetra-hydronaphthalen-2-ol (0.05 mmol) and 2-bromoethanol (0.1 mol) to give 29 as a colorless oil (75% yield). 1H NMR (400 MHz, CDCl3) δ 6.96 (d, J = 8.0 Hz, 1H), 6.70-6.67 (dd, J = 8.0, 4.0 Hz, 1H), 6.63-6.62 (d, J = 4.0Hz, 1H), 4.05-4.03 (m, 2H), 3.94-3.91 (m, 2H), 2.75-2.68 (m, 4H), 1.80-1.75 (m, 4H). HRMS m / z: [M+H]+calcd. for C12H17O2+: 193.1229, found 193.1261. N,N-Dimethyl-2-(2-((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)ethoxy)ethan-1-amine (30). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2), compound 29 gave 30 as a light yellow liquid (82% yield). 1H NMR (400 MHz, CDCl3) δ 6.93 (d, J = 8.0 Hz, 1H), 6.68-6.65 (dd, J = 8.0, 4.0 Hz, 1H), 6.61 (d, J = 4.0 Hz, 1H), 4.08 (t, J = 8.0 Hz, 2H), 3.65 (t, J = 8.0 Hz, 2H), 2.73-2.66 (m, 4H), 2.53 (t, J = 8.0 Hz, 2H), 2.27 (s, 6H), 1.77-1.74 (m, 4H). HRMS m / z: [M+H]+calcd. for C16H26NO2+: 264.1964, found 264.2022. N-(4-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-((5,6,7,8-tetrahydronaphthalen-2- yl)oxy)ethoxy)-ethan -1-aminium bromide (31). Following the procedure for the preparation of N-(4-(4-bromobutoxy)-benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04), compound 30 gave 31 as a light yellow oil (81% yield). 1H NMR (400 MHz, CD3CN) δ 7.47 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 1H), 6.64-6.58 (m, 2H), 4.60 (s, 2H), 4.09-4.07 (m, 2H), 4.01 (t, J = 8.0 Hz, 2H), 3.98-3.96 (m, 2H), 3.83-3.80 (m, 2H), 3.55-3.50 (m, 4H), 3.02 (s, 6H), 2.66-2.61 (m, 4H), 2.01-1.96 (m, 2H), 1.89-1.84 (m, 2H), 1.71-1.70 (m, 4H). HRMS m / z: [M-Br]+calcd. For C27H39NO3Br+: 504.2108, found 504.2146. (4-(4-((Dimethyl(2-(2-((5,6,7,8-tetrahydronaphthalen-2- yl)oxy)ethoxy)ethyl)ammonio)methyl)phenoxy) butyl)triphenylphosphonium diformate (JHSW-24). Following the procedure for the preparation of JHSW-01, JHSW-24 was prepared from 31 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-24 as a white solid (46% yield). 1H NMR (400 MHz, D2O) δ 8.21 (s, 2H), 7.62-7.61 (m, 3H), 7.45-7.42 (m, 12H), 7.16 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 8.0 Hz, 2H), 6.49 (t, J = 8.0 Hz, 2H), 6.42-6.30 (m, 1H), 4.19 (s, 2H), 3.99-3.96 (m, 2H), 3.88-3.82 (m, 4H), 3.70 (m, 2H), 3.36-3.31 (m, 2H), 3.12-3.02 (m, 2H), 2.81 (s, 6H), 2.16-2.10 (m, 4H), 1.77-1.70 (m, 2H), 1.63-1.55 (m, 2H), 1.20-1.19 (m, 4H).13C NMR (126 MHz, D2O) δ 169.08, 159.59, 155.70, 138.50, 135.06, 134.65, 133.22, 130.02, 128.70, 125.90, 119.75, 118.22, 117.35, 114.84, 112.25, 69.56, 68.17, 67.10, 66.57, 64.40, 62.30, 50.21, 28.85, 28.59, 27.82, 22.68, 22.41, 21.03, 18.61. HRMS m / z: [M-HCOO]+calcd. for C46H55NO5P+: 732.3813, found 732.3842. Experimental procedure for the preparation of JHSW-25 2-(3,4,5-Tris(benzyloxy)phenoxy)ethanol (32). Following the procedure for the preparation of 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethanol (1), compound 32 was prepared from 3,4,5-tris(benzyloxy) phenol (0.05 mmol) and 2-bromoethanol (0.1 mol) to give 32 as a colorless oil (72% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.44-7.30 (m, 15H), 6.69-6.62 (m, 2H), 5.10 (s, 2H), 5.07 (s, 4H), 4.47 (s, 1H), 4.01 (t, J = 5.0 Hz, 2H), 3.83-3.79 (m, 2H). HRMS m / z: [M+H]+calcd. for C29H29O5+: 457.2015, found 457.2031. N,N-Dimethyl-2-(2-(3,4,5-tris(benzyloxy)phenoxy)ethoxy)ethanamine (33). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethoxy)ethanamine (2) compound 32 gave 33 as a light yellow liquid (87% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.43-7.29 (m, 15H), 6.70-6.67 (m, 1H), 6.57-6.55 (m, 1H), 5.07 (br, 6H), 4.06-4.04 (m, 2H), 3.97-3.91 (m, 4H), 3.80-3.78 (m, 2H). HRMS m / z: [M+H]+calcd. for C33H38NO5+: 528.2750, found 528.2762. N-(4-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(3,4,5- tris(benzyloxy)phenoxy)ethoxy)ethan-1-aminium bromide (34). Following the procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04), compound 33 gave 34 as a light yellow oil (80% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.41-7.28 (m, 17H), 6.81 (d, J = 10.0 Hz, 2H), 6.66 (d, J = 10.0 Hz, 1H), 6.55 (d, J = 10.0 Hz, 1H), 5.05 (s, 2H), 5.03 (s, 2H), 4.97 (s, 2H), 4.69 (s, 2H) 4.08-4.06 (m, 2H), 3.98 (br, 2H), 3.92 (t, J = 10.0 Hz, 2H), 3.84-3.82 (m, 4H), 3.45 (t, J = 10.0 Hz, 2H), 3.02 (s, 6H), 2.04-2.01 (m, 2H), 1.94-1.90 (m, 2H). HRMS m / z: [M-Br]+calcd. for C44H51NO6Br+: 768.2895, found 768.2913. (4-(4-((Dimethyl(2-(2-(3,4,5- tris(benzyloxy)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy)butyl) triphenylphosphonium diformate (JHSW-25). Following the procedure for the preparation of JHSW-01. JHSW-25 was prepared from 34 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-25 as a white solid (42% isolated yield). 1H NMR (400 MHz, D2O) δ 8.26 (s, 2H), 7.38-7.34 (m, 3H), 7.20-7.09 (m, 12H), 6.98 (d, J = 8.0 Hz, 2H), 6.91-6.83 (m, 7H), 6.79-6.74 (m, 5H), 6.60 (m, 3H), 6.45-6.36 (m, 4H), 4.41 (s, 2H), 4.38 (s, 2H), 4.29 (s, 2H), 4.01 (s, 2H), 3.88 (m, 2H), 3.79 (m, 2H), 3.68 (m, 2H), 3.53 (m, 2H), 3.16 (m, 2H), 2.79-2.72 (m, 2H), 2.63 (s, 6H), 1.46 (m, 2H), 1.27-1.20 (m, 2H).13C NMR (126 MHz, D2O) δ 170.38, 159.60, 147.09, 146.55, 142.31, 141.96, 137.08, 134.92, 134.54, 133.03, 130.06, 128.31, 128.24, 128.07, 127.99, 127.72, 127.30, 119.48, 117.83, 117.14, 114.64, 75.08, 74.94, 70.58, 69.71, 68.01, 66.16, 64.53, 62.33, 50.09, 28.56, 24.07, 20.73. HRMS m / z: [M-HCOO]+calcd. for C63H67NO8P+: 996.4599, found 996.4625. Experimental procedure for the preparation of JHSW-26 (4-(4-Bromobutoxy)benzyl)triphenylphosphonium bromide (JHSW-m-16). 1-(4- Bromobutoxy)-4-(bromomethyl)benzene (4, 1mmol) and triphenylphosphine (1 mmol) were dissolved in toluene (7 mL). The reaction mixture was stirred at 45 °C for 24 h. After cooling to 23 °C, the solvent was evaporated. The residue was purified by column chromatography (silica gel, MeCN / CHCl3, 1 / 1) to give JHSW-m-16 (61% isolated yield) as a white NMR (500 MHz, CD3CN) δ 7.89-7.85 (m, 3H), 7.70-7.69 (m, 6H), 7.58-7.53 (m, 6H), 6.83 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 4.59 (d, J = 10.0 Hz, 2H), 3.96 (t, J = 8.0 Hz, 2H), 3.53 (t, J = 8.0 Hz, 2H), 2.00-1.97 (m, 2H), 1.88-1.84 (m, 2H).13C NMR (100 MHz, CD3CN) δ159.36, 135.24, 134.28, 132.11, 130.16, 128.95, 128.25, 114.99, 67.07, 33.94, 29.27, 28.92, 27.44. HRMS m / z: [M-Br]+calcd. for C29H29OPBr+: 505.1114, found 505.1153. (4-(4-(Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)butoxy)benzyl) triphenylphosphonium diformate (JHSW-26). Following the procedure for the preparation of JHSW-12. JHSW-26 was prepared from JHSW-m-16 (0.2 mmol) and N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanamine (2, 0.2 mmol) to give JHSW-26 as a colorless oil (37% isolated yield). 1H NMR (400 MHz, D2O) δ 8.23 (s, 2H), 7.66-7.61 (m, 3H), 7.45-7.32 (m, 12H), 6.97 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 8.0 Hz, 2H), 6.50 (d, J = 8.0 Hz, 2H), 4.42 (d, J = 16.0 Hz, 2H), 3.84 (m, 2H), 3.77 (m, 2H), 3.61-3.58 (m, 4H), 3.38 (m, 2H), 3.22- 3.18 (m, 2H), 2.92 (s, 6H), 1.70-1.62 (m, 2H), 1.41-1.38 (m, 4H), 0.97 (s, 6H), 0.38 (s, 9H)13C NMR (126 MHz, D2O) δ 169.72, 158.40, 155.77, 135.21, 133.87, 132.32, 129.93, 127.19, 118.98, 117.55, 116.86, 114.99, 113.81, 69.21, 67.09, 66.98, 64.34, 63.99, 62.42, 56.37, 51.84, 37.48, 31.73, 31.44, 31.34, 28.73, 25.14, 19.21. HRMS m / z: [M-2HCOO]2+calcd. for C50H65NO5P2+: 372.7307, found 372.7495. Experimental procedure for the preparation of JHSW-27 N,N-Dimethyl-2-(2-(4-(trifluoromethyl)phenoxy)ethoxy)ethanamine (35). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanamine (2) to give 35 as a light yellow liquid (61% isolated yield). HRMS m / z: [M+H]+calcd. for C13H19NO2F3+: 278.1368, found 278.1382. (4-(Dimethyl(2-(2-(4- (trifluoromethyl)phenoxy)ethoxy)ethyl)ammonio)butyl)triphenylphosphonium diformate (JHSW-27). Following the procedure for the preparation of JHSW-12. JHSW-27 was prepared from compound 35 (0.2 mmol) and (4-bromobutyl)triphenylphosphonium bromide (0.2 mmol) to give JHSW-27 as a light yellow oil (31% isolated yield). 1H NMR (400 MHz, D2O) δ 8.30 (s, 2H), 7.74-7.71 (m, 3H), 7.56-7.51 (m, 7H), 7.46- 7.40 (m, 5H), 7.34 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 3.98-3.96 (m, 2H), 3.85 (m, 2H), 3.74-3.72 (m, 2H), 3.47-3.45 (m, 2H), 3.30-3.25 (m, 2H), 3.10-2.98 (m, 2H), 2.98 (s, 6H), 1.90-1.82 (m, 2H), 1.47-1.41 (m, 2H).13C NMR (126 MHz, D2O) δ 171.03, 165.35, 135.15, 133.28, 130.19, 127.35 (q, J = 32.0 Hz), 121.91(q, J = 271.0 Hz), 117.75, 117.06, 114.45, 69.14, 67.18, 64.48, 63.53, 60.54, 51.94, 29.22, 22.35, 20.85. HRMS m / z: [M-HCOO]+calcd. for C36H42NO5F3P+: 640.2709, found 640.2787. Experimental procedure for the preparation of JHSW-28 (4-((8-Bromooctyl)oxy)phenyl)methanol (36). Following the procedure for the preparation of (4-(4-bromo butoxy)phenyl)methanol (3).Compound 36 was prepared from 1,8- dibromooctane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 36 as a colorless oil (90% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.60 (d, J = 8.0 Hz, 2H), 3.95 (t, J = 8.0 Hz, 2H), 3.41 (t, J = 8.0 Hz, 2H), 1.89-1.81 (m, 4H), 1.78- 1.74 (m, 2H), 1.64-1.61 (m, 1H), 1.50-1.42 (m, 6H). HRMS m / z: [M+H]+calcd. for C15H24O2Br+: 315.0960, found 315.0972. 1-(Bromomethyl)-4-((8-bromooctyl)oxy)benzene (37). Following the procedure for the preparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4) to give 37 as a colorless oil which was used for next step without further purification. N-(4-((8-Bromooctyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-08). Following the procedure for the preparation of N-(4-(4-bromo butoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) to give JHSW-m-08 as a light yellow oil (81% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 4.91 (s, 2H), 4.11-4.09 (m, 4H), 3.98-3.97 (m, 2H), 3.93 (t, J = 4.0 Hz, 2H), 3.89-3.88 (m, 2H), 3.39 (t, J = 4.0 Hz, 2H), 3.27 (s, 6H), 1.88- 1.84 (m, 2H), 1.79-1.76 (m, 2H), 1.68 (s, 2H), 1.47-1.43 (m, 4H), 1.38-1.34 (m, 4H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.00, 155.94, 143.00, 134.83, 127.28, 118.67, 115.02, 113.58, 70.03, 69.13, 68.12, 66.83, 65.42, 62.59, 56.93, 50.40, 37.98, 34.02, 32.76, 32.32, 31.78, 29.16, 28.67, 28.07, 25.91, 24.36, 19.90. HRMS m / z: [M-Br]+calcd. for C35H57NO3+: 620.3496, found 620.3480. yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) octyl)triphenylphosphonium diformate (JHSW-28). Following the procedure for the preparation of JHSW-01, JHSW-28 was prepared from JHSW-m-08 (0.25 mmol) and triphenylphosphine (1 mmol) to give as JHSW- 28 a white solid (49% isolated yield). 1H NMR (400 MHz, D2O) δ 8.22 (s, 2H), 7.62-7.59 (m, 3H), 7.48-7.43 (m, 12H), 7.22 (t, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.64-6.58 (m, 4H), 4.26 (s, 2H), 3.91 (m, 2H), 3.84 (m, 2H), 3.67 (m, 4H), 3.23 (m, 2H), 3.01-2.93 (m, 2H), 2.82 (s, 6H), 1.40-1.30 (m, 6H), 1.24-1.21 (m, 2H), 1.08-0.96 (m, 12H), 0.37 (s, 9H).13C NMR (126 MHz, D2O) δ 169.58, 160.29, 156.42, 141.55, 135.16, 133.27, 130.26, 126.85, 119.28, 118.17, 117.48, 114.77, 113.77, 67.88, 66.88, 66.72, 64.75, 59.36, 56.69, 50.19, 42.62, 37.59, 32.01, 31.76, 29.83, 28.70, 28.38, 25.33, 22.60, 21.96, 21.45, 21.04. HRMS m / z: [M-HCOO]+calcd. for C54H73NO5P+: 846.5221, found 846.5296.

