A method for synthesizing amino acid and amino alcohol compounds

Abstract

This invention provides a method for synthesizing amino acids and amino alcohols, comprising the following steps: mixing a cyclic amine compound, a photocatalyst, and a base, and then adding a reducing agent and a solvent under a CO2 atmosphere to obtain a reaction solution; or mixing a cyclic amine compound, a photocatalyst, and a base, and then adding a reducing agent, an aldehyde / ketone compound, and a solvent under a N2 atmosphere to obtain a reaction solution; stirring the resulting reaction solution under light and room temperature conditions for 0.1–100 h, and then acidifying and purifying the reaction product to obtain amino acids or amino alcohols; this synthesis method can effectively solve the problem of the lack of research on the C-N bond functionalization reaction of cyclic amine compounds involving visible light catalysis of carbon dioxide or aldehydes and ketones in the prior art. At the same time, this method has the advantages of convenient operation, inexpensive and readily available raw materials, mild reaction conditions, broad substrate universality, and high product yield.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing amino acids and amino alcohols. Background Technology

[0002] Functionalized amines, such as various non-natural amino acids and amino alcohols, are important physiologically active molecules or material molecules. The reductive ring-opening functionalization reaction of inexpensive, readily available, and widely derived cyclic amines is a crucial pathway to obtaining these high-value functionalized amines. Specifically, cyclic amines, as a class of atypical electrophiles, form highly reactive carbanions through reductive ring-opening and CN-bond cleavage, thus enabling Barbier reactions and the mounting of various electrophiles.

[0003] However, cyclic amines have low reduction potentials, making them generally difficult to reduce. Furthermore, pyrrolidines and piperidines, being unstrained five- and six-membered rings, exhibit slow ring-opening kinetics. Therefore, development in this field has been slow. Moreover, previous reports primarily used strong reducing agents such as elemental lithium, elemental sodium, or thulium diiodide. The use of these metal reducing agents results in harsh reaction conditions, a narrow substrate range, poor functional group compatibility, and safety risks. Achieving the reductive ring-opening functionalization of cyclic amines under mild conditions is a key challenge in this field.

[0004] On the other hand, carbon dioxide (CO2) is a widely available, low-toxicity, and inexpensive greenhouse gas, and also an important C-1 synthon in organic synthesis. Utilizing carbon dioxide as a carboxyl source to achieve CN-bond carboxylation of amines would be a sustainable and environmentally friendly strategy. However, the low reactivity of cyclic amines and CO2 makes the reaction quite challenging. Summary of the Invention

[0005] To address the aforementioned problems in the prior art, this invention provides a method for synthesizing amino acids and amino alcohols. This method is based on the reductive ring-opening functionalization reaction of cyclic amine compounds. This method effectively fills the gap in the research on CN-bond functionalization reactions of cyclic amine compounds using visible light catalysis involving carbon dioxide or aldehydes and ketones. At the same time, this method has the advantages of convenient operation, inexpensive and readily available raw materials, mild reaction conditions, broad substrate applicability, and high product yield.

[0006] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows:

[0007] A method for synthesizing amino acids and amino alcohols includes the following steps:

[0008] A cyclic amine compound, a photocatalyst, and a base were mixed, and then a reducing agent and an organic solvent were added under a CO2 atmosphere to obtain a reaction solution. The reaction solution was stirred under light and room temperature conditions, and then the reaction product was acidified and purified to obtain an amino acid compound.

[0009] Alternatively, a cyclic amine compound, a photocatalyst, and a base can be mixed, and then a reducing agent, an aldehyde / ketone compound, and a solvent can be added under an inert atmosphere to obtain a reaction solution. The reaction solution is stirred under light and room temperature conditions, and then the reaction product is acidified and purified to obtain an amino alcohol compound.

[0010] The general structural formulas of cyclic amine compounds are shown in formula (I), and the general structural formulas of aldehyde / ketone compounds are shown in formula (II):

[0011]

[0012] Where n = 0 to 5; when n = 0, the structure is an aziridine compound; R 1 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, carbonyl, or sulfonyl; R 2 R 3 R 4 and R 5 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, cyano, carboxyl, carbonyl, acyloxy, alkoxy, aryloxy, siloxy, sulfonyloxy, phosphoxy, sulfonyl, hydroxyl, amino, substituted amino, mercapto, thioether, thioester, sulfonic acid, halogen, silyl, or boron; R 6 and R 7 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, cyano, or carbonyl; R 2 R 3 R 4 R 5 R 6 and R 7 They can be the same or different.

[0013] Furthermore, cyclic amine compounds include:

[0014]

[0015]

[0016] Aldehydes / ketones include:

[0017]

[0018] Furthermore, the molar ratio of cyclic amine compound, photocatalyst, base and reducing agent is 1:0.0001~0.5:0.1~10:1~10; the molar ratio of cyclic amine compound, photocatalyst, base, reducing agent and aldehyde / ketone compound is 1:0.0001~0.5:0.1~10:1~10:0.1~10.

[0019] Furthermore, the photocatalyst is an organic dye or an organometallic complex.

[0020] Furthermore, the photocatalyst is a DA-type photocatalyst or an Ir-type photocatalyst.

[0021] Furthermore, the photocatalyst is at least one of 4CzIPN, 4DPAIPN, 3DPAFIPN, 3DPA2FBN, 5CzBN, 4CzPN, DPZ, 4CzPN-Ph, 4CzPN-Bu, 4CzTPN, 4CzTPN-Bu, Ir(dFCF3ppy)2(dtbbpy)PF6, fac-Ir(dF(ppy)3), fac-Ir(ppy)3, and Ir(ppy)2(dtbbpy)PF6.