[0003] Experimental procedure for the preparation of JHSW-29 (4-((10-Bromodecyl)oxy)phenyl)methanol (38). Following the procedure for the preparation of (4-(4-bromobutoxy)phenyl)methanol (3). Compound 38 was prepared from 1,10-dibromodecane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 38 as a colorless oil (89% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.60 (d, J = 8.0 Hz, 2H), 3.95 (t, J = 8.0 Hz, 2H), 3.40 (t, J = 8.0 Hz, 2H), 1.89-1.81 (m, 2H), 1.79-1.74 (m, 2H), 1.58-1.53 (m, 1H), 1.49-1.39 (m, 4H), 1.36-1.31 (m, 8H). HRMS m / z: [M+H]+calcd. for C17H28O2Br+: 343.1273, found 343.1291. 1-((10-Bromodecyl)oxy)-4-(bromomethyl)benzene (39). Following the procedure for thepreparation of 1-(4-bromobutoxy)-4-(bromomethyl)benzene (4) compound 38 gave 39 as a colorless oil which was used for next step without further purification. N-(4-((10-Bromodecyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (40). Following the procedure for the preparation of N-(4-(4-bromobutoxy)-benzyl) -N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) to give 40 as a light yellow oil (71% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.74 (d, J =8.0 Hz, 2H), 4.94 (s, 2H), 4.10-4.08 (m, 4H), 3.97-3.92 (m, 4H), 3.89-3.87 (m, 2H), 3.40 (t, J =4.0 Hz, 2H), 3.28 (s, 6H), 1.88-1.81 (m, 2H), 1.79-1.73 (m, 2H), 1.68 (s, 2H), 1.45-1.40 (m, 4H), 1.31-1.30 (m, 14H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.00, 155.97, 142.98, 134.85, 127.27, 118.74, 115.01, 113.60, 70.02, 69.04, 68.19, 66.86, 65.40, 62.52, 56.94, 50.37, 37.99, 34.08, 32.82, 32.33, 31.79, 31.66, 29.43, 29.36, 29.33, 29.13, 28.75, 28.16, 26.00. HRMS m / z: [M-Br]+calcd. for C37H61NO3Br+: 646.3830, found 646.3862. (10-(4-((dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethyl)ammonio)methyl)phenoxy) decyl)triphenylphosphonium diformate (JHSW-29). Following the procedure for the preparation of JHSW-01, JHSW-29 was prepared from compound 40 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-29 as a white solid (48% isolated yield). 1H NMR (400 MHz, D2O) δ 8.20 (s, 2H), 7.62-7.57 (m, 3H), 7.47-7.41 (m, 12H), 7.24 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.59-6.61 (m, 4H), 4.26 (s, 2H), 3.88-3.82 (m, 4H), 3.66-3.62 (m, 4H), 3.19 (br, 2H), 2.98-2.91 (m, 2H), 2.82 (s, 6H), 1.41-1.34 (m, 4H), 1.30-1.20 (m, 4H), 1.08-1.05 (m, 2H), 0.99 -0.91 (m, 14H), 0.42 (s, 9H).13C NMR (126 MHz, D2O) δ 169.48, 160.15, 156.34, 141.54, 135.15, 133.25, 130.26, 126.82, 119.64, 118.14, 117.45, 114.64, 113.83, 69.34, 67.87, 67.01, 64.48, 61.30, 56.74, 50.56, 37.57, 32.00, 31.76, 31.62, 29.92, 29.80, 28.95, 28.81, 28.62, 28.36, 25.62, 21.98, 21.47, 21.06. HRMS m / z: [M- HCOO]+calcd. for C56H77NO5P+: 874.5534, found 874.5562. Experimental procedure for the preparation of JHSW-30 (7-(4-((dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethyl)-λ4- azaneyl)methyl)phenoxy) heptyl)tri-p-tolylphosphonium diacetate (JHSW-30). Following the procedure for the preparation of JHSW-01, JHSW-30 was prepared from compound 8 (0.25 mmol) and tri-p-tolylphosphine (1 mmol). The residue was purified by HPLC (0.1% acetic acid in water, 0.1% acetic acid in acetonitrile). Part of solvent was removed in vacuo. Then the solvent remaining was removed under freeze-drying conditions to give JHSW-30 as a white solid (42% isolated yield). 1H NMR (400 MHz, D2O) δ 7.33-7.29 (m, 6H), 7.27-7.23 (m, 8H), 6.88 (d, J = 8.0 Hz, 2H), 6.65 (d, J = 8.0 Hz, 2H), 6.58 (d, J = 8.0 Hz, 2H), 4.30 (s, 2H), 3.92 (m, 2H), 3.88 (m, 2H), 3.71-3.68 (m, 4H), 3.27 (m, 2H), 2.93-2.90 (m, 2H), 2.85 (s, 6H), 2.18 (s, 9H), 1.79 (s, 6H), 1.41 (m, 2H), 1.33 (m, 4H), 1.25 (m, 2H), 1.11-1.00 (m, 4H), 0.94 (s, 6H), 0.36 (s, 9H).13C NMR (126 MHz, D2O) δ 180.76, 160.12, 156.17, 146.51, 134.73, 133.00, 130.87, 126.83, 119.55, 115.13, 114.72, 114.42, 113.82, 69.35, 68.09, 67.99, 67.04, 64.49, 61.68, 56.56, 50.39, 37.44, 31.82, 31.58, 31.44, 29.49, 29.35, 28.36, 27.75, 24.85, 22.89, 21.64, 20.99. HRMS m / z: [M-2CH3COO]2+calcd. for C55H76NO5P2+: 414.7776, found 414.7495. Experimental procedure for the preparation of JHSW-31 (7-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethyl)-λ4- azaneyl)methyl)phen-oxy)heptyl)tris(4-methoxyphenyl)phosphonium acetate (JHSW-31). Following the procedure for the preparation of JHSW-01, JHSW-31 was prepared from compound 8 (0.25 mmol) and tris(4-methoxyphenyl)phosphine (1 mmol). The residue was purified by HPLC (0.1% acetic acid in water, 0.1% acetic acid in acetonitrile). Part of solvent was removed in vacuo. Then the solvent remaining was removed under freeze-drying conditions to give JHSW-31 as a white solid (47% isolated yield). 1H NMR (500 MHz, D2O) δ 7.39-7.35 (m, 6H), 7.25 (d, J = 8.0 Hz, 2H), 6.99-6.96 (m, 6H), 6.90 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.0 Hz, 2H), 6.59 (d, J = 8.0 Hz, 2H), 4.30 (s, 2H), 3.98 (m, 2H), 3.90 (m, 2H), 3.74 (m, 4H), 3.69 (s, 9H), 3.31 (m, 2H), 2.94-2.86 (m, 8H), 1.46 (m, 2H), 1.39-1.36 (m, 2H), 1.31-1.28 (m, 4H), 1.14-1.07 (m, 4H), 0.93 (s, 6H), 0.32 (s, 9H).13C NMR (126 MHz, D2O) δ 181.41, 164.21, 160.06, 147.77, 135.22, 135.13, 134.69, 127.01, 119.56, 115.85, 115.74, 114.78, 113.79, 69.39, 68.22, 68.08, 67.06, 64.48, 56.39, 56.37, 55.72, 50.33, 37.39, 31.66, 31.38, 31.24, 31.08, 29.19, 28.16, 27.43, 24.69, 23.20, 21.43. HRMS m / z: [M-2CH3COO]2+calcd. for C55H76NO6P2+: 438.7700, found 438.7344. Experimental procedure for the preparation of JHSW-32 A procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2- (4-(2,4,4-trimethyl pentan-2-yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-04) compound 7 gave 41 as a light yellow oil (69% isolated yield). HRMS m / z: [M-Br]+calcd. For C18H31NO2Br+: 372.1533, found 372.1571. (7-(4-(((2- Hydroxyethyl)dimethylammonio)methyl)phenoxy)heptyl)triphenylphosphonium diformate (JHSW-33). Following the procedure for the preparation of JHSW-01, JHSW-33 was prepared from compound 41 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-33 as a white solid (51% isolated yield). 1H NMR (500 MHz, D2O) δ 8.31 (s, 2H), 7.74-7.71 (m, 3H), 7.65-7.54 (m, 12H), 7.33 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 4.36 (s, 2H), 3.97-3.93 (m, 4H), 3.35-3.33 (m, 2H), 3.16-3.10 (m, 2H), 2.92 (s, 6H), 1.60-1.55 (m, 4H), 1.42-1.38 (m, 2H), 1.26-1.24 (m, 4H).13C NMR (126 MHz, D2O) δ 170.56, 160.03, 134.58, 133.53, 130.00, 119.43, 118.61, 117.92, 115.06, 68.80, 68.54, 64.84, 55.29, 49.87, 29.25, 27.90, 27.18, 24.48, 21.23, 20.90. HRMS m / z: [M-HCOO]+calcd. for C37H47NO4P+: 600.3238, found 600.3300. Experimental procedure for the preparation of JHSW-33 (7-(4-((Dimethyl(2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethyl)-λ4- azaneyl)methyl)phen-oxy)butyl)triphenylphosphonium diacetate (JHSW-33). Following the procedure of preparation of JHSW-01, JHSW-33 was prepared from JHSW-m-04 (0.25 mmol) and triphenylphosphine (1 mmol). The residue was purified by HPLC (0.1% acetic acid in water, 0.1% acetic acid in acetonitrile). Part of solvent was removed in vacuo. Then the solvent remaining was removed under freeze-drying conditions to give JHSW-33 as a white solid (53% isolated yield). 1H NMR (500 MHz, D2O) δ 7.67-7.63 (m, 3H), 7.53-7.45 (m, 12H), 7.25 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 8.0 Hz, 2H), 4.29 (s, 2H), 4.03-4.01 (m, 2H), 3.92-3.89 (m, 4H), 3.75-3.74 (m, 2H), 3.35-3.33 (m, 2H), 3.18-3.12 (m, 2H), 2.85 (s, 6H), 1.80 (m, 8H), 1.67-1.63 (m, 2H), 1.28 (s, 2H), 0.90 (s, 6H), 0.29 (s, 9H).13C NMR (126 MHz, D2O) δ 180.72, 159.72, 155.71, 142.88, 135.11, 133.35, 130.21, 127.22, 119.70, 118.17, 117.48, 114.88, 113.81, 69.41, 68.25, 67.07, 66.41, 64.47, 62.25, 56.17, 50.25, 37.34, 31.53, 31.25, 31.10, 28.80, 22.84, 20.99, 18.69. HRMS m / z: [M-2CH3COO]2+calcd. for C49H64NO3P2+: 372.7307, found 372.7014. Experimental procedure for the preparation of JHSW-34 2-([1,1'-Biphenyl]-4-yloxy)ethanol (42). Following the procedure of preparation of 2- (4-(2,4,4-trimethyl-pentan-2-yl)phenoxy)ethanol (1), compound 42 was prepared from 4- phenylphenol (0.05 mmol) and 2- bromoethanol (0.1 mol) to give 42 as a white solid (68% isolated yield). 2-(2-([1,1'-Biphenyl]-4-yloxy)ethoxy)-N,N-dimethylethanamine (43). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-amine (2), compound 42 gave 43 as a light yellow liquid (67% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.55-7.48 (m, 4H), 7.40 (t, J = 8.0 Hz, 2H), 7.31-7.27 (m, 1H), 6.97 (d, J = 8.0 Hz, 2H), 4.18-4.15 (m, 2H), 3.85-3.82 (m, 2H), 3.67 (t, J = 8.0 Hz, 2H), 2.56 (t, J = 8.0 Hz, 2H), 2.29 (s, 6H). HRMS m / z: [M+H]+calcd. For C18H24NO2+: 286.1807, found 286.1831. 2-(2-([1,1'-Biphenyl]-4-yloxy)ethoxy)-N-(4-(4-bromobutoxy)benzyl)-N,N- dimethylethan-1-aminium bromide (JHSW-m-09). Following the procedure for the preparation of N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04) to give light yellow oil JHSW- m-09 (77% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.56-7.54 (m, 4H), 7.44-7.37 (m, 4H), 7.25 (t, J = 8.0 Hz, 1H), 7.00-6.97 (m, 4H), 4.50 (s, 2H), 4.16 (t, J = 4.0 Hz, 2H), 4.00-3.95 (m, 4H), 3.81 (t, J = 4.0 Hz, 2H), 3.55 (t, J = 4.0 Hz, 2H), 3.47 (t, J = 4.0 Hz, 2H), 2.95 (s, 6H), 1.95-1.88 (m, 2H), 1.83-1.76 (m, 2H).13C NMR (100 MHz, DMSO-d6) δ 160.37, 158.48, 140.21, 135.01, 133.19, 129.35, 128.25, 127.24, 126.63, 120.30, 115.39, 115.16, 69.28, 68.74, 67.64, 67.31, 67.24, 64.39, 62.74, 35.27, 29.50, 27.76.HRMS m / z: [M-Br]+calcd. For C29H37NO3+: 528.1931, found 528.1923. (4-(4-(((2-(2-([1,1'-Biphenyl]-4- yloxy)ethoxy)ethyl)dimethylammonio)methyl)phenoxy)butyl)triphenyl phosphonium bromide (JHSW-34). Following the procedure for the preparation of JHSW-01, JHSW-34 was prepared from JHSW-m-09 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-34 as a white solid (52% isolated yield). 1H NMR (400 MHz, D2O) δ 7.87-7.85 (m, 3H), 7.79-7.73 (m, 12H), 7.56-7.53 (m, 4H), 7.43-7.36 (m, 4H), 7.24 (m, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 4.50 (s, 2H), 4.17-4.15 (m, 2H), 4.02-3.96 (m, 4H), 3.83-3.11 (m, 2H), 3.68-3.60 (m, 2H), 3.47 (m, 2H), 2.94 (s, 6H), 1.90-1.85 (m, 2H), 1.69-1.64 (m, 2H).13C NMR (126 MHz, DMSO-d6) δ 162.36, 160.56, 142.23, 137.73, 137.21, 136.00, 135.41, 133.02, 131.64, 130.45, 129.55, 128.73, 122.17, 121.17, 120.49, 117.60, 71.59, 70.28, 69.49, 68.84, 66.58, 64.77, 52.34, 31.59, 22.16, 21.04. HRMS m / z: [M-2Br]2+calcd. for C47H52NO3P2+: 354.6837, found 354.6553.