[0022] Furthermore, the base is a tert-butoxide, carbonate, bicarbonate, fluoride, phosphate, hydrogen phosphate, carboxylate, or organic base.

[0023] Furthermore, tert-butoxide is a KO t Bu, NaO t Bu、LiO t Bu or Ca(O t Bu)2; the carbonate is Cs2CO3, K2CO3, Na2CO3 or Li2CO3; the bicarbonate is CsHCO3, KHCO3 or NaHCO3; the fluoride is CsF, KF, NaF or LiF; the phosphate is K3PO4, Na3PO4 or Li3PO4; the carboxylate is CsOAc, KOAc, NaOAc, CsOPiv, NaOPiv or KOPiv; the organic base is DBU, TBD, DABCO, TMG, DBN, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3 or NET3.

[0024] Furthermore, the reducing agent is an organic amine compound.

[0025] Furthermore, the organic amine compounds include DBU, TBD, DABCO, TMG, DBN, and DIPEA. i Pr2NEt, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3, or NET3.

[0026] Furthermore, the wavelength of the visible light described in S2 is 300–700 nm.

[0027] Furthermore, the solvent is NMP, DMSO, DMF, DMAc, THF, DCM, MeOH, or MeCN; preferably DMAc.

[0028] The reaction formula of this invention is as follows:

[0029]

[0030] Where n = 0 to 5; R 1 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, carbonyl, or sulfonyl; R 2 R 3 R 4 and R 5 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, cyano, carboxyl, carbonyl, acyloxy, alkoxy, aryloxy, siloxy, sulfonyloxy, phosphoxy, sulfonyl, hydroxyl, amino, substituted amino, mercapto, thioether, thioester, sulfonic acid, halogen, silyl, or boron; R 6 and R 7 It can be hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, ester, amide, cyano, or carbonyl; R 2 R 3 R 4 R 5 R 6 and R 7 They can be the same or different.

[0031] The beneficial effects of this invention are as follows:

[0032] 1. This invention provides a method for synthesizing amino acids and amino alcohols. Under visible light catalysis, cyclic amines are used as reaction substrates, and CO2, aldehydes or ketones are used as coupling electrophilic reagents. Photocatalysts, reducing agents and bases are added simultaneously, and the amino acids and amino alcohols are obtained under mild conditions. This method is convenient to operate and uses inexpensive and readily available raw materials.

[0033] 2. The preparation method of the present invention exhibits excellent reactivity for cyclic amines and aldehydes and ketones, realizing the reduction and ring-opening functionalization reaction of cyclic amine compounds. It has the characteristics of mild reaction conditions, broad substrate versatility, and high product yield. Attached Figure Description

[0034] Figure 1 This is a reaction mechanism diagram of the present invention. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0036] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0037] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes the element.

[0038] The features and performance of the present invention will be further described in detail below with reference to the embodiments and accompanying drawings.

[0039] The reaction mechanism of this invention is as follows: Figure 1 As shown, the specific process is as follows: taking 4DPAIPN as a photocatalyst, N-Boc-2-phenylazacyclobutane as a cyclic amine substrate, and CO2 as another electrophilic reagent as an example; firstly, 4DPAIPN is photoexcited to generate 4DPAIPN. * The species was reduced by the reducing agent DIPEA to produce 4DPAIPN. ·- and DIPEA ·+ Furthermore, under the action of light, 4DPAIPN ·- Excitation is 4DPAIPN ·-* The species can reduce cyclic amine substrates with a single electron to generate intermediate A and regenerate 4DPAIPN; intermediate A undergoes CN bond cleavage and ring opening to generate intermediate B, which is then photocatalytically reduced to carbanion C; subsequently, the carbanion attacks CO2, and after acidification, the target amino acid derivative is obtained.

[0040] Example 1

[0041] A method for synthesizing γ-amino acid compounds based on the CN-bond carboxylation of 2-arylazine butane, the specific process of which is as follows:

[0042] After drying a 10 mL Schlenk reaction tube equipped with a stirrer under vacuum, 0.2 mmol of 2-arylazacyclobutane (added at this stage if the substrate is solid; otherwise, added via syringe after the addition of the reducing agent if the substrate is liquid) and photocatalyst 4DPAIPN (2 mol%) were added. The tube was then placed in a glove box, and 1 equivalent of Cs₂CO₃ was added. The tube was then sealed and removed from the glove box. The tube was purged three times under a double-row CO₂ atmosphere. After purging, 2 equivalents of DIPEA (N,N-diisopropylethylamine) and 2 mL of DMAc (ultra-dry solvent) were added under a CO₂ stream. After adding the solvent, the tube was sealed and placed 1 cm away from 30 W blue (wavelength 400–480 nm) LEDs. The tube was stirred at room temperature for 24 h. After the reaction was complete, 2 mL of 2N HCl and 2 mL of ethyl acetate were added and stirred for 2 min. The tube was then extracted five times with ethyl acetate. The organic phases were combined and evaporated to dryness using a rotary evaporator. The solid residue was separated by silica gel column chromatography to obtain the target product, γ-amino acid. The specific results are as follows:

[0043]

[0044] Note: All results above are separation results. Coarse NMR was used to determine the dr value of the product.

[0045] The experimental results above demonstrate that substrates with different protecting groups on nitrogen, such as alkoxycarbonyl, pivaloyl, and benzoyl, are well compatible. Azacyclic butane substrates modified with different substituents, including electron-rich, electron-poor, and electron-neutral groups, are compatible and yield the target γ-amino acid product in moderate to excellent yields. A variety of functional groups or substituents are compatible in this reaction system, including alkyl, methoxy, phenyl, fluorine, ester, phenoxy, chlorine, and naphthyl groups.