[0004] Experimental procedure for the preparation of JHSW-35 3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)propan-1-ol (44). Following the procedure for the preparation of 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethan-1-ol (1). Compound 44 was prepared from 4-(2,4,4-trimethylpentan-2-yl)phenol (0.05 mmol) and 3-bromo-1-propanol (0.1 mol) to give 44 as a white solid (63% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.26 (d, J = 8.0 Hz, 2H), 6.81 (d, J = 8.0 Hz, 2H), 4.11 (t, J = 5.0 Hz, 2H), 3.88-3.85 (m, 2H), 2.06-2.01 (m, 2H), 1.97 (m, 1H), 1.70 (s, 2H), 1.34 (s, 6H), 0.72 (s, 9H). HRMS m / z: [M+H]+calcd. For C17H29O2+: 265.2168, found 265.2194. N,N-Dimethyl-2-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propoxy)ethanamine (45). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2), compound 44 gave 45 as a light yellow liquid (61% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.21 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.0 Hz, 2H), 4.00 (t, J = 5.0 Hz, 2H), 3.61-3.54 (m, 4H), 3.37-3.33 (m, 2H), 2.56 (t, J = 5.0 Hz, 2H), 2.29 (s, 6H), 2.04-1.99 (m, 2H), 1.65 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (126 MHz, CDCl3) δ 156.58, 142.13, 127.02, 113.64, 68.64, 67.82, 64.70, 59.06, 58.63, 56.97, 45.61, 37.91, 31.76, 24.19, 13.71. HRMS m / z: [M+H]+calcd. For C21H38NO2+: 336.2903, found 336.3981. N-(4-(4-Bromobutoxy)benzyl)-N,N-dimethyl-2-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)propoxy) ethanaminium bromide (JHSW-m-10). Following the procedure for the preparation of N-(4-(4-bromo butoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-04), compound 45 gave JHSW-m- 10 as a light yellow oil (80% isolated yield). 1H NMR (500 MHz, CD3CN) δ 7.47-7.43 (m, 2H), 7.30-7.26 (m, 2H), 7.01-6.97 (m, 2H), 6.82-6.79 (m, 2H), 4.50 (s, 2H), 4.07-4.01 (m, 4H), 3.89-3.86 (m, 2H), 3.70-3.65 (m, 2H), 3.57-3.53 (m, 2H), 3.50-3.46 (m, 2H), 2.96 (s, 6H), 2.04-2.01 (m, 4H), 1.92-1.89 (m, 2H), 1.72- 1.70 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (126 MHz, CD3CN) δ 160.70, 156.64, 142.13, 134.68, 127.23, 119.41, 114.85, 113.58, 68.35, 67.68, 67.20, 64.61, 64.12, 63.00, 56.41, 49.97, 37.62, 33.91, 31.87, 31.11, 31.05, 29.29, 29.10, 27.51. HRMS m / z: [M-Br]+calcd. for C32H51NO3Br+: 578.3027, found 578.3021. (4-(4-((Dimethyl(2-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)propoxy)ethyl)ammonio)methyl)phen-oxy)butyl)triphenylphosphonium diformate (JHSW-35). Following the procedure for the preparation of JHSW-01, JHSW-34 was prepared from JHSW-m-10 (0.25 mmol) and triphenylphosphine (1 mmol) to give JHSW-34 as a white solid (42% isolated yield). 1H NMR (500 MHz, D2O) δ 8.28 (s, 2H), 7.68-7.64 (m, 3H), 7.55-7.46 (m, 12H), 7.20 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.56 (d, J = 8.0 Hz, 2H), 4.25 (s, 2H), 3.91 (t, J = 5.0 Hz, 2H), 3.86-3.82 (m, 4H), 3.57 (t, J = 5.0 Hz, 2H), 3.35-3.34 (m, 2H), 3.23-3.15 (m, 2H), 2.75 (s, 6H), 1.86-1.80 (m, 4H), 1.70-1.65 (m, 2H), 1.28 (s, 2H), 0.91 (s, 6H), 0.28 (s, 9H).13C NMR (126 MHz, D2O) δ 170.07, 159.80, 155.88, 142.46, 135.10, 133.37, 130.22, 127.12, 119.50, 118.21, 117.52, 114.91, 113.67, 68.21, 67.31, 66.52, 64.95, 64.20, 62.74, 56.21, 49.93, 37.33, 31.58, 31.28, 30.19, 28.39, 21.07, 20.66, 18.80. HRMS m / z: [M-2HCOO]2+calcd. for C50H66NO3P2+: 379.7385, found 379.7482. Experimental procedure for the preparation of JHSW-m-01 N-(4-((Tert-butoxycarbonyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium bromide (JHSW-m-01). To liquid N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2, 0.5 mmol) was added 4-(bromomethyl)phenyl tert-butyl carbonate (0.75mmol) in anhydrous dichloromethane (4 mL). After being stirred at 23 °C for 8h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, acetonitrile / dichloromethane, 1 / 1) to give JHSW-m-01 as a white solid (89% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.58 (d, J = 8.0 Hz, 2H), 7.29-7.24 (m, 4H), 6.79 (d, J = 8.0 Hz, 2H), 4.58 (s, 2H), 4.13-4.11 (m, 2H), 4.00-3.96 (m, 2H), 3.85-3.83 (m, 2H), 3.52- 3.49 (m, 2H), 3.02 (s, 6H), 1.79 (s, 2H), 1.50 (s, 9H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 156.40, 152.79, 151.35, 142.42, 134.70, 127.30, 125.37, 122.03, 113.63, 83.81, 69.53, 67.51, 66.94, 64.50, 62.94, 56.41, 50.30, 37.64, 31.87, 31.09, 31.06, 26.83. HRMS m / z: [M-Br]+calcd. for C32H50NO5+: 528.3684, found 528.3698. Experimental procedure for the preparation of JHSW-m-02 N-(4-hydroxybenzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethan-1-aminium bromide (JHSW-m-02). JHSW-m-01 (0.25 mmol) was dissolved in dichloromethane (7.5 mL), the mixture was cooled to 0°C, and then 2,2,2- trifluoroacetic acid (2.5 mL) was added to the mixture. The reaction mixture was stirred for 30 min until the starting material was completely consumed and then the mixture was concentrated in vacuo to give JHSW-m-01 as a light yellow liquid (92% isolated yield). 1H NMR (400 MHz, CDCl3) δ 8.80 (s, 1H), 7.27-7.16 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 4.41 (s, 2H), 4.11-4.09 (m, 2H), 4.00 (m, 2H), 3.86-3.84 (m, 2H), 3.51 (m, 2H), 3.00 (s, 6H), 1.68 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 159.17, 156.38, 142.46, 134.73, 127.29, 118.26, 115.83, 113.63, 69.55, 68.94, 66.93, 64.44, 62.78, 56.42, 50.06, 43.00, 37.64, 31.86, 31.09. HRMS m / z: [M- Br]+calcd. For C27H42NO3+: 428.3160, found 428.3186. Experimental procedure for the preparation of JHSW-m-03 N-(4-(4-Hydroxybutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-03). Following the procedure for the preparation of JHSW-m-01, JHSW-m-03 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethanamine (2) (0.5 mmol), and 4-(4- (bromomethyl)phenoxy)butan-1-ol (0.75 mmol) to give JHSW-m-03 as a light yellow oil (70% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.95 (s, 2H), 4.10-4.09 (m, 4H), 4.00-3.96 (m, 4H), 3.89-3.87 (m, 2H), 3.61 (t, J = 5.0 Hz, 2H), 3.29 (s, 6H), 2.00-1.94 (m, 4H), 1.68 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (126 MHz, CDCl3) δ 160.72, 155.95, 143.00, 134.89, 127.27, 119.01, 114.99, 113.57, 70.02, 68.94, 67.19, 66.83, 65.36, 62.51, 56.93, 53.45, 50.35, 37.98, 32.32, 31.78, 31.65, 29.22, 26.52. HRMS m / z: [M-Br]+calcd. for C31H50NO4+: 500.3735, found 500.3787. Experimental procedure for the preparation of JHSW-m-05 (4-(4-(Hydroxymethyl)phenoxy)butyl)triphenylphosphonium bromide (JHSW-m- 05).4-(hydroxy-methyl)phenol (4 mmol) and K2CO3 (4 mmol) were added to a solution of (4- bromobutyl)triphenyl-phosphonium bromide (3 mmol) in acetonitrile (25 mL). After heating 16 h under refluxing conditions, the reaction mixture was cooled to 23 °C. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, acetonitrile / CDCl3, 2 / 1) to give JHSW-m-05 as a white solid (69% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.89-7.84 (m, 3H), 7.80-7.76 (m, 4H), 7.75-7.70 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.0 Hz, 2H), 4.98 (t, J = 8.0 Hz, 1H), 4.35 (d, J = 8.0 Hz, 2H), 3.99-3.95 (m, 2H), 3.67-3.59 (m, 2H), 1.90-1.83 (m, 2H), 1.69-1.63 (m, 2H).13C NMR (100 MHz, DMSO-d6) δ 157.73, 135.42, 134.12, 130.79, 128.51, 128.35, 119.38, 114.55, 66.38, 62.97, 29.74, 19.96, 18.98. HRMS m / z: [M-Br]+calcd. for C29H30O2P+: 441.1978, found 441.1998. Experimental procedure for the preparation of JHSW-m-07 N,N-Dimethyl-N-(4-nitrobenzyl)-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-07). Following the procedure for the preparation of JHSW-m-01. JHSW-m-07 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2), (0.5 mmol) and 1-(bromomethyl)-4- nitrobenzene (0.75 mmol) to give JHSW-m-07 as a yellow solid (74% isolated yield). 1H NMR (400 MHz, CD3CN) δ 8.24 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.0 Hz, 2H), 4.80 (s, 2H), 4.14-4.12 (m, 2H), 4.01 (m, 2H), 3.87-3.85 (m, 2H), 3.59-3.56 (m, 2H), 3.09 (s, 6H), 1.69 (s, 2H), 1.29 (s, 6H), 0.66 (s, 9H).13C NMR (100 MHz, CD3CN) δ 156.38, 149.31, 142.47, 134.74, 134.56, 127.30, 123.86, 113.60, 69.58, 66.91, 66.74, 64.45, 63.45, 56.38, 50.70, 37.63, 31.83, 31.05, 31.0. HRMS m / z: [M-Br]+calcd. for C27H41N2O4+: 457.3061, found 457.3327. Experimental procedure for the preparation of JHSW-m-11 N,N-Dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propoxy)propan-1- amine (46). A mixture of 3-chloro-N,N-dimethylpropan-1-amine hydrochloride (30 mmol), 10M NaOH (20.6 mL), tetrabutyl ammonium bromide (TBAB, 2.4 mmol) and 3-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)propan-1-ol (12 mmol) in toluene (20.6 mL) was vigorous stirred at 80 °C for 18 h. Then the reaction mixture was cooled to 23 °C. The layers were separated, and the aqueous layers were extracted with toluene (2×20 mL). The combined organic layers were washed successively with H2O and saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 9 / 1, acetonitrile / CHCl3 / Et3N, 1 / 1 / 0.01) to give 46 as a red liquid (60% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.03 (t, J = 4.0 Hz, 2H), 3.58 (t, J = 4.0 Hz, 2H), 3.46 (t, J = 4.0 Hz, 2H), 2.02 (t, J = 4.0 Hz, 2H), 2.20 (s, 6H), 2.05-1.99 (m, 2H), 1.77-1.71 (m, 2H), 1.69 (s, 2H), 1.33 (s, 6H), 0.71 (s, 9H).13C NMR (100 MHz, CDCl3) δ156.67, 142.10, 127.02, 113.69, 69.27, 67.40, 64.77, 57.01, 56.72, 45.55, 37.94, 32.33, 31.80, 31.71, 29.83, 28.02. HRMS m / z: [M+H]+calcd. for C22H40NO2+: 350.3059, found 350.3087. N-(4-(4-bromobutoxy)benzyl)-N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)propoxy) propan-1-aminium bromide (JHSW-m-11). Following the procedure for the preparation of JHSW-m-01. JHSW-m-11 was prepared from compound 46 (0.5 mmol) and 1-(4-bromobutoxy)-4-(bromomethyl) benzene (0.75 mmol) to give JHSW-m-11 as a light yellow oil (84% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.39 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 4.33 (s, 2H), 4.03-3.98 (m, 4H), 3.58-3.48 (m, 6H), 3.27-3.23 (m, 2H), 2.86 (s, 6H), 2.03-1.96 (m, 6H), 1.90-1.86 (m, 2H), 1.70 (s, 2H), 1.30 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CD3CN) δ 156.68, 156.26, 147.24, 134.45, 129.64, 127.24, 114.89, 113.57, 68.24, 67.21, 66.69, 64.54, 60.98, 59.31, 56.40, 49.45, 35.24, 34.95, 33.88, 31.86, 31.04, 30.32, 29.28, 27.50, 23.00. HRMS m / z: [M-Br]+calcd. for C33H53NO3+: 590.3204, found 590.3153. Experimental procedure for the preparation of JHSW-m-12 N-(4-(3-Bromopropoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-12). Following the procedure for the preparation of JHSW-m-01, JHSW-m-12 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2), (0.5 mmol) and 1-(bromomethyl)-4- (3-bromopropoxy)benzene (0.75 mmol) to give JHSW-m-12 as a light yellow oil (84% isolated yield). 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 4.91 (s, 2H), 4.12-4.10 (m, 6H), 4.10-3.99 (m, 2H), 3.90-3.88 (m, 2H), 3.60 (t, J = 5.0 Hz, 2H), 3.27 (s, 6H), 2.35-2.30 (m, 2H), 1.69 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ160.61, 155.92, 143.08, 134.87, 127.31, 119.08, 115.10, 113.56, 70.05, 69.07, 68.93, 66.79, 65.42, 62.69, 56.93, 50.41, 38.00, 32.33, 32.10, 31.77, 31.65, 29.74. HRMS m / z: [M-Br]+calcd. for C31H51NO3Br+: 566.3027, found 566.3021. Experimental procedure for the preparation of JHSW-m-17 N-(4-(3-Chloropropoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-17). Following the procedure for the preparation of JHSW-m-01, JHSW-m-17 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2) (0.5mmol) and 1-(bromomethyl)-4-(3- chloropropoxy)benzene (0.75 mmol) to give JHSW-m-17 as a light yellow oil (79% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.47 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.57 (s, 2H), 4.14-4.10 (m, 4H), 3.99-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.76 (t, J = 8.0 Hz, 2H), 3.52 (t, J = 4.0 Hz, 2H), 3.01 (s, 6H), 2.23- 2.21 (m, 2H), 1.70 (s, 2H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ160.48, 156.40, 142.43, 134.80, 127.28, 119.78, 114.84, 113.63, 69.52, 68.21, 66.94, 64.62, 64.49, 62.70, 56.40, 50.04, 41.64, 37.64, 31.85, 31.79, 31.07, 31.04. HRMS m / z: [M-Br]+calcd. for C30H47NO3Cl+: 504.3239, found 504.3267. Experimental procedure for the preparation of JHSW-m-18 (4-(4-Chlorobutoxy)phenyl)methanol (47). 1,4-Dichlorobutane (12.1 mmol) and K2CO3 (16.1 mmol) were added to a solution of 4-hydroxybenzyl alcohol (6.1 mmol) in acetone (25ml). After it heated for 24 h under refluxing conditions, the reaction mixture was cooled to 23 °C. It was flitered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 6 / 1) to give 47 as a colorless oil (76% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.59 (d, J = 4.0 Hz, 2H), 3.99 (t, J = 4.0 Hz, 2H), 3.62 (t, J = 4.0 Hz, 2H), 2.00-1.92 (m, 4H). 1-(Bromomethyl)-4-(4-chlorobutoxy)benzene (48). To a cooled (0 °C) solution of (4- (4-chlorobutoxy) phenyl)methanol (47, 4 mmol) in anhydrous dichloromethane (4 mL) was added dropwise PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) under Ar. After being stirred at 23 °C for 2 h, the reaction mixture was quenched with cool H2O (4 mL), and neutralized with NaHCO3. The layers were separated, and the aqueous layers extracted with dichloromethane (2×4 mL). The combined organic layers were washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrate in vacuo. The residue was used in the next step without further purification. N-(4-(4-Chlorobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-18). Following the procedure for the preparation of JHSW-m-01, JHSW-m-18 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2), (0.5 mmol) and 1-(bromomethyl)-4- (4-chlorobutoxy)benzene (48, 0.75 mmol) to give JHSW-m-18 as a light yellow oil (79% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.44 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.95 (d, J =8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.52 (s, 2H), 4.12-4.10 (m, 2H), 4.04-4.01 (m, 2H), 3.97-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.66-3.63 (m, 2H), 3.50-3.47 (m, 2H), 2.99 (s, 6H), 1.90-1.88 (m, 4H), 1.70 (s, 2H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ160.70, 156.39, 134.74, 127.29, 119.45, 116.73, 114.83, 113.62, 69.53, 68.39, 67.33, 66.94, 64.47, 62.70, 56.40, 50.07, 44.95, 37.64, 31.85, 31.07, 31.04, 29.06, 26.27. HRMS m / z: [M- Br]+calcd. for C31H49NO3Cl+: 518.3396, found 518.3422. Experimental procedure for the preparation of JHSW-m-19 (4-((5-Chloropentyl)oxy)phenyl)methanol (49). Following the procedure for the preparation of (4-(4-chloro butoxy)phenyl)methanol (47), compound 49 was prepared from 1,5-dichloropentane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 49 as a colorless oil (71% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 4.53 (d, J = 4.0 Hz, 2H), 3.95 (t, J = 4.0 Hz, 2H), 3.56 (t, J = 4.0 Hz, 2H), 2.41 (t, J = 4.0 Hz, 1H), 1.88-1.75 (m, 4H), 1.65-1.57 (m, 2H). 1-(Bromomethyl)-4-((5-chloropentyl)oxy)benzene (50). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 50 was prepared from (4-((5-chloropentyl)-oxy)phenyl)methanol (49, 4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give light yellow oil. The residue was used in the next step without further purification. N-(4-((5-Chloropentyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethan-1-aminium bromide (JHSW-m-19). Following the procedure for the preparation of JHSW-m-01, JHSW-m-19 was prepared from N,N-dimethyl-2-(2-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2), (0.5 mmol) and 1- (bromomethyl)-4-((5-chloropentyl)oxy)benzene (50, 0.75 mmol) to give JHSW-m-19 as a light yellow oil (79% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.44 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.53 (s, 2H), 4.12-4.10 (m, 2H), 4.01-3.96 (m, 4H), 3.84-3.82 (m, 2H), 3.60 (t, J = 4.0 Hz, 2H), 3.49 (t, J = 4.0 Hz, 2H), 2.99 (s, 6H), 1.83- 1.76 (m, 4H), 1.70 (s, 2H), 1.59-1.54 (m, 2H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ160.78, 156.39, 142.44, 134.73, 127.29, 119.38, 114.81, 113.62, 69.53, 69.26, 68.37, 67.86, 66.94, 64.48, 56.40, 50.05, 45.13, 37.64, 32.03, 31.85, 31.07, 31.04, 28.09, 23.12. HRMS m / z: [M-Br]+calcd. for C32H51NO3Cl+: 532.3552, found 532.3578. Experimental procedure for the preparation of JHSW-m-20 (4-((9-Chlorononyl)oxy)phenyl)methanol (51). Following the procedure for the preparation of (4-(4-chloro butoxy)phenyl)methanol (47), compound 51 was prepared from 1,9-dichlorononane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 51 as a white solid (69% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.59 (d, J = 4.0 Hz, 2H), 3.95 (t, J = 4.0 Hz, 2H), 3.53 (t, J = 4.0 Hz, 2H), 1.81-1.73 (m, 4H), 1.67- 1.64 (m, 1H), 1.47-1.30 (m, 10H). HRMS m / z: [M+H]+calcd. for C16H26O2Cl+: 285.1621, found 285.1643. 1-(Bromomethyl)-4-((9-chlorononyl)oxy)benzene (52). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 52 was prepared from (4-((9-chlorononyl) oxy)phenyl)methanol (51) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 52 as a light yellow oil. The residue was used in the next step without further purification. N-(4-((9-Chlorononyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-20). Following the procedure for the preparation of JHSW-m-01. JHSW-m-20 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethanamine (2) (0.5 mmol) and 1-(bromomethyl)-4-((9- chlorononyl)oxy)benzene (52) (0.75 mmol) to give JHSW-m-20 as a light yellow oil (76% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.45 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.79 (d, J =8.0 Hz, 2H), 4.55 (s, 2H), 4.12-4.10 (m, 2H), 3.99-3.96 (m, 4H), 3.84-3.82 (m, 2H), 3.54 (t, J = 4.0 Hz, 2H), 3.51 (t, J = 4.0 Hz, 2H), 3.00 (s, 6H), 1.75- 1.71 (m, 4H), 1.70 (s, 2H), 1.44-1.31 (m, 8H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.84, 156.40, 142.43, 134.73, 127.28, 119.34, 114.78, 113.63, 69.53, 68.31, 68.06, 66.95, 64.49, 62.68, 56.41, 50.03, 45.29, 37.64, 32.37, 31.86, 31.08, 31.05, 29.08, 28.91, 28.80, 28.47, 26.51, 25.62. HRMS m / z: [M-Br]+calcd. for C36H59NO3Cl+: 588.4178, found 588.4186. Experimental procedure for the preparation of JHSW-m-21 (4-(3-Bromobutoxy)phenyl)methanol (53). 1,3-Dibromobutane (12.1 mmol) and K2CO3 (16.1 mmol) were added to a solution of 4-hydroxybenzyl alcohol (6.1 mmol) in acetone (25 mL). After being stirred for 6 h at 23 °C, the reaction mixture was filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 6 / 1) to give 53 as a colorless oil (52% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.60 (d, J = 4.0 Hz, 2H), 4.22-4.17 (m, 1H), 4.01-3.97 (m, 2H), 2.00-1.90 (m, 2H), 1.74 (d, J = 4.0 Hz, 3H). HRMS m / z: [M+H]+calcd. for C11H16O2Br+: 259.0334, found 259.0350. 1-(3-Bromobutoxy)-4-(bromomethyl)benzene (54). To a cooled (0 °C) solution of (4- (3-bromobutoxy) phenyl)methanol (53) (4 mmol) in anhydrous dichloromethane (4 mL) was added dropwise PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) under Ar. After being stirred at 23 °C for 0.5 h, the reaction mixture was quenched with cold H2O (4 mL) and neutralized with NaHCO3. The layers were separated, and the aqueous layers extracted with dichloromethane (2×4 mL). The combined organic layers were washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrate in vacuo. The residue was used in the next step without further purification. N-(4-(3-Bromobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-21). Following the procedure for the preparation of JHSW-m-01, JHSW-m-21 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2) (0.5 mmol) and 1-(3-bromobutoxy)- 4-(bromomethyl)benzene (54) (0.75 mmol) to give JHSW-m-21 as a light yellow oil (81% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.45 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.54 (s, 2H), 4.32-4.24 (m, 1H), 4.12-4.10 (m, 2H), 4.04-4.01 (m, 2H), 3.98-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.50 (m, 2H), 3.00 (s, 6H), 1.98- 1.95 (m, 2H), 1.71 (s, 2H), 1.69 (d, J = 4.0 Hz, 3H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.69, 156.40, 142.44, 134.74, 127.29, 119.49, 114.83, 113.63, 69.53, 68.47, 67.35, 66.94, 64.48, 62.68, 56.40, 52.08, 50.06, 37.64, 37.32, 31.85, 31.05, 27.26, 25.88. HRMS m / z: [M-Br]+calcd. for C31H49NO3Br+: 562.2891, found 562.2923. Experimental procedure for the preparation of JHSW-m-22 (4-Butoxyphenyl)methanol (55). Following the procedure for the preparation of (4-(4- chlorobutoxy)-phenyl)methanol (47), compound 55 was prepared from 1-bromobutane (24.2 mmol) and 4-hydroxy-benzyl alcohol (12.1 mmol) to give 55 as a white solid (83% isolated yield). 1-(Bromomethyl)-4-butoxybenzene (56). Following the procedure for the preparation of 1-(bromo-methyl)-4-(4-chlorobutoxy)benzene (48), compound 56 was prepared from (4- butoxyphenyl)methanol (55) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 56 as a light yellow oil. The residue was used in the next step without further purification. N-(4-Butoxybenzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-22). Following the procedure for the preparation of JHSW-m-01, JHSW-m-22 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2) (0.5 mmol) and 1-(bromomethyl)-4- butoxybenzene (56) (0.75 mmol) to give JHSW-m-22 as a light yellow oil (79% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.94 (s, 2H), 4.10-4.08 (m, 4H), 3.95-3.92 (m, 4H), 3.89-3.87 (m, 2H), 3.28 (s, 6H), 1.82-1.72 (m, 4H), 1.50-1.43 (m, 2H), 1.31 (s, 6H), 0.96 (t, J = 6.0 Hz, 3H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.01, 155.99, 142.97, 134.85, 127.25, 118.78, 115.01, 113.63, 70.01, 69.02, 67.89, 66.88, 65.38, 62.53, 56.95, 50.36, 37.98, 32.32, 31.77, 31.64, 31.16, 19.20, 13.82. HRMS m / z: [M-Br]+calcd. for C31H50NO3+: 484.3786, found 484.3792. Experimental procedure for the preparation of JHSW-m-23 (4-(4-Fluorobutoxy)phenyl)methanol (57). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl)methanol (47), compound 55 was prepared from 1- bromo-4-fluorobutane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 55 as a colorless oil (73% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.59- 4.44 (m, 4H), 4.00 (t, J = 4.0 Hz, 2H), 1.92-1.83 (m, 4H). HRMS m / z: [M+H]+calcd. for C11H16O2F+: 199.1134, found 199.1162. 1-(Bromomethyl)-4-(4-fluorobutoxy)benzene (58). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 58 was prepared from (4-(4-fluoro butoxy)phenyl)methanol (57) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 58 as a light yellow oil. The residue was used in the next step without further purification. N-(4-(4-Fluorobutoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-23). Following the procedure for the preparation of JHSW-m-01, JHSW-m-23 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethanamine (2) (0.5mmol) and 1-(bromomethyl)-4-(4- fluorobutoxy)benzene (58) (0.75 mmol) to give JHSW-m-23 as a light yellow oil (70% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.45 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.55 (s, 2H), 4.12-4.10 (m, 2H), 4.04-4.01 (m, 2H), 3.98-3.95 (m, 2H), 3.84-3.82 (m, 2H), 3.51 (t, J = 4.0 Hz, 2H), 3.00 (s, 6H), 1.86-1.83 (m, 2H), 1.70 (s, 2H), 1.30 (s, 6H), 1.26-1.25 (m, 2H), 0.88-0.82 (m, 2H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 161.70, 156.40, 142.43, 134.75, 127.28, 119.49, 114.81, 113.62, 83.90 (d,1J = 162.6 Hz), 69.52, 68.31, 67.59, 66.94, 64.49, 56.40, 49.99, 37.64, 31.85, 31.32, 31.07, 31.04, 26.80 (d,2J = 19.0Hz), 24.85 (d,3J = 6.0 Hz). HRMS m / z: [M-Br]+calcd. for C31H49NO3F+: 502.3691, found 502.3723. Experimental procedure for the preparation of JHSW-m-24 4-(4-(Hydroxymethyl)phenoxy)butanenitrile (59). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 59 was prepared from 4- bromobutanenitrile (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 59 as a colorless oil (69% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.59 (d, J = 4.0 Hz, 2H), 4.07 (t, J = 4.0 Hz, 2H), 2.58 (t, J = 4.0 Hz, 2H), 2.14-2.10 (m, 2H). HRMS m / z: [M+H]+calcd. for C11H14NO2+: 192.1025, found 192.1043. 4-(4-(Bromomethyl)phenoxy)butanenitrile (60). Following the procedure for the preparation of 1-(bromo methyl)-4-(4-chlorobutoxy)benzene (48), compound 60 was prepared from 4-(4-(hydroxymethyl) phenoxy)butanenitrile (59) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 60 as a light yellow oil. The residue was used in the next step without further purification. N-(4-(3-Cyanopropoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-24). Following the procedure for the preparation of JHSW-m-01, JHSW-m-24 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2, 0.5 mmol) and 4-(4- (bromomethyl)phenoxy)butanenitrile (60, 0.75 mmol) to give JHSW-m-24 as a light yellow oil (76% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.47 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.0 Hz, 2H), 4.55 (s, 2H), 4.12-4.06 (m, 4H), 3.99-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.50 (t, J = 4.0 Hz, 2H), 3.00 (s, 6H), 2.57 (t, J = 4.0 Hz, 2H), 2.10- 2.04 (m, 2H), 1.70 (s, 2H), 1.30 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.35, 156.39, 142.44, 134.80, 127.29, 119.86, 119.74, 114.87, 113.62, 69.52, 68.28, 66.94, 66.07, 64.48, 62.70, 56.40, 50.02, 37.64, 31.85, 31.07, 31.04, 24.90, 13.56. HRMS m / z: [M-Br]+calcd. for C32H47N2O3+: 495.3583, found 495.3621. Experimental procedure for the preparation of JHSW-m-25 (4-((4-Bromobenzyl)oxy)phenyl)methanol (61). Following the procedure for the preparation of (4-(4-chloro butoxy)phenyl)methanol (47), compound 61 was prepared from 1- bromo-4-(bromomethyl) benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 61 as a colorless oil (79% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.0 Hz, 2H), 7.31-7.28 (m, 4H), 6.92 (d, J = 8.0 Hz, 2H), 5.02 (s, 2H), 4.60 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H14BrO2+: 293.0177, found 293.0161. 1-Bromo-4-((4-(bromomethyl)phenoxy)methyl)benzene (62). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 62 was prepared from (4-((4-bromo benzyl)oxy)phenyl)methanol (61) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 62 as a light yellow oil. The residue was used in the next step without further purification. N-(4-((4-Bromobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-25). Following the procedure for the preparation of JHSW-m-01, JHSW-m-25 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl) phenoxy)ethoxy) ethanamine (2) (0.5 mmol) and 1-bromo-4-((4- (bromomethyl)phenoxy)methyl)benzene (62) (0.75 mmol) to give JHSW-m-25 as a white solid (80% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.99 (s, 2H), 4.98 (s, 2H), 4.10-4.08 (m, 4H), 3.95-3.93 (m, 2H), 3.89-3.87 (m, 2H), 3.29 (s, 6H), 1.78 (s, 2H), 1.31 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.27, 155.97, 143.00, 135.27, 135.00, 131.86, 129.15, 127.27, 122.20, 119.62, 115.38, 113.61, 70.02, 69.36, 68.75, 66.86, 65.33, 62.53, 56.94, 50.39, 37.99, 32.33, 31.79, 31.65. HRMS m / z: [M-Br]+calcd. for C34H47N2O3Br+: 596.2734, found 596.2766. Experimental procedure for the preparation of JHSW-m-26 (4-((3-Bromobenzyl)oxy)phenyl)methanol (63). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 63 was prepared from 1- bromo-3-(bromomethyl)benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 63 as a colorless oil (71% isolated yield). 1-Bromo-3-((4-(bromomethyl)phenoxy)methyl)benzene (64). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 64 was prepared from (4-((3-bromo benzyl)oxy)phenyl)methanol (63) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 64 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3-Bromobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-26). Following the procedure for the preparation of JHSW-m-01, JHSW-m-25 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2) (0.5 mmol) and 1-bromo-3-((4- (bromomethyl)phenoxy)methyl)benzene (64) (0.75 mmol) to give JHSW-m-25 as a white solid (73% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.63 (m, 1H), 7.51-7.47 (m, 3H), 7.43-7.41 (m, 1H), 7.31-7.27 (m, 3H), 7.04 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 5.10 (s, 2H), 4.54 (s, 2H), 4.12-4.10 (m, 2H), 3.98-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.51-3.48 (m, 2H), 3.00 (s, 6H), 1.70 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.16, 156.39, 142.45, 139.57, 134.83, 130.99, 130.55, 130.33, 127.29, 126.40, 122.04, 120.05, 115.22, 113.62, 69.54, 68.84, 68.26, 66.94, 64.47, 56.40, 54.34, 50.12, 37.64, 31.85, 31.08, 31.04. HRMS m / z: [M- Br]+calcd. for C34H47N2O3Br+: 596.2734, found 596.2766. Experimental procedure for the preparation of JHSW-m-27 (4-((4-(Bromomethyl)benzyl)oxy)phenyl)methanol (65). This compound was prepared using the literature method (Smet, M.; et al. Coll. Czech. Chem. Commun. 2004, 69, 1097- 1108). N-(4-((4-(Hydroxymethyl)phenoxy)methyl)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl) phenoxy)ethoxy)ethanaminium bromide (JHSW-m-27). Following the procedure for the preparation of JHSW-m-01, JHSW-m-27 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl) phenoxy)ethoxy) ethanamine (2) (0.5 mmol) and (4-((4- (bromomethyl)benzyl)oxy)phenyl)methanol (65) (0.75 mmol) to give JHSW-m-27 as a white solid (69% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.58-7.52 (m, 4H), 7.29-7.25 (m, 4H), 6.93 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.0 Hz, 2H), 5.11 (s, 2H), 4.60 (s, 2H), 4.47 (d, J = 4.0 Hz, 2H), 4.13- 4.10 (m, 2H), 3.99-3.97 (m, 2H), 3.85-3.83 (m, 2H), 3.53 (t, J = 4.0 Hz, 2H), 3.03 (s, 6H), 1.70 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 157.69, 156.39, 142.45, 140.28, 134.95, 133.46, 128.36, 127.94, 127.29, 127.11, 114.57, 113.62, 69.54, 68.97, 68.29, 66.93, 64.47, 63.22, 63.08, 56.40, 50.40, 37.64, 31.85, 31.07, 31.04. HRMS m / z: [M-Br]+calcd. for C35H50NO4+: 548.3733, found 548.3753. Experimental procedure for the preparation of JHSW-m-28 (3-((4-(Bromomethyl)benzyl)oxy)phenyl)methanol (66). Following the procedure for the preparation of (4-((4-(bromomethyl)benzyl)oxy)phenyl)methanol (65), compound 66 was prepared from 1,4-bis(bromo methyl)benzene and 3-(hydroxymethyl)phenol to give 66 as a white solid (77% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.41 (m, 4H), 7.28 (d, J = 8.0 Hz, 1H), 7.01-7.00 (m, 1H), 6.97-6.95 (m, 1H), 6.91-6.88 (m, 1H), 5.07 (s, 2H), 4.67 (s, 2H), 4.50 (s, 2H). HRMS m / z: [M+H]+calcd. for C15H16BrO2+: 307.0334, found 307.0362. N-(4-((3-(Hydroxymethyl)phenoxy)methyl)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl) phenoxy)ethoxy)ethanaminium bromide (JHSW-m-28). Following the procedure for the preparation of JHSW-m-01, JHSW-m-28 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl) phenoxy)ethoxy)ethanamine (2) (0.5 mmol) and (3-((4- (bromomethyl)benzyl)oxy)phenyl)methanol (66) (0.75 mmol) to give JHSW-m-28 as a white solid (68% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.55 (m, 4H), 7.27 (d, J = 8.0 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 7.00 (m, 1H), 6.91 (d, J = 8.0 Hz, 1H), 6.87-6.85 (m, 1H), 6.80 (d, J = 8.0 Hz, 2H), 5.13 (s, 2H), 4.57 (s, 2H), 4.52 (d, J = 4.0 Hz, 2H), 4.13-4.11 (m, 2H), 3.99-3.98 (m, 2H), 3.85- 3.83 (m, 2H), 3.53 (t, J = 4.0 Hz, 2H), 3.02 (s, 6H), 1.70 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 158.70, 156.38, 144.19, 140.32, 133.43, 129.49, 129.41, 128.00, 127.29, 127.04, 119.30, 113.62, 113.26, 112.93, 69.55, 68.87, 66.93, 64.46, 63.41, 56.39, 55.06, 54.34, 50.43, 37.64, 31.85, 31.07, 31.04. HRMS m / z: [M-Br]+calcd. for C35H50NO4+: 548.3733, found 548.3747. Experimental procedure for the preparation of JHSW-m-29 N,N-Dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propoxy)propan-1- amine (67). Following the procedure for the preparation of N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2), compound 44 gave 67 as a colorless liquid (63% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.03 (t, J = 4.0 Hz, 2H), 3.58 (t, J = 4.0 Hz, 2H), 3.46 (t, J = 4.0 Hz, 2H), 2.02 (t, J = 4.0 Hz, 2H), 2.20 (s, 6H), 2.05-1.99 (m, 2H), 1.77-1.71 (m, 2H), 1.69 (s, 2H), 1.33 (s, 6H), 0.71 (s, 9H).13C NMR (100 MHz, CDCl3) δ 156.67, 142.10, 127.02, 113.69, 69.27, 67.40, 64.77, 57.01, 56.72, 45.55, 37.94, 32.33, 31.80, 31.71, 29.83, 28.02. HRMS m / z: [M+H]+calcd. for C22H40NO2+: 350.3059, found 350.3071. N-(4-(4-Chlorobutoxy)benzyl)-N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)propoxy) propan-1-aminium bromide (JHSW-m-29). Following the procedure for the preparation of JHSW-m-01, JHSW-m-29 was prepared from N,N-dimethyl-3-(3-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)pro-poxy)propan-1-amine (67) (0.5mmol) and 1- (bromomethyl)-4-(4-chlorobutoxy)benzene (48) (0.75 mmol) to give JHSW-m-29 as a light yellow oil (68% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.45 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz,, 2H), 6.78 (d, J = 8.0 Hz, 2H), 4.47 (s, 2H), 4.02-3.97 (m, 4H), 3.64 (t, J = 4.0 Hz, 2H), 3.55 (t, J = 4.0 Hz, 2H), 3.49 (t, J = 4.0 Hz, 2H), 3.34-3.30 (m, 2H), 2.93 (s, 6H), 2.06-2.02 (m, 2H), 1.96-1.95 (m, 2H), 1.89-1.84 (m, 4H), 1.69 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.67, 156.68, 142.12, 134.54, 127.22, 119.48, 114.83, 113.61, 67.33, 67.06, 66.79, 66.65, 64.60, 61.38, 56.42, 49.37, 44.97, 37.63, 31.87, 31.10, 31.07, 29.34, 29.08, 26.29, 23.04. HRMS m / z: [M-Br]+calcd. for C33H53NO3Cl+: 546.3709, found 546.3727. Experimental procedure for the preparation of JHSW-m-30 N-(4-Butoxybenzyl)-N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)propoxy)propan-1-aminium bromide (JHSW-m-30). Following the procedure for the preparation of JHSW-m-01, JHSW-m-30 was prepared from N,N-dimethyl-3-(3-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)propoxy) propan-1-amine (67) (0.5 mmol) and 1- (bromomethyl)-4-butoxybenzene (55) (0.75 mmol) to give JHSW-m-30 as a light yellow oil (78% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.0 Hz, 2H), 4.85 (s, 2H), 3.98 (t, J = 4.0 Hz, 2H), 3.93 (t, J = 4.0 Hz, 2H), 3.59-3.52 (m, 6H), 3.23 (s, 6H), 2.15-2.10 (m, 2H), 2.03-1.96 (m, 2H), 1.79-1.73 (m, 2H), 1.68 (s, 2H), 1.52-1.43 (m, 2H), 1.31 (s, 6H), 0.97 (t, J = 4.0 Hz, 3H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.06, 156.48, 142.47, 134.62, 127.14, 118.57, 115.02, 113.60, 67.89, 67.70, 67.05, 66.85, 64.44, 61.31, 56.96, 49.83, 37.96, 32.33, 31.78, 31.68, 31.17, 29.55, 23.71, 19.22, 13.84. HRMS m / z: [M-Br]+calcd. for C33H54NO3+: 512.4099, found 512.4135. Experimental procedure for the preparation of JHSW-m-31 N-(4-((4-Bromobenzyl)oxy)benzyl)-N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)prop-oxy)propan-1-aminium bromide (JHSW-m-31). Following the procedure for the preparation of JHSW-m-01, JHSW-m-31 was prepared from N,N-dimethyl-3-(3-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)prop-oxy)propan-1-amine (67) (0.5mmol) and 1-bromo- 4-((4-(bromomethyl)phenoxy)methyl)benzene (62) (0.75 mmol) to give JHSW-m-31 as a light yellow oil (72% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0Hz, 2H), 6.77 (d, J = 8.0Hz, 2H), 4.97 (s, 2H), 4.88 (s, 2H), 3.98 (t, J = 4.0 Hz, 2H), 3.59-3.52 (m, 6H), 3.23 (s, 6H), 2.15-2.12 (m, 2H), 2.02-1.96 (m, 2H), 1.67 (s, 2H), 1.30 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.32, 156.46, 142.53, 135.25, 134.79, 131.86, 129.18, 127.16, 122.21, 119.41, 115.40, 113.61, 69.36, 67.73, 66.82, 64.46, 63.64, 61.35, 56.96, 49.88, 37.96, 32.33, 31.78, 31.66, 29.55, 23.71. HRMS m / z: [M-Br]+calcd. for C36H51NO3Br+: 624.3047, found 624.3059. Experimental procedure for the preparation of JHSW-m-32 N,N-Dimethyl-2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethan-1-amine (68). A mixture of 2-dimethyl-aminoethyl chloride (30 mmol), 10M NaOH (20.6 mL), tetrabutylammonium bromide (TBAB, 2.4 mmol) and 4-(2,4,4-trimethylpentan-2-yl)phenol (12 mmol) in toluene (20.6 mL) was vigorous stirred at 80 °C for 18 h. The reaction mixture was cooled to 23 °C. The layers were separated, and the aqueous layers were extracted with toluene (2×20 mL). The combined organic layers were washed successively with H2O and saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes / ethyl acetate, 9 / 1, acetonitrile / CHCl3 / Et3N, 1 / 1 / 0.01) to give 68 as a light yellow liquid (70% isolated yield). HRMS m / z: [M+H]+calcd. For C18H32NO+: 278.2439, found 278.2457. 