[0046] Example 2

[0047] A method for synthesizing γ-amino acid compounds based on the CN-bond carboxylation of 2-carbonyl-azacyclic butane is described below:

[0048] After drying a 10 mL Schlenk reaction tube equipped with a stir bar under vacuum, 0.2 mmol of 2-carbonylazacyclobutane (added at this stage if the substrate is solid; otherwise, added via syringe after the addition of the reducing agent if the substrate is liquid) and 4DPAIPN (2 mol%) photocatalyst were added. The tube was then placed in a glove box, and 1 equivalent of Cs₂CO₃ was added. The tube was then sealed and removed from the glove box. The tube was purged three times under a double-row CO₂ atmosphere. After purging, 2 equivalents of DIPEA (N,N-diisopropylethylamine) and 2 mL of DMAc (ultra-dry solvent) were added under a CO₂ stream. After adding the solvent, the tube was sealed and placed 1 cm away from 30 W blue (wavelength 400–480 nm) LEDs. The tube was stirred at room temperature for 24 h. After the reaction was complete, 2 mL of 2N HCl and 2 mL of ethyl acetate were added and stirred for 2 min. The tube was then extracted five times with ethyl acetate. The organic phases were combined and evaporated to dryness using a rotary evaporator. The solid residue was separated by silica gel column chromatography to obtain the target product, γ-amino acid. For some substrates, after rotary evaporation, 2 mL of MeOH and 2 mL of Et₂O were added to dissolve them. Then, 3 equivalents of TMSCHN₂ (a 2N solution in n-hexane) were added at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 h. After the reaction was complete, the mixture was evaporated to dryness using a rotary evaporator and separated by silica gel column chromatography to obtain the target product, γ-amino acid methyl ester. Specific results are as follows:

[0049]

[0050] Note: All results above are separation results. The dr value of the product was determined by coarse NMR. [a] The reaction time was 36 h.

[0051] The experimental results above demonstrate that sterically hindered aziridine substrates with different ester and amide groups react well. A variety of functional groups or substituents are compatible in this reaction system, including alkyl, alkenyl, phenyl, methoxy, cyano, and others. Importantly, aziridine substrates derived from two natural products, menthol and terpineol, are also well compatible.

[0052] Example 3

[0053] A method for synthesizing β-amino acid compounds based on the CN-bond carboxylation of aziridine is described below:

[0054] After drying a 10 mL Schlenk reaction tube equipped with a stirrer under vacuum, add 0.2 mmol of aziridine (if it is a solid substrate, add it at this time; if it is a liquid substrate, add it via syringe after adding the reducing agent) and the photocatalyst 3DPAFIPN (2 mol%). Then place it in a glove box and add 1 equivalent of tAfter removing the tube from the glove box and sealing it with COOCs, the mixture was purged three times under a double-row CO2 atmosphere. After purging, 2 equivalents of DIPEA (N,N-diisopropylethylamine) and 2 mL of DMAc (ultra-dry solvent) were added under a CO2 stream. After adding the solvent, the tube was sealed and placed 1 cm away from 30W blue (wavelength 400–480 nm) LEDs. The mixture was stirred at room temperature for 6 hours. After the reaction was complete, 2 mL of 2N HCl and 2 mL of ethyl acetate were added, and the mixture was stirred for 2 minutes. The mixture was then extracted five times with ethyl acetate. The organic phases were combined and evaporated to dryness using a rotary evaporator. The solid residue was separated by silica gel column chromatography to obtain the target product, β-amino acid. Specific results are as follows:

[0055]

[0056] Note: All results above are separation results. Coarse NMR was used to determine the dr value of the product.

[0057] The experimental results above demonstrate that aziridine substrates modified with different substituents, including electron-rich, electron-poor, and electron-neutral groups, are compatible and can yield the target β-amino acid product in moderate to excellent yields. A variety of functional groups or substituents are compatible in this reaction system, including alkyl, chlorine, fluorine, ester, and methoxy groups.

[0058] Example 4

[0059] A method for synthesizing δ- or ε-amino acid compounds based on CN-bond carboxylation of pyrrolidine or piperidine, the specific process of which is as follows:

[0060] After drying a 10 mL Schlenk reaction tube equipped with a stir bar under vacuum, 0.2 mmol of pyrrolidine or piperidine (if the substrate is solid, add it at this time; if the substrate is liquid, add it via syringe after adding the reducing agent) and photocatalyst 4DPAIPN (5 mol%) were added. The tube was then placed in a glove box, 1 equivalent of Cs2CO3 was added, the tube was sealed, and the tube was removed from the glove box. The tube was then purged three times under a double-row CO2 atmosphere. After purging, 2 equivalents of DIPEA (N,N-diisopropylethylamine) and 2 mL of NMP (ultra-dry solvent) were added under a CO2 stream. After adding the solvent, the tube was sealed and placed 1 cm away from 30 W blue (wavelength 400–480 nm) LEDs. The tube was stirred at room temperature for 24 h. After the reaction was completed, 2 mL of 2N HCl and 2 mL of ethyl acetate were added, and the mixture was stirred for 2 min. The mixture was then extracted five times with ethyl acetate. The organic phases were combined and evaporated to dryness using a rotary evaporator. The solid residue was separated by silica gel column chromatography to obtain the target product δ- or ε-amino acid. The specific results are as follows:

[0061]

[0062] Note: All the above results are separation results.

[0063] The experimental results above indicate that pyrrolidine or piperidine substrates substituted with an ester group or phenyl group at the 2-position react well. A variety of functional groups or substituents are compatible in this reaction system, including fluorine, alkenyl, ether, and phenyl groups. Importantly, citronellol-derived piperidine substrates are also well compatible.