1-(Bromomethyl)-4-phenethoxybenzene (69). Following the procedure for the preparation of 1-(bromo-methyl) -4-(4-chlorobutoxy)benzene (48), compound 69 was prepared from (4-((5-chloropentyl)oxy)-phenyl) methanol (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 69 as a light yellow oil. The material was used in the next step without further purification. N,N-Dimethyl-N-(4-phenethoxybenzyl)-2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethanaminium bromide (JHSW-m-32). Following the procedure for the preparation of JHSW-m-01, JHSW-m-32 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68) (0.5 mmol) and 1-(bromomethyl)-4- phenethoxybenzene (69) ( 0.75 mmol) to give JHSW-m-32 as a light yellow oil (80% isolated yield).1H NMR (400 MHz, CD3CN) δ 7.50 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.31- 7.28 (m, 4H), 7.24-7.20 (m, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H), 4.43-4.41 (m, 2H), 4.23 (t, J = 4.0 Hz, 2H), 4.75-4.73 (m, 2H), 3.08-3.05 (m, 8H), 1.71 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.59, 155.28, 143.43, 138.60, 134.76, 129.07, 128.43, 127.39, 126.45, 119.50, 114.91, 113.82, 68.71, 68.28, 62.61, 61.72, 56.34, 50.09, 37.74, 35.11, 31.86, 31.07, 31.05. HRMS m / z: [M-Br]+calcd. for C33H46NO2+: 488.3524, found 488.3546. Experimental procedure for the preparation of JHSW-m-33 (4-(2-(Benzyloxy)ethoxy)phenyl)methanol (71). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 71 was prepared from ((2-bromoethoxy)methyl)benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 71 as a white solid (63% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.38-7.30 (m, 5H), 7.28-7.27 (m, 2H), 6.90 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H), 4.59 (d, J = 4.0 Hz, 2H), 4.16-4.13 (m, 2H), 3.84-3.82 (m, 2H). HRMS m / z: [M+H]+calcd. for C16H19O3+: 259.1334, found 259.1352. 1-(2-(Benzyloxy)ethoxy)-4-(bromomethyl)benzene (72). Following the procedure for the preparation of 1-(bromomethyl) -4-(4-chlorobutoxy)benzene (48), compound 72 was prepared from (4-(2-(benzyloxy) ethoxy)phenyl)methanol (71) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 72 as a light yellow oil. The residue was used in thee next step without further purification. N-(4-(2-(Benzyloxy)ethoxy)benzyl)-N,N-dimethyl-2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethan-aminium bromide (JHSW-m-33). Following the procedure for the preparation of JHSW-m-01, JHSW-m-33 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68) (0.5 mmol) and 1-(2-(benzyloxy)ethoxy)-4- (bromomethyl)benzene (72) (0.75 mmol) to give JHSW-m-33 as a light yellow oil (77% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.51 (d, J = 8.0 Hz, 2H), 7.35-7.32 (m, 6H), 7.30-7.25 (m, 1H), 7.02 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H), 4.56 (s, 2H), 4.43 (m, 2H), 4.19-4.16 (m, 2H), 3.81-3.79 (m, 2H), 3.75-3.72 (m, 2H), 3.07 (s, 6H), 1.72 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.58, 155.28, 143.43, 138.60, 134.76, 128.35, 127.68, 127.57, 127.40, 119.56, 114.96, 113.82, 72.67, 68.39, 68.29, 67.71, 62.64, 61.71, 56.34, 50.05, 37.74, 31.86, 31.06, 31.06. HRMS m / z: [M-Br]+calcd. for C34H48NO3+: 528.3629, found 528.3677. Experimental procedure for the preparation of JHSW-m-34 2-(4-(Hydroxymethyl)phenoxy)-1-(4-(pyrrolidin-1-yl)phenyl)ethan-1-one (73). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 73 was prepared from 2-bromo-1-(4-(pyrrolidin-1-yl)phenyl)ethan-1-one (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 73 as a white solid (73% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.0 Hz, 2H), 5.17 (s, 2H), 4.59 (s, 2H), 3.39-3.35 (m, 4H), 2.07-2.01 (m, 4H). HRMS m / z: [M+H]+calcd. for C19H22NO3+: 312.1600, found 312.1624. 2-(4-(Bromomethyl)phenoxy)-1-(4-(pyrrolidin-1-yl)phenyl)ethan-1-one (74). Following the procedure for the preparation of 1-(bromomethyl) -4-(4-chlorobutoxy)benzene (48), compound 74 was prepared from 2-(4-(hydroxymethyl)phenoxy)-1-(4-(pyrrolidin-1- yl)phenyl)ethan-1-one (73) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 74 as a light yellow oil. The material was used in the next step without further purification. N,N-Dimethyl-N-(4-(2-oxo-2-(4-(pyrrolidin-1-yl)phenyl)ethoxy)benzyl)-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethan-1-aminium bromide (JHSW-m-34). Following the procedure for the preparation of JHSW-m-01, JHSW-m-34 was prepared from N,N-dimethyl- 2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy) ethanamine (68) (0.5 mmol) and 2-(4- (bromomethyl)phenoxy)-1-(4-(pyrrolidin-1-yl)phenyl)ethan-1-one (74) (0.75 mmol) to give JHSW-m-34 as a light yellow oil (70% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.83 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.57 (d, J = 8.0 Hz, 2H), 5.36 (s, 2H), 4.57 (s, 2H), 4.41 (m, 2H), 3.71-3.68 (m, 2H), 3.36-3.33 (m, 4H), 3.05 (s, 6H), 2.02-1.98 (m, 4H), 1.72 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 191.00, 160.40, 155.26, 151.73, 143.47, 134.64, 130.05, 127.40, 121.49, 119.62, 115.10, 113.80, 110.89, 75.56, 69.78, 61.67, 56.33, 53.29, 50.17, 47.42, 37.74, 31.86, 31.34, 31.05, 25.06. HRMS m / z: [M-Br]+calcd. for C37H51N2O3+: 571.3895, found 571.3947. Experimental procedure for the preparation of JHSW-m-35 2-(4-(Hydroxymethyl)phenoxy)-1-phenylethan-1-one (75). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 75 was prepared from 2-bromo-1-phenylethan-1-one (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 75 as a white solid (82% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.0 Hz, 2H), 7.64-7.60 (m, 1H), 7.50 (t, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 5.28 (s, 2H), 4.61 (s, 2H). HRMS m / z: [M+H]+calcd. for C15H15O2+: 243.1021, found 243.1053. 2-(4-(Bromomethyl)phenoxy)-1-phenylethan-1-one (76). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 76 was prepared from 2-(4-(hydroxy-methyl)phenoxy)-1-phenylethan-1-one (75) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 76 as a light yellow oil. The material was used in the next step without further purification. N,N-Dimethyl-N-(4-(2-oxo-2-phenylethoxy)benzyl)-2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethan-1-aminium bromide (JHSW-m-35). Following the procedure for the preparation of JHSW-m-01, JHSW-m-35 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethan-1-amine (68) (0.5 mmol) and 2-(4- (bromomethyl)phenoxy)-1-phenylethan-1-one (76) (0.75 mmol) to give JHSW-m-35 as a light yellow oil (75% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.0 Hz, 2H), 7.65-7.60 (m, 3H), 7.51 (t, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 5.36 (s, 2H), 5.09 (s, 2H), 4.46-4.44 (m, 2H), 4.18-4.15 (m, 2H), 3.36 (s, 6H), 1.80 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 193.77, 159.93, 154.62, 144.21, 135.01, 134.25, 134.21, 129.03, 128.08, 127.52, 119.92, 115.50, 113.63, 70.52, 68.83, 62.24, 62.02, 56.90, 50.41, 38.09, 32.33, 31.80, 31.63. HRMS m / z: [M-Br]+calcd. for C33H44NO3+: 502.3316, found 502.3342. Experimental procedure for the preparation of JHSW-m-36 (4-(Cyclohexylmethoxy)phenyl)methanol (77). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl)methanol (47), compound 77 was prepared from (bromomethyl)cyclohexane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 77 as a white solid (62% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.61 (s, 2H), 3.74 (d, J = 4.0 Hz, 2H), 1.90-1.84 (m, 2H), 1.78-1.68 (m, 3H), 1.32-1.24 (m, 2H), 1.09-1.00 (m, 2H). HRMS m / z: [M+H]+calcd. for C14H21O2+: 221.1542, found 221.1554. 1-(Bromomethyl)-4-(cyclohexylmethoxy)benzene (78). Following the procedure for the preparation of 1-(bromomethyl) -4-(4-chlorobutoxy)benzene (48), compound 78 was prepared from (4-(cyclohexyl methoxy)phenyl)methanol (77) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 78 as a light yellow oil. The material was used in the next step without further purification. N-(4-(Cyclohexylmethoxy)benzyl)-N,N-dimethyl-2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethan-aminium bromide (JHSW-m-36). Following the procedure for the preparation of JHSW-m-01, JHSW-m-36 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68, 0.5 mmol) and 1-(bromomethyl)-4- (cyclohexylmethoxy)benzene (78, 0.75 mmol) to give JHSW-m-36 as a light yellow oil (81% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 5.08 (s, 2H), 4.46-4.44 (m, 2H), 4.19-4.17 (m, 2H), 3.72 (d, J = 4.0 Hz, 2H), 3.38 (s, 6H), 1.92 (m, 1H), 1.86-1.82 (m, 2H), 1.77-1.71 (m, 4H), 1.68 (s, 2H), 1.31 (s, 6H), 1.28-1.19 (m, 2H), 1.08-1.00 (m, 2H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.26, 154.65, 144.14, 134.87, 127.49, 118.61, 115.09, 113.63, 73.64, 69.17, 62.30, 61.84, 56.90, 50.34, 38.08, 37.62, 32.33, 31.79, 31.63, 29.84, 26.45, 25.77. HRMS m / z: [M-Br]+calcd. for C32H50NO2+: 480.3837, found 480.3863. Experimental procedure for the preparation of JHSW-m-37 (4-(2-(1,3-Dioxan-2-yl)ethoxy)phenyl)methanol (79). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 79 was prepared from 2- (2-bromoethyl)-1,3-dioxane (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 79 as a white solid (55% isolated yield). δ 7.24 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.77 (m, 1H), 4.57 (d, J = 4.0 Hz, 2H), 4.11-4.03 (m, 4H), 3.80-3.73 (m, 2H), 2.15-2.01 (m, 4H). HRMS m / z: [M+H]+calcd. for C13H19O4+: 239.1283, found 239.1297. 2-(2-(4-(bromomethyl)phenoxy)ethyl)-1,3-dioxane (80). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 80 was prepared from (4-(2-(1,3-dioxan-2-yl)ethoxy)phenyl)methanol (80, 4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 80 as a light yellow oil. The material was used in the next step without further purification. N-(4-(2-(1,3-Dioxan-2-yl)ethoxy)benzyl)-N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy) ethanaminium bromide (JHSW-m-37). Following the procedure for the preparation of JHSW-m-01, JHSW-m-37 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68, 0.5 mmol) and 2-(2-(4- (bromomethyl)phenoxy)ethyl)-1,3-dioxane (80, 0.75 mmol) to give JHSW-m-37 as a light yellow oil (85% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.49 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 4.74 (m, 1H), 4.61-4.59 (m, 2H), 4.43-4.42 (m, 2H), 4.07 (t, J = 4.0 Hz, 2H), 4.03-4.00 (m, 2H), 3.77-3.70 (m, 4H), 3.06 (s, 6H), 2.00-1.95 (m, 4H), 1.72 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.69, 155.27, 153.12, 143.46, 134.75, 127.40, 114.92, 113.81, 99.11, 71.27, 68.44, 66.51, 63.68, 62.67, 61.68, 56.33, 50.09, 37.74, 34.76, 31.86, 31.05, 25.59. HRMS m / z: [M-Br]+calcd. for C31H48NO4+: 498.3578, found 498.3566. Experimental procedure for the preparation of JHSW-m-36-2 4-(Hydroxymethyl)phenyl 4-bromobutanoate (81). Anhydrous Et3N (1.1 mL, 9 mmol) was added to a solution of 4-hydroxybenzyl alcohol (8 mmol) in anhydrous THF (25 mL) under Ar.4-Bromobutanoyl chloride (0.7 mL, 9 mmol) was added dropwise to the solution over 30 min at 0 ℃. The mixture was stirred for 3 h at 23 °C. The reaction mixture was filtered through Celite and concentrated in vacuo. The residue was dissolved in ethyl acetate and the organic solution was washed with brine and saturated NaHCO3solution. It was then dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate / dichloromethane=1 / 2) to obtain 81 as a light yellow liquid (70% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.35 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H), 3.53 (t, J = 4.0 Hz, 2H), 2.76 (t, J = 4.0 Hz, 2H), 2.31-2.25 (m, 2H). HRMS m / z: [M+H]+calcd. for C11H14O3Br+: 273.0126, found 273.0142. 4-(Bromomethyl)phenyl 4-bromobutanoate (82). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 82 was prepared from 4-(hydroxymethyl) phenyl 4-bromobutanoate (81, 4mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give 82 as a light yellow oil. The material was used in the next step without further purification. N-(4-((4-Bromobutanoyl)oxy)benzyl)-N,N-dimethyl-2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethan-aminium bromide (JHSW-m-36-2). Following the procedure for the preparation of JHSW-m-01, JHSW-m-36-2 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68) (0.5 mmol) and 4-(bromomethyl)phenyl 4- bromobutanoate (82) (0.75 mmol) to give JHSW-m-36-2 as a light yellow oil (77% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.67 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 2H), 4.78 (s, 2H), 4.64-4.43 (m, 2H), 3.82-3.80 (m, 2H), 3.57 (t, J = 4.0 Hz, 2H), 3.14 (s, 6H), 2.75 (t, J = 4.0 Hz, 2H), 2.26-2.21 (m, 2H), 1.72 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CD3CN) δ 171.04, 155.29, 152.60, 143.44, 134.69, 127.39, 125.29, 122.53, 113.84, 67.61, 62.95, 61.75, 61.15, 56.34, 50.35, 37.75, 33.01, 32.30, 31.87, 31.07, 27.59. HRMS m / z: [M-Br]+calcd. for C29H43NO3Br+: 534.2401, found 534.2423. Experimental procedure for the preparation of JHSW-m-37-2 N-(4-(2-(Benzyloxy)ethoxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-37-2). Following the procedure for the preparation of JHSW-m-01, JHSW-m-37-2 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2) (0.5 mmol) and 1-(2- (benzyloxy)ethoxy)-4-(bromomethyl)benzene (72, 0.75 mmol) to give JHSW-m-37-2 as a light yellow oil (85% isolated yield). 1H NMR (400 MHz, CD3CN) δ 7.46 (d, J = 8.0 Hz, 2H), 7.34-7.26 (m, 7H), 6.97 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 4.56 (m, 4H), 4.17-4.15 (m, 2H), 4.12-4.10 (m, 2H), 3.98-3.96 (m, 2H), 3.84-3.82 (m, 2H), 3.80-3.78 (m, 2H), 3.52-3.49 (m, 2H), 3.00 (s, 6H), 1.69 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 160.59, 156.39, 142.43, 138.59, 134.76, 128.35, 127.68, 127.57, 127.29, 119.68, 114.88, 113.62, 72.66, 69.52, 68.38, 67.68, 66.94, 64.48, 62.72, 56.40, 54.35, 50.03, 37.64, 31.85, 31.08, 31.05. HRMS m / z: [M- Br]+calcd. for C36H52NO4+: 562.3891, found 562.3921. Experimental procedure for the preparation of JHSW-m-38 N,N-Dimethyl-N-(4-(2-oxo-2-phenylethoxy)benzyl)-2-(2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)eth-oxy)ethanaminium bromide (JHSW-m-38). Following the procedure for the preparation of JHSW-m-01, JHSW-m-38 was prepared from N,N-dimethyl-2-(2-(4- (2,4,4-trimethyl-pentan-2-yl)phenoxy)ethoxy)-ethanamine (2) (0.5 mmol) and 2-(4- (bromomethyl)phenoxy)-1-phenyl-ethan-1-one (76) (0.75 mmol) to give JHSW-m-38 as a light yellow oil (78% isolated yield). 1H NMR (400 MHz, CD3CN) δ 8.01-7.89 (m, 2H), 7.69-65 (m, 1H), 7.57-7.54 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 5.49 (s, 2H), 4.53 (s, 2H), 4.12-4.10 (m, 2H), 3.98-3.95 (m, 2H), 3.84-3.82 (m, 2H), 3.50- 3.48 (m, 2H), 3.00 (s, 6H), 1.69 (s, 2H), 1.29 (s, 6H), 0.67 (s, 9H).13C NMR (100 MHz, CD3CN) δ 194.04, 159.95, 156.38, 142.44, 134.74, 133.97, 128.93, 127.85, 127.29, 126.52, 120.14, 115.04, 113.61, 70.35, 69.51, 68.23, 66.91, 64.46, 56.39, 54.35, 50.10, 37.63, 31.85, 31.07, 31.03. HRMS m / z: [M-Br]+calcd. for C35H48NO4+: 546.3578, found 546.3595. Experimental procedure for the preparation of JHSW-m-39 N,N-Dimethyl-N-(4-(2-oxo-2-(4-(pyrrolidin-1-yl)phenyl)ethoxy)benzyl)-2-(2-(4- (2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanaminium bromide (JHSW-m-39). Following the procedure for the preparation of JHSW-m-01, JHSW-m-39 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)ethanamine (2) (0.5 mmol) 2-(4-(bromomethyl)phenoxy)-1-(4-(pyrrolidin-1-yl) phenyl)ethan-1-one (74) (0.75 mmol) to give JHSW-m-39 as a light yellow oil (72% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.0 Hz, 2H), 5.23 (s, 2H), 4.88 (s, 2H), 4.12-4.08 (m, 4H), 3.97 (m, 2H), 3.89-3.87 (m, 2H), 3.40-3.37 (m, 4H), 3.25 (s, 6H), 2.07-2.04 (m, 4H), 1.68 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 191.21, 160.20, 155.98, 151.62, 142.91, 134.87, 130.49, 127.25, 121.61, 119.62, 115.39, 113.62, 111.03, 70.12, 69.96, 68.73, 66.84, 65.30, 62.52, 56.95, 50.31, 47.63, 37.98, 32.33, 31.79, 31.66, 25.43. HRMS m / z: [M-Br]+calcd. for C39H55N2O4+: 615.4157, found 615.4179. Experimental procedure for the preparation of JHSW-m-40 N,N'-(1,3-Phenylenebis(methylene))bis(N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethan-aminium) dibromide (JHSW-m-40). To liquid 1,3- bis(bromomethyl)benzene (0.36 mmol) was added N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethan-1-amine (68, 0.8 mmol) in dichloro-methane (8 mL). After being stirred at 23 °C for 8 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, acetonitrile / dichloromethane=1 / 1, then methanol / dichloromethane=1 / 4) to give JHSW-m-40 as a white solid (68% isolated yield). 1H NMR (400 MHz, CDCl3) δ 8.59 (m, 1H), 7.91 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 4H), 6.82 (d, J = 8.0 Hz, 4H), 5.22 (s, 4H), 4.50 (m, 4H), 4.14 (m, 4H), 3.45 (s, 12H), 1.68 (s, 4H), 1.31 (s, 12H), 0.69 (s, 18H).13C NMR (100 MHz, CDCl3) δ 154.60, 144.23, 138.80, 135.72, 135.17, 128.62, 127.53, 113.76, 68.23, 62.82, 62.25, 56.89, 51.25, 38.09, 32.35, 31.82, 31.66. HRMS m / z: [M-2Br]2+calcd. for C44H70N2O22+: 329.2713, found 329.2731. Experimental procedure for the preparation of JHSW-m-41 N,N'-(1,4-Phenylenebis(methylene))bis(N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethan-aminium) dibromide (JHSW-m-41). Following the procedure for the preparation of JHSW-m-40, JHSW-m-41 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethan-1-amine (68) (0.8 mmol) and 1,4- bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-41 as a white solid (78% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.71 (m, 4H), 7.29 (d, J = 8.0 Hz, 4H), 6.89 (d, J = 8.0 Hz, 4H), 4.73 (s, 4H), 4.50-4.48 (m, 4H), 3.80-3.77 (m, 4H), 3.09 (s, 12H), 1.67 (s, 4H), 1.27 (s, 12H), 0.65 (s, 18H).13C NMR (100 MHz, DMSO-d6) δ 155.55,142.97, 134.01, 130.51, 127.50, 114.35, 63.34, 61.79, 56.66, 55.40, 50.35, 38.14, 32.49, 32.08, 32.03. HRMS m / z: [M- 2Br]2+calcd. for C44H70N2O22+: 329.2713, found 329.2731. Experimental procedure for the preparation of JHSW-m-42 N,N'-(1,2-Phenylenebis(methylene))bis(N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethan-aminium) dibromide (JHSW-m-42). Following the procedure for the preparation of JHSW-m-40, JHSW-m-42 was prepared from N,N-dimethyl-2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethanamine (68) (0.8 mmol) and 1,2-bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-42 as a white solid (64% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.84-7.81 (m, 2H), 7.71-7.69 (m, 2H), 7.27 (d, J = 8.0 Hz, 4H), 6.87 (d, J = 8.0 Hz, 4H), 4.95 (s, 4H), 4.47-4.45 (m, 4H), 3.93-3.91 (m, 4H), 3.08 (s, 12H), 1.66 (s, 4H), 1.26 (s, 12H), 0.64 (s, 18H).13C NMR (100 MHz, DMSO-d6) δ 155.54, 142.92, 136.15, 131.35, 129.88, 127.48, 114.33, 64.66, 63.22, 61.77, 56.67, 49.77, 38.13, 32.49, 32.07, 32.02. HRMS m / z: [M-2Br]2+calcd. for C44H70N2O22+: 329.2713, found 329.2731. Experimental procedure for the preparation of JHSW-m-43 N,N'-(1,2-Phenylenebis(methylene))bis(N,N-dimethyl-2-(4-(2,4,4-trimethylpentan- 2-yl)phenoxy)ethan-aminium) dibromide (JHSW-m-43). Following the procedure for the preparation of JHSW-m-40, JHSW-m-43 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2, 0.8 mmol) and 1,3- bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-43 as a white solid (69% isolated yield). 1H NMR (400 MHz, CDCl3) δ 8.50 (bs, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 4H), 6.73 (d, J = 8.0 Hz, 4H), 5.08 (s, 4H), 4.10-4.07 (m, 8H), 3.89-3.86 (m, 8H), 3.34 (s, 12H), 1.66 (s, 4H), 1.29 (s, 12H), 0.67 (s, 18H).13C NMR (100 MHz, CDCl3) δ 155.96, 142.95, 138.70, 135.65, 130.03, 128.63, 127.26, 113.66, 70.00, 67.90, 66.95, 65.18, 63.17, 56.91, 51.14, 37.98, 32.33, 31.81, 31.68. HRMS m / z: [M-2Br]2+calcd. for C48H78N2O42+: 373.2976, found 373.2968. Experimental procedure for the preparation of JHSW-m-44 N,N'-(1,4-Phenylenebis(methylene))bis(N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium) dibromide (JHSW-m-44). Following the procedure for the preparation of JHSW-m-40, JHSW-m-44 was prepared from N,N- dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy) ethoxy)ethanamine (2) (0.8 mmol) and 1,4-bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-44 as a white solid (73% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.66 (s, 4H), 7.20 (d, J = 8.0 Hz, 4H), 6.78 (d, J = 8.0 Hz, 4H), 5.66 (s, 4H), 4.09-4.07 (m, 4H), 3.99-3.97 (m, 4H), 3.81-3.79 (m, 4H), 3.57-3.55 (m, 4H), 3.02 (s, 12H), 1.62 (s, 4H), 1.23 (s, 12H), 0.61 (s, 18H).13C NMR (100 MHz, DMSO- d6) δ 156.43, 142.04, 133.94, 130.50, 127.41, 114.05, 69.34, 67.07, 64.41, 63.22, 61.69, 56.76, 50.32, 38.02, 32.46, 32.01, 31.99. HRMS m / z: [M-2Br]2+calcd. for C48H78N2O42+: 373.2976, found 373.2968. Experimental procedure for the preparation of JHSW-m-45 N,N'-(1,2-Phenylenebis(methylene))bis(N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium) dibromide (JHSW-m-45). Following the procedure for the preparation of JHSW-m-40, JHSW-m-45 was prepared from N,N- dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)-ethoxy)ethan-1-amine (2, 0.8 mmol) and 1,2-bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-45 as a white solid (61% isolated yield). 1H NMR (400 MHz, DMSO-d6) δ 7.76-7.74 (m, 2H), 7.66-7.64 (m, 2H), 7.21 (d, J = 8.0 Hz, 4H), 6.77 (d, J = 8.0 Hz, 4H), 4.83 (s, 4H), 4.06-4.04 (m, 4H), 3.95-3.93 (m, 4H), 3.79- 3.76 (m, 4H), 3.68-3.66 (m, 4H), 2.99 (s, 12H), 1.63 (s, 4H), 1.24 (s, 12H), 0.62 (s, 18H).13C NMR (100 MHz, DMSO-d6) δ 156.41, 142.05, 136.09, 131.24, 129.84, 127.42, 114.01, 69.30, 67.01, 64.78, 64.33, 63.29, 56.75, 49.69, 38.03, 32.48, 32.02, 32.00. HRMS m / z: [M-2Br]2+calcd. for C48H78N2O42+: 373.2976, found 373.2968. Experimental procedure for the preparation of JHSW-m-46 N,N'-(1,3-Phenylenebis(methylene))bis(N,N-dimethyl-3-(3-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) propoxy)propan-1-aminium) dibromide (JHSW-m-46). Following the procedure for the preparation of JHSW-m-40, JHSW-m-46 was prepared from N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phen-oxy)propoxy)propan-1-amine (67) (0.8 mmol) and 1,3-bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-46 as a white solid (61% isolated yield).1H NMR (400 MHz, CDCl3) δ 8.67 (bs, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.45 (t, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 4H), 6.78 (d, J = 8.0 Hz, 4H), 4.97 (s, 4H), 3.98 (t, J = 4.0 Hz, 4H), 3.63-3.56 (m, 12H), 3.22 (s, 12H), 2.18-2.13 (m, 4H), 2.02-1.96 (m, 4H), 1.68 (s, 4H), 1.31 (s, 12H), 0.69 (s, 18H).13C NMR (100 MHz, CDCl3) δ 156.45, 142.47, 138.75, 135.39, 131.22, 128.46, 127.17, 113.66, 67.75, 66.76, 64.46, 63.20, 60.93, 56.95, 50.29, 37.97, 32.34, 31.80, 31.72, 29.51, 23.71. HRMS m / z: [M-2Br]2+calcd. for C52H86N2O42+: 401.3289, found 401.3301. Experimental procedure for the preparation of JHSW-m-47 N,N'-(1,4-Phenylenebis(methylene))bis(N,N-dimethyl-3-(3-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) propoxy)propan-1-aminium) dibromide (JHSW-m-47). Following the procedure for the preparation of JHSW-m-40, JHSW-m-47 was prepared from N,N-dimethyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phen-oxy)propoxy)propan-1-amine (67) (0.8 mmol) and 1,4-bis(bromomethyl)benzene (0.36 mmol) to give JHSW-m-47 as a white solid (69% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 4H), 7.22 (d, J = 8.0 Hz, 4H), 6.75 (d, J = 8.0 Hz, 4H), 5.22 (s, 4H), 3.96 (t, J = 4.0 Hz, 4H), 3.58-3.55 (m, 12H), 3.17 (s, 12H), 2.22-2.19 (m, 4H), 2.01-1.95 (m, 4H), 1.67 (s, 4H), 1.31 (s, 12H), 0.68 (s, 18H).13C NMR (100 MHz, CDCl3) δ 156.42, 142.39, 134.13, 129.97, 127.14, 113.63, 67.74, 66.91, 65.66, 64.51, 63.00, 56.93, 49.96, 37.95, 32.33, 31.79, 31.71, 29.51, 23.75. HRMS m / z: [M-2Br]2+calcd. for C52H86N2O42+: 401.3289, found 401.3303. Experimental procedure for the preparation of JHSW-m-48 (4-((2-Bromobenzyl)oxy)phenyl)methanol (83). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl)methanol (47), compound 83 was prepared from 1- bromo-2-(bromomethyl)benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 83 as a white solid (88% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.60-7.53 (m, 2H), 7.35-7.29 (m, 3H), 7.21-7.17 (td, J = 8.0, 2.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 4.62 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H14O2Br+: 293.0177, found 293.0193. 1-Bromo-2-((4-(bromomethyl)phenoxy)methyl)benzene (84). Following the procedure for the prepar-ation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 84 was prepared from ((4-((2-bromobenzyl)oxy)phenyl)methanol (83) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloromethane (4 mL) to give light yellow oil. The material was used in the next step without further purification. N-(4-((2-Bromobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy) ethanaminium bromide (JHSW-m-48). Following the procedure for the preparation of JHSW-m-01, JHSW-m-48 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy--ethanamine (2) (0.5 mmol) and 1-bromo-2-((4- (bromomethyl)phenoxy)methyl)benzene (84, 0.75 mmol) to give JHSW-m-48 as a light yellow oil (79% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.59-7.57 (m, 3H), 7.50-7.48 (m, 1H), 7.34-7.30 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.21-7.17 (m, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.11 (s, 2H), 4.99 (s, 2H), 4.10-4.08 (m, 4H), 3.96-3.94 (m, 2H), 3.89-3.87 (m, 2H), 3.30 (s, 6H), 1.67 (s, 2H), 1.31 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.24, 155.97, 142.97, 135.53, 135.03, 132.80, 129.60, 129.04, 127.70, 127.26, 122.50, 119.71, 115.44, 113.61, 70.02, 69.56, 68.75, 66.86, 65.35, 62.48, 56.94, 50.40, 37.98, 32.32, 31.78, 31.66. HRMS m / z: [M-Br]+calcd. for C34H47NO3Br+: 598.2714, found 598.2731. Experimental procedure for the preparation of JHSW-m-49 (4-((3-Fluorobenzyl)oxy)phenyl)methanol (85). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 85 was prepared from 1- (bromomethyl)-3-fluoro-benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 85 as a white solid (80% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.37-7.33 (m, 1H), 7.28 (d, J = 8.0 Hz, 2H), 7.21-7.14 (m, 2H), 7.04-6.99 (m, 1H), 6.94 (d, J = 8.0 Hz, 2H), 5.06 (s, 2H), 4.61 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H14O2F+: 233.0978, found 233.0982. 1-((4-(Bromomethyl)phenoxy)methyl)-3-fluorobenzene (86). Following the procedure for the prepar-ation of 1-(bromomethyl) -4-(4-chlorobutoxy)benzene (48), compound 86 was prepared from (4-((3-fluorobenzyl)oxy)phenyl)methanol (85) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 86 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3-Fluorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-49). Following the procedure for the preparation of JHSW-m-01, JHSW-m-49 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2) (0.5 mmol) and 1-((4- (bromomethyl)phenoxy)methyl)-3-fluorobenzene (86) (0.75 mmol) to give JHSW-m-49 as a light yellow oil (70% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.38-7.32 (m, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.19-7.11 (m, 2H), 7.05-7.00 (m, 1H), 6.96 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.05 (s, 2H), 4.97 (s, 2H), 4.11-4.09 (m, 4H), 3.98-3.95 (m, 2H), 3.90-3.87 (m, 2H), 3.29 (s, 6H), 1.67 (s, 2H), 1.32 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.53 (d, J = 257.0 Hz), 160.29, 155.95, 143.04, 138.85, 134.98, 130.32 (d, J = 8.1 Hz), 127.29, 122.82, 119.56, 119.19, 115.23(d, J = 37.3 Hz), 114.28 (d, J = 22.2 Hz), 113.59, 70.03, 69.30, 66.84, 65.35, 62.57, 56.94, 53.45, 50.38, 38.00, 32.33, 31.78, 31.65. HRMS m / z: [M-Br]+calcd. for C34H47NO3F+: 536.3535, found 536.3565. Experimental procedure for the preparation of JHSW-m-50 (4-((3-Chlorobenzyl)oxy)phenyl)methanol (87). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 87 was prepared from 1- (bromomethyl)-3-chloro benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 87 as a white solid (85% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.44-7.43 (m, 1H), 7.31-7.27 (m, 5H), 6.94 (d, J = 8.0 Hz, 2H), 5.04 (s, 2H), 4.61 (s, 2H). HRMS m / z: [M+H]+calcd. for C14H14O2Cl+: 249.0682, found 249.0702. 1-((4-(Bromomethyl)phenoxy)methyl)-3-chlorobenzene (88). Following the procedure for the prepara-tion of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 88 was prepared from (4-((3-chlorobenzyl)oxy)phenyl)methanol (87) (4 mmol) and PBr3(4 mmol) in anhydrous dichloromethane (4 mL) to give 88 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3-Chlorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2- yl)phenoxy)ethoxy)-ethanaminium bromide (JHSW-m-50). Following the procedure for the preparation of JHSW-m-01, JHSW-m-50 was prepared from N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2) (0.5 mmol) and 1-((4- (bromomethyl)phenoxy)methyl)-3-chlorobenzene (88) (0.75 mmol) to give JHSW-m-50 as a light yellow oil (73% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 2H), 7.41-7.40 (m, 1H), 7.32-7.28 (m, 3H), 7.23 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.02 (s, 2H), 4.99 (s, 2H), 4.10-4.08 (m, 4H), 3.96-3.94 (m, 2H), 3.89-3.87 (m, 2H), 3.30 (s, 6H), 1.67 (s, 2H), 1.31 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.23, 155.97, 142.99, 138.32, 135.03, 134.64, 130.02, 128.39, 127.47, 127.27, 125.45, 119.70, 115.38, 113.61, 70.02, 69.27, 68.71, 66.86, 65.34, 62.50, 56.94, 50.39, 37.99, 32.33, 31.78, 31.65. HRMS m / z: [M- Br]+calcd. for C34H47NO3Cl+: 552.3239, found 552.3257. Experimental procedure for the preparation of JHSW-m-51 (4-((3,4-Difluorobenzyl)oxy)phenyl)methanol (89). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl)methanol (47), compound 89 was prepared from 4- (bromomethyl)-1,2-difluoro-benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 89 as a white solid (80% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.31-7.28 (m, 2H), 7.27-7.24 (m, 1H), 7.20-7.11 (m, 2H), 6.95-6.92 (m, 2H), 5.04 (s, 2H), 4.61 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H13O2F2+: 251.0884, found 251.0912. 4-((4-(Bromomethyl)phenoxy)methyl)-1,2-difluorobenzene (90). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 90 was prepared from (4-((3,4-difluorobenzyl)oxy)phenyl)methanol (89) (4 mmol) and PBr3(4 mmol) in anhydrous dichloro-methane (4 mL) to give 90 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3,4-Difluorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium bromide (JHSW-m-51). Following the procedure for the preparation of JHSW-m-01, JHSW-m-51 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)-ethanamine (2) (0.5 mmol) and 4-((4- (bromomethyl)phenoxy)methyl)-1,2-difluorobenzene (90) (0.75 mmol) to give JHSW-m-51 as a light yellow oil (81% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 2H), 7.24-7.22 (m, 3H), 7.17-7.12 (m, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 5.01 (s, 2H), 4.99 (s, 2H), 4.09-4.08 (m, 4H), 3.94-3.93 (m, 2H), 3.88-3.86 (m, 2H), 3.30 (s, 6H), 1.67 (s, 2H), 1.30 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.06, 155.97, 150.48 (dd, J = 247.5, 12.0 Hz), 150.15 (dd, J = 247.2, 12.2 Hz), 142.99, 135.07, 133.31, 127.26, 123.43 (dd, J = 3.0, 4.0 Hz), 119.86, 117.53 (d, J = 18.0 Hz), 116.53 (d, J = 18.0 Hz),, 115.34, 113.60, 70.01, 68.82, 66.87, 65.32, 62.46, 60.40, 56.93, 50.38, 37.98, 32.32, 31.77, 31.64. HRMS m / z: [M-Br]+calcd. for C34H46NO3F2+: 554.3440, found 554.3484. Experimental procedure for the preparation of JHSW-m-52 (4-((3,4-Dichlorobenzyl)oxy)phenyl)methanol (91). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 91 was prepared from 4- (bromomethyl)-1,2-dichloro-benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 91 as a white solid (87% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 4.0 Hz, 1H), 7.45-7.42 (m, 2H), 7.31-7.28 (m, 2H), 6.95-6.91 (m, 2H), 5.01 (s, 2H), 4.61 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H13O2Cl2+: 283.0293, found 283.0321. 4-((4-(Bromomethyl)phenoxy)methyl)-1,2-dichlorobenzene (92). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 92 was prepared from (4-((3,4-dichlorobenzyl)oxy)phenyl)methanol (91) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloro-methane (4 mL) to give light yellow oil. The material was used in the next step without further purification. N-(4-((3,4-Dichlorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium bromide (JHSW-m-52). Following the procedure for the preparation of JHSW-m-01, JHSW-m-52 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2) (0.5 mmol) and 4-((4- (bromomethyl)phenoxy)methyl)-1,2-dichlorobenzene (92) (0.75 mmol) to give JHSW-m-52 as a light yellow oil (78% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 2H), 7.51 (m, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.23 (m, 3H), 6.94 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.00 (m, 4H), 4.11- 4.08 (m, 4H), 3.95 (m, 2H), 3.90-3.87 (m, 2H), 3.30 (s, 6H), 1.68 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.05, 155.95, 143.04, 136.51, 135.09, 132.91, 132.30, 130.72, 129.31, 127.29, 126.62, 119.84, 115.38, 113.60, 70.06, 68.78, 68.66, 66.88, 65.39, 62.61, 56.94, 50.51, 38.00, 32.33, 31.79, 31.66. HRMS m / z: [M-Br]+calcd. for C34H46NO3Cl2+: 586.2850, found 586.2872. Experimental procedure for the preparation of JHSW-m-53 (4-((3,4-Dibromobenzyl)oxy)phenyl)methanol (93). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl)methanol (47), compound 93 was prepared from 1,2- dibromo-4-(bromomethyl) benzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 93 as a white solid (78% isolated yield).1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 2.0 Hz, 1H), 7.47-7.40 (m, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 5.07 (s, 2H), 4.62 (d, J = 4.0 Hz, 2H). HRMS m / z: [M+H]+calcd. for C14H13O2Br2+: 372.9262, found 372.9288. 1,2-Dibromo-4-((4-(bromomethyl)phenoxy)methyl)benzene (94). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 94 was prepared from (4-((3,4-dibromobenzyl)oxy)phenyl)methanol (93, 4 mmol) and PBr3 (4 mmol) in anhydrous dichloro-methane (4 mL) to give 94 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3,4-Dibromobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium bromide (JHSW-m-53). Following the procedure for the preparation of JHSW-m-01, JHSW-m-53 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy) ethan-1-amine (2) (0.5 mmol) and 1,2- dibromo-4-((4-(bromomethyl)phenoxy)methyl)benzene (94) (0.75 mmol) to give JHSW-m- 53 as a light yellow oil (70% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 4.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.44 (m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.04 (s, 2H), 5.00 (s, 2H), 4.10-4.08 (m, 4H), 3.95 (m, 2H), 3.89-3.88 (m, 2H), 3.30 (s, 6H), 1.67 (s, 2H), 1.31 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 159.95, 155.96, 154.16, 142.99, 135.10, 134.70, 130.91, 130.07, 127.27, 122.89, 122.37, 119.95, 115.39, 113.60, 70.03, 68.97, 68.68, 66.86, 65.35, 62.52, 56.94, 50.43, 37.99, 32.33, 31.79, 31.66. HRMS m / z: [M-Br]+calcd. for C34H46NO3Br2+: 676.1819, found 676.1837. Experimental procedure for the preparation of JHSW-m-54 (4-((3-Bromo-2-fluorobenzyl)oxy)phenyl)methanol (95). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 95 was prepared from 1-bromo-3-(bromomethyl)-2-fluorobenzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 95 as a white solid (68% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.65-7.63 (m, 1H), 7.35-7.28 (m, 3H), 7.12 (m, 1H), 6.93 (d, J = 8.0 Hz, 2H), 5.00 (s, 2H), 4.62 (s, 2H). HRMS m / z: [M+H]+calcd. for C14H13O2BrF+: 311.0083, found 311.0114. 1-Bromo-3-((4-(bromomethyl)phenoxy)methyl)-2-fluorobenzene (96). Following the procedure for the preparation of 1-(bromomethyl) -4-(4-chlorobutoxy)benzene (48), compound 96 was prepared from (4-((3-bromo-2-fluorobenzyl)oxy)phenyl)methanol (95) (4 mmol) and PBr3(4 mmol) in anhydrous dichloro-methane (4 mL) to give 96 as a light yellow oil. The material was used in the next step without further purification. N-(4-((4-Bromo-3-fluorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phen-oxy)ethoxy)ethanaminium bromide (JHSW-m-54). Following the procedure for the preparation of JHSW-m-01, JHSW-m-54 was prepared from N,N- dimethyl-2-(2-(4-(2,4,4-trimethylpentan-2-yl)-phenoxy)ethoxy)ethanamine (2) (0.5 mmol) and 1-bromo-3-((4-(bromomethyl)phenoxy)methyl)-2-fluorobenzene (96) (0.75 mmol) to give JHSW-m-54 as a light yellow oil (73% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.64-7.61 (dd, J = 8.0, 4.