[0064] Example 5

[0065] A method for synthesizing γ-amino alcohols based on the reaction of azacyclic butanes and alkyl aldehydes, the specific process of which is as follows:

[0066] After drying a 10 mL Schlenk reaction tube equipped with a stirrer under vacuum, add 0.2 mmol of azacyclobutane (if it is a solid substrate, add it at this stage; if it is a liquid substrate, add it via syringe after adding the reducing agent) and the photocatalyst 3DPAFIPN (2 mol%). Then place the tube in a glove box and add 1 equivalent of... t After the reaction was completed, the tube was sealed and removed from the glove box. The tube was then subjected to three purging cycles under a double-row N2 atmosphere. After purging, 2 equivalents of an alkyl aldehyde, 2 equivalents of DIPEA (N,N-diisopropylethylamine), and 2 mL of DMAc (ultra-dry solvent) were added under an N2 atmosphere. After adding the solvent, the tube was sealed and placed 1 cm away from 30W blue LEDs (wavelength 400–480 nm). The mixture was stirred at room temperature for 36 h. After the reaction was complete, 2 mL of 2N HCl and 2 mL of ethyl acetate were added, and the mixture was stirred for 2 min. The mixture was then extracted five times with ethyl acetate. The organic phases were combined and evaporated to dryness using a rotary evaporator. The solid residue was separated by silica gel column chromatography to obtain the target product, γ-amino alcohol. Specific results are as follows:

[0067]

[0068] Note: All results above are separation results. The dr value of the product was determined by coarse NMR. [a] Paraformaldehyde was used as the electrophilic coupling reagent; [b] 4DPAIPN was used instead of 3DPAFIPN.

[0069] The experimental results above demonstrate that sterically hindered alkyl aldehyde substrates and substituted azacyclobutane substrates react well. A variety of functional groups or substituents are compatible in this reaction system, including alkyl, ether, phenyl, alkenyl, methoxy, phenoxy, naphthyl, and others. Importantly, readily available and inexpensive paraformaldehyde can also be used as a substitute for formaldehyde to successfully yield the corresponding γ-amino alcohol products.

[0070] Example 6

[0071] This study used 2-phenylazacyclobutane-1-carboxylic acid tert-butanol ester as a template substrate and investigated the effect of changing reaction conditions on the reaction yield. The specific process is as follows:

[0072]

[0073] Note: The yields mentioned above are crude NMR yields, and the yields in parentheses are separation yields.

[0074] The experimental results above show that the separation yield of the corresponding amino acid under the reaction conditions of this invention is as high as 88%. A series of control experiments show that light, photocatalyst, reducing agent, alkali and CO2 are all crucial. If any one of them is missing, the yield will drop significantly, or even the target product may not be obtained.

[0075] The product obtained by this invention was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The NMR and MS data were consistent with the obtained product. Specific characterization data are as follows:

[0076] 4-(tert-Butoxycarbonyl)amino)-2-phenylbutyric acid (2a)

[0077] 2H),2.13–2.02(m,1H),1.81–1.70(m,1H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.5,155.6,139.5,128.5,127.8,127.0,77.5,48.2,38.1,33.1,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 15 H 20 NO4]-:278.1398,found:278.1393.

[0078] 4-(ethoxycarbonyl)amino-2-phenylbutyric acid (2b)

[0079] 1H),6.02(s,0.3H),4.76(s,0.7H),4.16–4.02(m,2H),3.63(t,J=7.6Hz,1H),3.22 –3.06(m,7.1Hz,2H),2.39–2.24(m,1H),2.05–1.90(m,1H),1.21(t,J=7.1Hz,3H). 13C NMR(101MHz,Chloroform-d)δ178.5,156.9,138.1,128.9,128.1,127.8,61.1,49.0,39.2,33.3,14.7.HRMS(ESI-)[MH] - Calculated m / z for [C 13 H 16 NO4] - :250.1085,found:250.1083.

[0080] 2-Phenylacetylaminobutyric acid (2c)

[0081]

[0082] 1 H NMR(400MHz,Chloroform-d)δ7.36–7.22(m,5H),5.86(s,1H),3.59(t,J=7.3H z,1H),3.34–3.17(m,2H),2.35–2.25(m,1H),2.03–1.93(m,1H),1.11(s,9H). 13 C NMR(101MHz,Chloroform-d)δ179.2,177.8,138.4,129.0,128.1,127.7,49.7,38.7,38.4,32.9,27.5.HRMS(ESI-)[MH] - Calculated m / z for [C 15 H 20 NO3] - :262.1449,found:262.1445.

[0083] 4-Benzoylamino-2-phenylbutyric acid (2d)

[0084] 7.83(d,J=7.5Hz,2H),7.56–7.42(m,3H),7.38–7.23(m,5H),3.63(t,J=7.4Hz,1H ),3.28–3.13(m,2H),2.26(dq,J=14.3,7.3Hz,1H),1.92(dq,J=14.2,7.3Hz,1H). 13C NMR(101MHz,DMSO-d6)δ174.6,166.3,139.6,134.6,131.0,128.5,128.2,127.8,127.2,127.0,48.5,37.6,32.7.HRMS(ESI-)[MH] - Calculated m / z for [C 17 H 16 NO3] - :282.1136,found:282.1131.

[0085] 4-((tert-Butoxycarbonyl)amino)-2-(4-(tert-Butyl)phenyl)butyric acid (2e)

[0086] 2H),2.36–2.20(m,1H),2.03–1.84(m,1H),1.41(s,9H),1.29(s,9H). 13 C NMR(101MHz,Chloroform-d)δ178.9,156.1,150.5,135.1,127.7,125.8,79.5,48.7,38.9,34.6,33.3,31.4,28.5.HRMS(ESI-)[MH] - Calculated m / z for [C 19 H 28 NO4] - :334.2024,found:334.2025.