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.34-7.31 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.13 (t, J = 4.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 4.99 (s, 4H), 4.11-4.08 (m, 4H), 3.96-3.98 (m, 2H), 3.89-3.87 (m, 2H), 3.30 (s, 6H), 1.68 (s, 2H), 1.31 (s, 6H), 0.69 (s, 9H).13C NMR (100 MHz, CDCl3) δ 158.89 (d, J = 245 Hz), 155.95, 153.32, 143.03, 135.05, 133.72, 132.66, 129.43, 128.14 (d, J = 7 Hz), 127.28, 119.77, 116.7 (d, J = 22 Hz), 115.36, 113.59, 70.03, 68.68, 66.85, 65.33, 62.51, 60.06, 56.93, 50.40, 37.99, 32.33, 31.79, 31.66. HRMS m / z: [M-Br]+calcd. for C34H46NO3BrF+: 614.2640, found 614.2688. Experimental procedure for the preparation of JHSW-m-55 (4-((3-Bromo-4-fluorobenzyl)oxy)phenyl)methanol (97). Following the procedure for the preparation of (4-(4-chlorobutoxy)phenyl) methanol (47), compound 97 was prepared from 2-bromo-4-(bromomethyl)-1-fluorobenzene (24.2 mmol) and 4-hydroxybenzyl alcohol (12.1 mmol) to give 97 as a white solid (77% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.54-7.50 (m, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.05 (t, J = 4.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 5.15 (s, 2H), 4.62 (s, 2H). HRMS m / z: [M+H]+calcd. for C14H13O2BrF+: 311.0083, found 311.0114. 2-Bromo-4-((4-(bromomethyl)phenoxy)methyl)-1-fluorobenzene (98). Following the procedure for the preparation of 1-(bromomethyl)-4-(4-chlorobutoxy)benzene (48), compound 98 was prepared from (4-((3-bromo-4-fluorobenzyl)oxy)phenyl)methanol (97) (4 mmol) and PBr3 (4 mmol) in anhydrous dichloro-methane (4 mL) to give 98 as a light yellow oil. The material was used in the next step without further purification. N-(4-((3-Bromo-4-fluorobenzyl)oxy)benzyl)-N,N-dimethyl-2-(2-(4-(2,4,4- trimethylpentan-2-yl)phenoxy) ethoxy)ethanaminium bromide (JHSW-m-55). Following the procedure for the preparation of JHSW-m-01, JHSW-m-54 was prepared from N,N-dimethyl- 2-(2-(4-(2,4,4-trimethylpentan-2-yl)-phenoxy)ethoxy)ethanamine (2, 0.5 mmol) and 2-bromo- 4-((4-(bromomethyl)phenoxy)methyl)-1-fluorobenzene (98, 0.75 mmol) to give JHSW-m-54 as a light yellow oil (78% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 2H), 7.55-7.51 (m, 1H), 7.44-7.40 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.07-7.03 (m, 1H), 6.96 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 5.12 (s, 2H), 5.00 (s, 2H), 4.11-4.08 (m, 4H), 3.97-3.95 (m, 2H), 3.90-3.87 (m, 2H), 3.30 (s, 6H), 1.68 (s, 2H), 1.31 (s, 6H), 0.68 (s, 9H).13C NMR (100 MHz, CDCl3) δ 161.03 (d, J = 242.0 Hz), 160.08, 155.96, 143.00, 135.05, 133.54, 128.76, 127.28, 125.37 (d, J = 5.0 Hz), 125.14 (d, J = 15.2 Hz), 119.86, 115.33, 113.59, 112.85 ((d, J = 12 Hz), 70.03, 66.85, 65.34, 63.83, 62.51, 56.94, 53.46, 50.41, 37.99, 32.33, 31.78, 31.65. HRMS m / z: [M-Br]+calcd. for C34H46NO3BrF+: 614.2640, found 614.2688. Experimental procedure for the preparation of JHSW-m-56 N-(4-((3-Bromobenzyl)oxy)benzyl)-2-(2-(2,4-di-tert-butylphenoxy)ethoxy)-N,N- dimethylethanaminium bromide (JHSW-m-56). Following the procedure for the preparation of JHSW-m-01, JHSW-m-56 was prepared from 2-(2-(2,4-di-tert-butylphenoxy)ethoxy)- N,N-dimethylethan-1-amine (28) (0.5 mmol) and 1-bromo-3-((4- (bromomethyl)phenoxy)methyl)benzene (64) (0.75 mmol) to give JHSW-m-56 as a light yellow oil (71% isolated yield). 1H NMR (400 MHz, CDCl3) δ 7.58-7.56 (m, 3H), 7.47-7.44 (m, 1H), 7.34-7.31 (m, 1H), 7.30 (d, J = 4.0 Hz, 1H), 7.25 (m, 1 H), 7.16-7.13 (m, 1H), 6.94 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 5.01 (s, 2H), 4.99 (s, 2H), 4.13-4.07 (m, 4H), 3.96-3.91 (m, 4H), 3.29 (s, 6H), 1.34 (s, 9H), 1.28 (s, 9H).13C NMR (100 MHz, CDCl3) δ 160.25, 154.97, 143.19, 138.55, 137.16, 135.00, 131.34, 130.40, 130.30, 125.95, 124.06, 123.49, 122.80, 119.59, 115.40, 111.55, 70.73, 69.22, 68.77, 66.71, 65.29, 62.64, 50.40, 35.06, 34.30, 31.58, 29.96. HRMS m / z: [M-Br]+calcd. for C34H47NO3Br+: 677.1907, found 677.1953. Exemplary Biological Activity of Compounds of the Disclosure The mitochondria are central to tumor metabolism, integrating both cellular bioenergetic and biosynthetic metabolism, which are required for tumor initiation and maintenance. Due to a lack of in vivo imaging probes there is a gap in our knowledge at a physiological and mechanistic level of how mitochondrial bioenergetics are regulated in NSCLC. To address this gap, functionally imaged mitochondrial activity in lung tumors was developed utilizing the PET imaging tracer 4-[18F]fluorobenzyl-triphenylphosphonium (18F- BnTP). Based on the findings in this work,18F-BnTP is shown to be an in vivo biomarker of mitochondrial membrane potential (ΔΨ) and oxidative phosphorylation (OXPHOS) in lung tumors. Using18F-BnTP mitochondrial activity in lung tumors were profiled. Furthermore, this work has demonstrated that uptake of the18F-BnTP tracer is effective in distinguishing lung tumors with both high and low ΔΨ. It was next sought to exploit OXPHOS and ΔΨ in therapy-resistant KRAS / LKB1 mutant lung tumors that have been identified as having unique sensitivities to mitochondrial inhibitors. As therapies targeting cancer metabolism enter clinical trials, there is emphasis to identify and target key nodes of cellular metabolism such as mitochondrial inhibitors. Metabolic vulnerabilities in therapy-resistant KRAS / LKB1 mutant lung tumors have been successfully identified and targeted in this work, using the mitochondrial inhibitors phenformin. In addition, as shown in Figure 1, conjugation of the lipophilic cation triphenylphosphonium (TPP) to therapeutics increases the concentration of drug delivered to the mitochondria. The small molecule drug Benzethonium (Benz) that selectively induced apoptosis in KRAS / LKB1 mutant LUADs was identified. Benz is a non-carcinogenic antimicrobial agent that was identified to induce caspase-dependent apoptosis in head and neck squamous cancer cell lines and reduced tumor burden in xenografts. Furthermore, conjugation of TPP to Benz derivatives selectively induces apoptosis in lung tumor cells bearing LKB1 mutations while not affecting normal cells. Mitochondria are required for tumor initiation and maintenance Seminal experiments identified that loss of mtDNA inhibited mitochondrial bioenergetics and suppressed tumor cell growth in cell culture and on xenografts. Deletion of the mitochondrial transcription factor A (tfam) inhibited tumor initiation and progress in an autochthonous KrasG12Ddriven lung tumor model demonstrating an in vivo requirement for mitochondria during tumorigenesis. Conversely, loss of function (LOF) mutations in mitochondrial tricarboxylic cycle (TCA cycle) genes such as succinate dehydrogenase (SDH) and fumarate hydratase (FH) are oncogenic and reversible. These studies demonstrate how gain or loss of mitochondrial function can either promote or suppress tumorigenesis. KRAS / LKB1 mutant LUADs are immune cold but metabolically active tumors. Clinical evidence has shown LUADs with co-mutations in KRAS and LKB1 genes (KRAS / LKB1) are highly unresponsive to PD-(L)1 checkpoint blockade and are defined as immune cold. This underscores the need to identify alternative vulnerabilities that can be targeted in this large subset of lung tumors. Loss of function mutations in the LKB1 tumor suppressor gene are common events in LUAD and LKB1 is frequently co-mutated with KRAS. Importantly, KRAS / LKB1 mutant lung tumors have been defined as metabolically active. LKB1 inactivation results in hyper-activation of the mTORC1 pathway, which promotes metabolic reprogramming of cancer cells to a glycolytic metabolic phenotype that is dependent upon mTORC1 and HIF1α. KRAS / LKB1 mutant LUADs are selectively sensitive to mitochondrial inhibition. In tumor cells defective for LKB1, metabolic and mitochondrial stress are not appropriately sensed and energy homeostasis is not efficiently restored through deregulation of the AMPK pathways. This provides an Achilles heel to target the mitochondria in LKB1 mutant cells. Specifically, LKB1-deficient tumor cells are unable to respond to energy stress due to loss of AMPK signaling and selectively undergo increased apoptosis following treatment with mitochondria inhibitors (MIs) the biguanide phenformin or Benz, and a therapeutic benefit for using MIs in the treatment of cancer has been demonstrated. Importantly, identifying compounds that selectively induce apoptosis in LKB1 mutant tumors remain an important and unmet clinical challenge. Utilizing18F-BnTP PET as a companion diagnostic to guide the delivery of TPP conjugated mitochondrial inhibitors to KRAS / LKB1 mutant lung tumors. Studies of mitochondria in cancer have historically relied upon cell culture systems to measure mitochondrial function, underscoring the need to develop probes to measure mitochondrial function in vivo. In order to bridge this knowledge gap the PET tracer,18F-BnTP, that functions as a biomarker of mitochondrial bioenergetics was developed. Accumulation of18F-BnTP is on the mitochondrial membrane potential (ΔΨ), which drives oxidative phosphorylation (OXPHOS). Therefore, using18F-BnTP, lung tumors with high ΔΨ can be identified. The mitochondrial inhibitor Benzethonium was thus conjugated to Triphenylphosphonium (TPP) to generate TPP conjugated Benz compounds that localize to the mitochondria and selectively kill KRAS / LKB1 mutant lung tumors. It is proposed that18F- BnTP PET will effectively identify KRAS / LKB1 mutant lung tumors with high ΔΨ that can be selectively targeted with TPP-Benz. Triphenylphosphonium (TPP) conjugated OXPHOSi’s. Results 18F-BnTP PET measures mitochondrial bioenergetics and OXPHOS-dependent metabolism in vivo. 18F-BnTP tracer was synthesized and examined to assess its function as a biomarker of mitochondrial bioenergetics in lung tumors in vivo. The uptake and retention of18F-BnTP into the mitochondria is dependent upon the ΔΨ shown in Figure 3A. Pharmacological inhibition of the electron transport chain (ETC) with Complex I inhibitors leads to decreased ΔΨ and concomitant decreased uptake of18F-BnTP into tumor cells. It was identified that tumors from Kras / Lkb1 mutant LUADs from GEMMs had significantly higher18F-BnTP uptake and Complex I activity than lung squamous cell carcinomas (LUSC) (Figs.3B, 3D) suggesting that ΔΨ and Complex I activity may be predictive of response or resistance to Complex I inhibition.18F-BnTP uptake in syngeneic mice TT implanted with mouse OXPHOSHILUAD cells was then measured following acute 4 hour treatment with either oligomycin or rotenone (Fig.3D). A safely tolerated dose of rotenone (0.5 mg / kg) or oligomycin (0.25 mg / kg) that is below the toxic dose range was used.18F-BnTP uptake in lung tumors was significantly increased after delivery of oligomycin whereas rotenone treatment significantly reduced18FBnTP uptake (Fig. 3E). The results demonstrate that18F-BnTP PET detected acute changes in ΔΨ in lung tumors following inhibition of respiratory Complexes I or V. A synthetic lethal chemical screen identified OXPHOSi’s that selectively induce apoptosis in KRAS / LKB1 mutant NSCLC. Small molecule OXPHOSi’s from published screen(s) were selected and tested them in a 96 or 384 well plate multiplexed HTS we developed (Fig.4A). The purpose of the screen is to first identify FDA approved OXPHOSi’s in the literature and screen for compounds that inhibit ΔΨ and OXPHOS while selectively inducing apoptosis in cancer cell lines. Second, the screen will validate lead compounds in vivo using GEMMs. Benz was successfully identified as a lead compound that inhibited ΔΨ in KRAS / LKB1 mutant human and mouse lung tumor cell lines (Fig. 4B). Benz is a non-carcinogenic antimicrobial agent that was identified to induce caspase-dependent apoptosis in head and neck squamous cancer cell lines and reduced tumor burden in xenografts. Benz is potent at low doses and has an IC50of 500nM, selectively induced apoptosis and inhibited OXPHOS in KRAS / LKB1 mutant NSCLC cells (Figs.4C-E). These data show that LKB1 inactivation sensitizes lung tumors to energetic stress and OXPHOS inhibition. Three clinically relevant biomarkers of apoptosis, energy and mitochondrial stress – cleaved caspase 3 (CC3), phospho-AMPKαThr172 (p-AMPKα) and mitochondrial heat shock protein GRP78 by immunoblot and IHC were identified and validated. Lastly, Benz was identified to significantly inhibit cell viability in a panel of KRAS / LKB1 mutant NSCLC tumor lines (Fig.4F). Identification of TPP-Benz derivatives that selectively induce apoptosis in human and mouse KRAS / LKB1 mutant LUAD cells. 46 TPP conjugated Benzethonium (TPP-Benz) derivatives were synthesized and are described as compounds JHSW-01 – m11 (Fig.5A). Cell viability in KrasG12D; p53- / -(KP) and KrasG12D; p53- / -;Lkb1- / -(KPL) mouse lung tumors cell lines treated with TPP-Benz derivatives as compared to vehicle, Benz or Phenformin were measured. Initial screen identified 12 TPP- Benz derivatives that inhibited cell viability similar to Benz (Fig. 5A). It was next sought to identify TPP-Benz derivatives that met two criteria: 1) selective induction of apoptosis in LKB1 mutant lung tumor cell lines and 2) induce minimal to no toxicity in normal cell lines. Apoptosis in the LKB1 mutant KPL cell line was examined as compared to the KP and the normal wildtype mouse embryonic fibroblast cell line MEF17.4 potential lead compounds that met these criteria were identified – JHSWm03, m04 and m06, and m11 shown in Fig.5B. The lead TPP-Benz compounds were next examined on normal human bronchiole epithelial cells (HBECs) and the liver cell line AML1. JHSW-08 was identified to show increased cytotoxicity in the AML1 cell lines while both JHSW-m06 and m11 showed no toxicity above that of vehicle (Figs.5C, 5D). JHSW compounds bind to the Mitochondrial Calcium Uniporter (MCU). The MCU is localized in the mitochondrial inner matrix as described in FIG.6A and regulates the influx of Ca2+into the inner mitochondrial membrane (IMM). The Cellular Thermal Shift Assay (CETSA) represents a test to selective binding of a small molecule to a specific protein. It works by measuring protein stability or resistance to heat mediated degradation upon binding of a small molecule drug to a selective protein. If the small molecule binds to a protein, then it will render that protein resistant to heat mediated degradation. CETSA analysis demonstrates that JHSW compounds bind to the MCU channel subunits and stabilize its degradation at high temperatures (FIG.6B). JHSW mediated tumor cell death is dependent on high expression the MCU Regulatory 1 subunit. It was identified that tumor cells with high protein expression of the MCU Regulatory 1 (MCUR1) subunit are highly sensitive to JHSW analogs shown in FIGs.7A-7C). To confirm this, CRISPR mediated knockdown of MCUR1 in MCUR1 high expressing H1703 cells was performed (FIG.7D) and it was demonstrated that MCUR1 knockdown (KD) prevented JHSW induced cell death in H1703 lung cancer cells as compared to cell expressing MCRU1 (FIG. 7E). Next, the converse experiment was performed and MCUR1 (MCUR1 OE) was overexpressed in JHSW-resistant H2170 (MCUR1LO) lung cancer cells to determine if MCUR1 overexpression sensitized cells to JHSW (FIG. 7F). It was demonstrated that overexpression of MCUR1 sensitizes H2170 cell lines to JHSW 29 and 34 analogs (FIG.7G) thus confirming that JHSW mediated cell death is dependent on MCUR1 expression. JHSW compounds inhibit Ca2+ flux into the mitochondrial inner membrane in an MCUR1-dependent manner. It was next evaluated whether the JHSW compounds inhibit or stimulate Ca2+flux into the inner mitochondrial membrane (IMM). To test this, the Mitycam Ca2+flux reporter system was used, which is localized to the IMM and emits fluorescent light upon Ca2+binding to it. It is used to measure Ca2+influx into the IMM following stimulation with caffeine. JHSW compounds were demonstrated to inhibit Ca2+flux into the IMM in MCUR1 high expressing H1703 cells but not in MCUR1 low expressing H2170 cells (FIGs. 3A-3B). These results demonstrate that JHSW compounds inhibit Ca2+flux into the mitochondria in MCUR1HIexpressing tumor cells as compared to MCUR1LOexpressing tumor cells. MCUR1 is highly expressed in most cancers compared to healthy tissue. Pan cancer analysis of MCUR1 gene expression identified that MCUR1 is highly expressed in most cancers compared to matched healthy tissue (FIG. 9A). The database includes 56,938 unique samples: from GEO, GTex, TCGA, and TARGET databases. This includes 15,648 normal, 40,442 tumor, and 848 metastasis samples. The pan-cancer analysis displays the expression range for a selected gene across all tissues using RNA Seq data from normal and cancer tissues. The data showed that MCUR1 gene expressions were higher in tumor than in normal tissues except in skin and renal tissues. Further differential MCUR1 gene expression analysis in subtypes of Non-Small Cell Lung Cancer (NSCLC) demonstrated that MCUR1 has significantly higher expression in NSCLC subtypes that include lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) as compared to healthy lung tissue (FIGs.9B-9C). Protein analysis in tumors identified high MCUR1 expression lung tumor subtypes – LUAD and LUSC as well as other cancers including small cell lung cancer (SCLC), Breast and Bladder cancers (FIGs. 9D-9F). Protein levels of MCU remained relatively constant in all samples and vinculin was used as a loading control. INCORPORATION BY REFERENCE All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control. EQUIVALENTS While specific embodiments of the subject invention have been discussed, the above specification is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon review of this specification and the claims below. The full scope of the invention should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations.

Claims

CLAIMS We claim:

1. A compound having a structure represented by Formula (I):Formula (I) wherein, A1and A2are each independently alkyl, aryl, or heteroaryl; each R1and R2is independently selected from alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, haloalkyl, hydroxyl, hydroxyalkyl, carboxyl, carbonate, acyl, acyloxy, ester, thioester, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, amino, aminoalkyl, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido; L1and L2are each independently alkyl, alkoxy, alkoxyalkyl, oxyalkyloxyalkyl, oxyalkylaminoalkyl, oxyalkylthioalkyl, aminoalkylaminoalkyl, aminoalkylthioalkyl, thioalkylaminoalkyl, or thioalkylthioalkyl; Raand Rbare each independently selected from H, alkyl, or aralkyl; Z- is an anion; n and m are each independently 0, 1, 2, 3, 4, or 5; and q is 1 or 2.

2. The compound of claim 1, wherein A1is aryl.

3. The compound of claim 1 or 2, wherein R1is alkyl.

4. The compound of any one of claims 1-3, wherein A1is phenyl.

5. The compound of any one of claims 1-4, wherein R1is trimethylpentyl.

6. The compound of any one of claims 1-5, wherein the compound has a structure represented by Formula (Ia):(Ia).

7. The compound of any one of claims 1-6, wherein L1is O(CH2)x1(O)y1(CH2)z1 and x1, y1, and z1are each independently 0, 1, 2, 3, 4, or 5.

8. The compound of any one of claims 1- 7, wherein x1is 2, y1is 1, and z1is 2.

9. The compound of any one of claims 1-7, wherein x1 is 3, y1 is 1, and z1 is 2.

10. The compound of any one of claims 1-7, wherein x1 is 3, y1 is 1, and z1 is 3.

11. The compound of any one of claims 1-7, wherein x1is 1, y1is 0, and z1is 1.

12. The compound of any one of claims 1-11, wherein Raand Rbare each alkyl.

13. The compound of any one of claims 1-11, wherein Raand Rbare each methyl or ethyl.

14. The compound of any one of claims 1-11, wherein Rais alkyl (e.g., methyl) and Rbis aralkyl (e.g., benzyl).

15. The compound of any one of claims 1-7, or 8, wherein the compound has a structure represented by Formula (Ib):

16. The compound of any one of claims 1-7, or 8, wherein L2is alkyl.

17. The compound of any one of claims 1-7, or 8, wherein A2is aryl.

18. The compound of any one of claims 1-7, or 8, wherein A2is phenyl.

19. The compound of any one of claims 1-7, 8, or 12-13, wherein the compound has a structure represented by Formula (Ic):(Ic).

20. The compound of any one of claims 1-19, wherein R2is alkoxy (e.g., butoxy).

21. The compound of any one of claims 1-19, wherein R2is arylalkoxy (e.g., phenyl ethyloxy).

22. The compound of any one of claims 1-19, wherein R2is (cycloalkyl)alkoxy (e.g., cyclohexylmethoxy.

23. The compound of any one of claims 1-19, wherein R2is carbonate.

24. The compound of any one of claims 1-19, wherein R2is hydroxyl.

25. The compound of any one of claims 1-19, wherein R2is nitro.

26. The compound of any one of claims 1-19, wherein R2is halo.

27. The compound of any one of claims 1-19, wherein R2is acyloxy.

28. The compound of any one of claims 1-19 wherein R2is substituted with at least one R3, wherein each R3is independently alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, hydroxyl, hydroxyalkyl, carboxyl, acyl (e.g., acetyl), ester, thioester, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, amino, aminoalkyl, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido.

29. The compound of any one of claims 1-19, 23, or 28, wherein R3is halo (e.g., bromo).

30. The compound of any one of claims 1-19, or 28, wherein R3is hydroxyalkyl.

31. The compound of any one of claims 1-19, or 28, wherein R3is alkyl (e.g., t-butyl).

32. The compound of any one of claims 1-19, or 28, wherein R3is heteroaryl (e.g., pyridiniumyl or triazolyl).

33. The compound of any one of claims 1-20 or 28, wherein R3is heterocyclyl (e.g., dioxanyl).

34. The compound of any one of claims 1-20 or 28, wherein R3is cyano.

35. The compound of any one of claims 1-20 or 28, wherein R3is aralkoxy (e.g., benzyloxy).

36. The compound of any one of claims 1-20 or 28, wherein R3is arylacyl (e.g., phenylacyl).

37. The compound of claim 36, wherein R3is further substituted with heterocyclyl (e.g., pyrolidinyl).

38. The compound of any one of claims 1-28, wherein R3is phosphoryl (e.g., triphenylphosphonium, tricyclohexylphosphonium, tritolylphosphonium, trimethoxyphenylphosphonium, diphenylmethylphosphonium, or dimethylphenylphosphonium).

39. The compound of any one of claims 1-18, wherein the compound has a structure represented by Formula (Id):wherein R2is independently selected from alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, hydroxyl, hydroxyalkyl, carboxyl, carbonate, acyl (e.g., acetyl), acyloxy, alkoxy, (cycloalkyl)alkoxy, arylalkoxy, alkylthio, phosphoryl, aminoalkyl, amido, cycloalkyl, or heterocyclyl; Rcand Rdare each independently H, alkyl, aralkyl; L3is alkyl, alkoxy, alkoxyalkyl, or oxyalkyloxyalkyl; R4is independently alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, aryl, heteroaryl, halo, hydroxyl, hydroxyalkyl, carboxyl, acyl (e.g., acetyl), ester, thioester, alkoxy, cycloalkoxy, arylalkoxy, alkylthio, phosphoryl, amino, aminoalkyl, amido, cyano, nitro, azido, cycloalkyl, heterocyclyl, alkylsulfoxidyl, alkylsulfonyl, arylacyl, or sulfonamido; i is 0, 1, 2, 3, 4, or 5.

40. The compound of claim 39, wherein R2is alkyl.

41. The compound of claim 39 or 40, wherein Rcand Rdare each alkyl.

42. The compound of claim 41, wherein Rcand Rdare each methyl.

43. The compound of any one of claims 39-42, wherein L3is O(CH2)x2(O)y2(CH2)z2 and x2 y2, and z2 are each independently 0, 1, 2, 3, 4, or 5.

44. The compound of any one of claims 39- 43, wherein x2is 1, y2is 0, and z2is 1.

45. The compound of any one of claims 39-43, wherein x2 is 2, y2 is 1, and z2 is 2.

46. The compound of any one of claims 39-43, wherein x2 is 3, y2 is 1, and z2 is 3.

47. The compound of any one of claims 39-46, wherein R4is alkyl.

48. The compound of any one of claims 39-47, wherein R4is trimethylpentyl.

49. A compound selected from:,,,JHSW-11 ,,,,,,,,,,,, ,,,50. A pharmaceutical composition comprising the compound of any one of claims 1-49 and a pharmacetically acceptable excipient.

51. A method of treating a disease or disorder characterized by a mutation in KRAS in a subject in need thereof, comprising administering a compound of any one of claims 1-49 to the subject.

52. The method of claim 51, wherein the disease or disorder is further characterized by a mutation in LKB1.

53. A method of treating a disease or disorder characterized by a mutation in LKB1 in a subject in need thereof, comprising administering a compound of any one of claims 1-49 to the subject.

54. The method of claim 53, wherein the disease or disorder is further characterized by a mutation in KRAS.

55. The method of any one of claims 51-55, wherein the disease or disorder is cancer.

56. The method of claim 56, wherein the cancer is lung cancer.

57. The method of claim 57, wherein the cancer is non-small cell lung cancer.

58. A method of treating cancer in a subject in need thereof, comprising administering a compound of any one of claims 1-49 to the subject.

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