[0087] 4-((tert-Butoxycarbonyl)amino)-2-(4-methoxyphenyl)butyric acid (2f)

[0088] 2.82(q,J=6.8Hz,2H), 2.03(dq,J=14.3,7.3Hz,1H), 1.72(dq,J=14.8,7.3Hz,1H), 1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.8,158.2,155.6,131.4,128.8,113.9,77.5,55.0,47.3,38.1,33.1,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 22 NO5] - :308.1503,found:308.1505.

[0089] 2-([1,1'-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)butyric acid (2g)

[0090] 1.81(dq,J=14.3,7.3Hz,1H),1.38(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.5,155.6,139.9,138.9,138.7,128.9,128.4,127.4,126.8,126.6,77.5,47.9,38.1,33.0,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 21 H 24 NO4] - :354.1711,found:354.1717.

[0091] 4-((tert-Butoxycarbonyl)amino)-2-(4-fluorophenyl)butyric acid (2h)

[0092] 2.83(q,J=6.7Hz,2H), 2.06(dq,J=14.4,7.2Hz,1H), 1.74(dq,J=14.3,7.3Hz,1H), 1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.5,161.2(d,J=242.7Hz),155.6,135.6(d,J=3.1 Hz), 129.8 (d, J = 8.1Hz), 115.2 (d, J = 21.1Hz), 77.5, 47.4, 38.0, 33.1, 28.2. 19 F NMR(376MHz,DMSO-d6)δ115.94.HRMS(ESI-)[MH] - Calculated m / z for [C 15 H 19 FNO4] - :296.1304,found:296.1300.

[0093] 4-((tert-Butoxycarbonyl)amino)-2-(4-(methoxycarbonyl)phenyl)butyric acid (2i)

[0094] 1H), 2.85 (q, J=6.8Hz, 2H), 2.11 (dq, J=14.3, 7.2Hz, 1H), 1.78 (dq, J=14.2, 7.2Hz, 1H), 1.35 (s, 9H). 13 C NMR(101MHz,DMSO-d6)δ174.0,166.1,155.6,145.0,129.4,128.4,128.3,77.6,52.1,48.3,38.0,32.9,28.2.HRMS(ESI+)[M+Na] + Calculated m / z for [C 17 H 23 [NNaO6] + :360.1418,found:360.1415.

[0095] 4-((tert-Butoxycarbonyl)amino)-2-(3-Methoxyphenyl)butyric acid (2j)

[0096] (m,4H),3.74(s,3H),3.51(t,J=7.5Hz,1H),2.84(q,J=6.7Hz,2H),2.05(dq,J=14.3,7.3Hz,1H),1.74(dq,J=14.7,7.2Hz,1H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.4,159.3,155.6,141.0,129.5,120.0,113.8,112.2,77.5,55.0,48.2,38.1,33.0,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 22 NO5] - :308.1503,found:308.1503.

[0097] 4-((tert-Butoxycarbonyl)amino)-2-(3-phenoxyphenyl)butyric acid (2k)

[0098] =7.9Hz,1H),7.17–7.12(m,1H),7.07–6.99(m,3H),6.95(t,J=2.1Hz,1H),6.90–6.80(m,2H),3.56(t,J=7 .5Hz,1H),2.86(q,J=6.8Hz,2H),2.04(dq,J=14.3,7.2Hz,1H),1.74(dq,J=14.3,7.2Hz,1H),1.36(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.3,156.7,156.5,155.6,141.8,130.1,130.0,123 .5,122.9,118.7,118.0,116.9,77.5,48.2,38.1,33.1,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 21 H 24 NO5] - :370.1660,found:370.1660.

[0099] 4-Benzoylamino-2-(3-chlorophenyl)butyric acid (2l)

[0100] 1H),7.88–7.77(m,2H),7.57–7.42(m,3H),7.41–7.27(m,4H),3.69(t,J=7.5Hz,1 H),3.25–3.15(m,2H),2.26(dq,J=14.1,7.2Hz,1H),1.94(dq,J=14.3,7.3Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ174.1,166.3,141.9,134.5,133.1,131.1,130.4,128.2,127.9,127.2,127.0,126.7,48.1,37.4,32.5.HRMS(ESI-)[MH] - Calculated m / z for [C 17 H 15 ClNO3] - :316.0746,found:316.0747.4-((tert-butoxycarbonyl)amino)-2-(o-tolyl)butyric acid (2m)

[0101] 1H),3.78(t,J=7.3Hz,1H),2.96–2.80(m,2H),2.31(s,3H),2.09(dq,J=14.0,7.0Hz,1H),1.71(dq,J=13.9,7.0Hz,1H),1.37(s,9H). 13 C NMR(101MHz,DMSO)δ174.7,155.6,138.2,135.8,130.3,126.7,126.5,126.2,77.5,43.8,38.2,32.5,28.3,19.2.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 22 NO4] - :292.1554,found:292.1554.

[0102] 4-((tert-Butoxycarbonyl)amino)-2-(naphthyl-2-yl)butyric acid (2n)

[0103] 1.7Hz,1H),7.54–7.42(m,3H),6.90(t,J=5.6Hz,1H),3.74(t,J=7.5Hz,1H),2.94–2 .83(m,2H),2.19(dq,J=14.3,7.3Hz,1H),1.88(dq,J=14.4,7.3Hz,1H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ174.5,155.6,137.0,133.0,132.1,128.1,127.6,127 .5,126.5,126.2,126.1,125.8,77.5,48.4,38.2,32.9,28.3.HRMS(ESI-)[MH] - Calculated m / z for [C 19 H 22 NO4] - :328.1554,found:328.1558.

[0104] 2-(((tert-Butoxycarbonyl)amino)methyl)-2,3-dihydro-1H-indene-1-carboxylic acid (2o)

[0105]

[0106] 1¹H NMR (400MHz, DMSO-d6, mixture of two diastereomers) δ 7.32–7.08 (m, 4H), 7.00 (t, J = 5.9 Hz 0.8H), 6.86 (t, J = 5.6 Hz, 0.2H), 3.94 (d, J = 7.8 Hz, 0.2H), 3.74 (d, J = 5.9 Hz, 0.8H), 3.22 (dt, J = 12.9, 5.5 Hz, 0.2H), 3.08–2.73 (m, 4H), 2.63 (dd, J = 16.0, 6.2 Hz, 0.8H), 1.39 (s, 2.2H), 1.39 (s, 6.8H). 13 C NMR (101 MHz, DMSO-d6, mixture of two diastereomers) δ 174.3, 173.4, 155.9, 155.7, 143.4, 142.6, 141.4, 140.5, 127.32, 127.25, 126.4, 126.2, 124.8, 124.72, 124.69, 124.6, 77.6, 53.2, 52.0, 43.3, 42.6, 41.0, 35.5, 35.2, 28.3. HRMS (ESI-) [MH] - Calculated m / z for [C 16 H 20 NO4] - :290.1398,found:290.1398.

[0107] 4-((tert-Butoxycarbonyl)amino)-2-methyl-2-phenylbutyric acid (2p)

[0108] 7.27–7.19(m,1H),6.75(t,J=5.5Hz,1H),2.91–2.73(m,2H),2.01(tt,J=9.4,6.5Hz,2H),1.47(s,3H),1.36(s,9H). 13 C NMR(101MHz,DMSO-d6)δ176.8,155.5,143.6,128.3,126.5,125.8,77.5,48.3,38.4,36.6,28.3,22.7.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 22 NO4] - :292.1554,found:292.1557.

[0109] 4-((tert-Butoxycarbonyl)amino)-2-(methoxycarbonyl)butyric acid (4a)

[0110] 3.37(t,J=7.3Hz,1H),2.94(dt,J=7.7,6.3Hz,2H),1.85(q,J=7.1Hz,2H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.3,169.8,155.6,77.6,52.1,48.8,37.8,28.8,28.2.HRMS(ESI-)[MH] - Calculated m / z for [C 11 H 18 NO6] - :260.1140,found:260.1140.

[0111] 4-((tert-Butoxycarbonyl)amino)-2-((3-Phenylacetoxy)carbonyl)butyric acid (4b)

[0112] 7.16 (m, 3H), 6.87 (t, J=5.7Hz, 1H), 4.06 (td, J=6.4, 3.6Hz, 2H), 3.39 (t, J=7.3Hz, 1 H), 2.97(qd,J=6.9,2.6Hz,2H),2.68–2.58(m,2H),1.92–1.82(m,4H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.4,169.3,155.6,141.1,128.4,125.9,77.6,63.9,48.9,37.8,31.2,29.8,28.8,28.2.HRMS(ESI-)[MH] - Calculated m / z for [C 19 H 26 NO6] - :364.1766,found:364.1765.Notes:One aromatic signal is missing in the 13 C NMR spectrum, mostly likely due to overlap with another peak.

[0113] 4-((tert-Butoxycarbonyl)amino)-2-(((4-phenylbut-2-yl)oxy)carbonyl)butyric acid (4c)

[0114] 7.30–7.23(m,2H),7.22–7.13(m,3H),6.91–6.84(m,1H),4.87–4.76(m,1H),3.39–3.34(m,1H),3.04–2 .89(m,2H),2.69–2.52(m,2H),1.93–1.72(m,4H),1.37(s,4.6H),1.37(s,4.4H),1.19(t,J=6.2Hz,3H). 13 C NMR (101 MHz, DMSO-d6, mixture of two diastereomers) δ 170.5, 170.3, 168.82, 168.80, 155.60, 155.57, 141.4, 141.3, 128.30, 128.29, 128.28, 125.8, 77.6, 70.7, 70.6, 49.1, 37.8, 37.1, 36.9, 30.8, 30.7, 28.8, 28.7, 28.2, 19.6, 19.5. HRMS (ESI-) [MH] - Calculated m / z for [C 20 H 28 NO6] - :378.1922,found:378.1916.

[0115] 4-((tert-Butoxycarbonyl)amino)-2-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)carbonyl)butyric acid (4d)

[0116] 6.81(m,1H),4.59(tt,J=10.9,3.9Hz,1H),3.33(q,J=7.1Hz,2H),3.00–2.86(m,2H),1.94–1.78(m,4 H),1.70–1.58(m,2H),1.51–1.30(m,11H),1.10–0.91(m,2H),0.90–0.78(m,6H),0.74–0.66(m,3H). 13 C10 NMR (101 MHz, DMSO-d6, mixture of two diastereomers) δ 170.3, 170.2, 168.8, 155.6, 155.5, 77.5, 74.3, 74.2, 49.0, 46.4, 46.3, 37.8, 33.7, 30.81, 30.79, 28.73, 28.69, 28.2, 25.5, 25.4, 22.84, 22.82, 21.9, 20.5, 16.1, 16.0. HRMS (ESI-) [MH] -Calculated m / z for [C 20 H 34 NO6] - :384.2392,found:384.2392.

[0117] 4-((tert-Butoxycarbonyl)amino)-2-(((2-(4-methylcyclohexane-3-en-1-yl)propyl-2-yl)oxy)carbonyl)butyric acid (4e)

[0118] 6.84(t,J=5.7Hz,1H),5.37–5.31(m,1H),3.26–3.19(m,1H),2.99–2.87(m,2H),2.03–1. 86(m,4H),1.84–1.72(m,4H),1.65–1.56(m,3H),1.43–1.33(m,15H),1.23–1.14(m,1H). 13 CNMR (101MHz, DMSO-d6, mixture of two diastereomers) δ 170.5, 168.2, 155.6, 133.2, 120.3, 85.18, 85.15, 77.5, 50.0, 49.9, 42.5, 42.4, 37.8, 30.4, 28.7, 28.2, 25.7, 25.6, 23.20, 23.17, 23.1, 23.0, 22.9, 22.8, 22.7. HRMS (ESI-) [MH] - Calculated m / z for [C 20 H 32 NO6] - :382.2235,found:382.2235.2-(tert-Butoxycarbonyl)-4-((tert-Butoxycarbonyl)amino)butyric acid (4f)

[0119] 7.3Hz,1H),3.00–2.89(m,2H),1.80(q,J=7.1Hz,2H),1.40(s,9H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.6,168.5,155.6,80.8,77.6,49.9,37.8,28.8,28.3,27.6.HRMS(ESI+)[M+Na] + Calculated m / z for [C 14 H 25 [NNaO6] + :326.1574,found:326.1574.

[0120] 4-((tert-Butoxycarbonyl)amino)-2-(methyl(phenyl)carbamoyl)butyric acid (4g)

[0121] 2H),7.39(t,J=7.2Hz,1H),7.31(d,J=7.5Hz,2H),6.66(t,J=5.7Hz,1H),3.23(t,J=7. 0Hz, 1H), 3.18 (s, 3H), 2.81 (q, J=6.5Hz, 2H), 1.86–1.68 (m, J=6.6Hz, 2H), 1.36 (s, 9H). 13 C NMR(101MHz,DMSO-d6)δ171.0,168.2,155.5,143.3,129.7,127.9,127.6,77.5,45.9,37.9,37.2,29.3,28.3.HRMS(ESI+)[M+Na] + Calculated m / z for [C 17 H 24 [N2NaO5] + :359.1577,found:359.1573.4-((tert-butoxycarbonyl)amino)-2-((4-methoxyphenyl)(methyl)carbamoyl)butyric acid (4h)

[0122] 7.1Hz,1H),3.13(s,3H),2.85–2.75(m,2H),1.82–1.71(m,2H),1.35(s,9H). 13 C NMR(101MHz,DMSO-d6)δ171.0,168.5,158.5,155.5,135.9,128.7,114.8,77.5,55.3,45.8,37.9,37.3,29.2,28.2.HRMS(ESI+)[M+Na] + Calculated m / z for [C 18 H 26 [N2NaO6] + :389.1683,found:389.1686.

[0123] 4-((tert-Butoxycarbonyl)amino)-2-(isopropyl(phenyl)carbamoyl)butyric acid (4i)

[0124] 8.4,5.9Hz,1H),2.87–2.75(m,2H),1.77(ddt,J=29.9,13.4,6.6Hz,2H),1.37(s,9H),0.98(dd,J=6.8,1.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ171.1,167.5,155.5,137.7,130.5,129.2,128.5,77.5,47.0,45.7,37.9,29.2,28.3,20.7,20.6.HRMS(ESI+)[M+H] + Calculated m / z for [C 19 H 29 N2O5] + :365.2071,found:365.2070.

[0125] 4-((tert-Butoxycarbonyl)amino)-2-((2-Cyanoethyl)(phenyl)carbamoyl)butyric acid (4j)

[0126] (dt,J=13.3,6.3Hz,1H),3.17(t,J=7.1Hz,1H),2.83(q,J=6.6Hz,2H),2.71(t,J=6.6Hz,2H),1.88–1.70(m,2H),1.35(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.6,168.7,155.5,140.9,129.8,128.5,118.8,77.5,46.3,44.7,37.8,29.3,28.2,28.0,15.9.HRMS(ESI+)[M+Na] + Calculated m / z for [C 19 H 25 [N3NaO5] + :398.1686,found:398.1686.

[0127] Methyl 4-((tert-butoxycarbonyl)amino)-2-(dimethylcarbamoyl)butyrate (4k)

[0128] 3.25–3.12(m,2H),3.08(s,3H),2.99(s,3H),2.21–2.06(m,2H),1.43(s,9H). 13C NMR(101MHz,Chloroform-d)δ170.4,168.6,156.1,79.4,52.6,46.5,39.0,37.7,36.2,29.5,28.5.HRMS(ESI+)[M+Na] + Calculated m / z for [C 13 H 24 [N2NaO5] + :311.1577,found:311.1574.

[0129] Methyl 4-((tert-butoxycarbonyl)amino)-2-(pyrrolidine-1-carbonyl)butyrate (4l)

[0130] 3.49–3.39(m,2H),3.29(t,J=6.9Hz,2H),2.98–2.84(m,2H),1.91–1.75(m,6H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.1,166.2,155.7,77.6,52.0,47.1,46.3,45.7,37.7,28.8,28.2,25.5,23.9.HRMS(ESI+)[M+Na] + Calculated m / z for [C 15 H 26 [N2NaO5] + :337.1734,found:337.1733.

[0131] 3-((tert-Butoxycarbonyl)amino)-2-phenylpropionic acid (6a)

[0132] J=5.6Hz,1H),3.76(t,J=7.6Hz,1H),3.50–3.41(m,1H),3.21(dd,J=13.4,6.7Hz,1H),1.33(s,9H). 13 C NMR(101MHz,DMSO-d6)δ173.6,155.6,137.5,128.5,128.1,127.2,77.8,50.8,43.0,28.2.HRMS(ESI+)[M+Na] + Calculated m / z for [C 14 H 19 [NNaO4] + :288.1206,found:288.1205.

[0133] 3-Benzoylamino-2-phenylpropionic acid (6b)

[0134] 7.82–7.70(m,2H),7.53–7.47(m,1H),7.46–7.39(m,2H),7.38–7.23(m,5H),4.00(t, J=7.6Hz,1H),3.78(ddd,J=13.2,8.0,5.2Hz,1H),3.59(ddd,J=13.1,7.2,5.9Hz,1H). 13 CNMR(101MHz,DMSO-d6)δ173.6,166.5,137.5,134.4,131.2,128.6,128.2,128.0,127.3,127.1,50.3,42.4.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 14 NO3] - :268.0979,found:268.0978.

[0135] 3-Benzoylamino-2-(4-(tert-butyl)phenyl)propionic acid (6c)

[0136] (m,2H),7.54–7.47(m,1H),7.47–7.40(m,2H),7.40–7.34(m,2H),7.28–7.20(m,2H),3.97( dd,J=8.2,6.8Hz,1H),3.77(ddd,J=13.4,8.2,5.3Hz,1H),3.58–3.49(m,1H),1.26(s,9H). 13 C NMR(101MHz,DMSO-d6)δ173.8,166.5,149.6,134.6,134.4,131.2,128.2,127.6,127.2,125.4,49.8,42.5,34.2,31.1.HRMS(ESI-)[MH] - Calculated m / z for [C 20 H 22 NO3] - :324.1605,found:324.1601.

[0137] 3-Benzoylamino-2-(p-Tolyl)propionic acid (6d)

[0138] 7.80–7.72(m,2H),7.56–7.47(m,1H),7.43(dd,J=8.2,6.6Hz,2H),7.20(d,J=8.1Hz,2H),7.14(d,J=8.0Hz,2H ),3.95(t,J=7.6Hz,1H),3.75(ddd,J=13.2,8.0,5.2Hz,1H),3.55(ddd,J=13.1,7.2,5.8Hz,1H),2.27(s,3H). 13 C NMR(101MHz,DMSO-d6)δ173.7,166.4,136.4,134.5,134.3,131.2,129.1,128.2,127.8,127.1,49.9,42.4,20.6.HRMS(ESI-)[MH] - Calculated m / z for [C 17 H 16 NO3] - :282.1136,found:282.1136.

[0139] 3-Benzoylamino-2-(4-chlorophenyl)propionic acid (6e)

[0140] (m,2H),7.54–7.47(m,1H),7.47–7.38(m,4H),7.38–7.31(m,2H),4.01(t,J=7.6 Hz,1H),3.78(ddd,J=12.7,7.4,5.1Hz,1H),3.60(ddd,J=13.5,7.8,6.0Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ173.3,166.5,136.6,134.3,132.0,131.2,130.0,128.5,128.3,127.2,49.7,42.2.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 13 ClNO3] - :302.0589,found:302.0584.

[0141] 3-Benzoylamino-2-(4-fluorophenyl)propionic acid (6f)

[0142] 2H),7.54–7.47(m,1H),7.43(dd,J=8.2,6.6Hz,2H),7.39–7.31(m,2H),7.22–7.12(m,2H),4 .00(t,J=7.6Hz,1H),3.77(ddd,J=13.0,7.7,5.1Hz,1H),3.59(ddd,J=13.3,7.6,6.0Hz,1H). 13 C NMR (101MHz, DMSO-d6) δ173.5, 166.5, 161.4 (d, J = 243.1Hz), 134.3, 133.7 (d, J = 3 .2Hz), 131.2, 130.0 (d, J = 8.2Hz), 128.3, 127.1, 115.3 (d, J = 21.3Hz), 49.5, 42.3. 19 F NMR(376MHz,DMSO-d6)δ115.48.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 13 FNO3] - :286.0885,found:286.0889.

[0143] 3-Benzoylamino-2-(4-(methoxycarbonyl)phenyl)propionic acid (6g)

[0144] =7.8Hz,2H),7.74(d,J=7.5Hz,2H),7.50–7.35(m,5H),4.10(t,J=7.6Hz,1H),3.90–3.75(m,4H),3.70–3.58(m,1H). 13 C NMR(101MHz,DMSO-d6)δ173.0,166.5,166.0,143.0,134.3,131.2,129.4,128.6,128.3,127.1,52.1,50.4,42.1.HRMS(ESI+)[M+Na] + calculated m / z for [C 18 H 17 [NNaO5] + :350.0999,found:350.0996.

[0145] 3-Benzoylamino-2-(3-chlorophenyl)propionic acid (6h)

[0146] 7.81–7.69(m,2H),7.53–7.47(m,1H),7.47–7.40(m,2H),7.40–7.31(m,3H),7.31–7.24(m,1H) ,4.02(t,J=7.5Hz,1H), 3.79(ddd,J=12.7,7.3,5.0Hz,1H), 3.62(ddd,J=13.4,7.8,6.0Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ173.1,166.5,139.9,134.3,133.0,131.2,130.4,128.3,127.9,127.3,127.1,127.0,49.9,42.1.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 13 ClNO3] - :302.0589,found:302.0589.

[0147] 3-Benzoylamino-2-(3-methoxyphenyl)propionic acid (6i)

[0148] (m,2H),7.53–7.48(m,1H),7.47–7.39(m,2H),7.29–7.22(m,1H),6.91–6.83(m,3 H),3.97(t,J=7.5Hz,1H),3.80–3.70(m,4H),3.57(ddd,J=13.1,7.3,5.8Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ173.5,166.5,159.3,139.0,134.4,131.2,129.6,128.2,127.1,120.3,113.7,112.6,55.0,50.2,42.3.HRMS(ESI-)[MH] - Calculated m / z for [C 17 H 16 NO4] - :298.1085,found:298.1083.

[0149] 3-Benzoylamino-2-(o-Tolyl)propionic acid (6j)

[0150] 2H),7.54–7.47(m,1H),7.47–7.40(m,2H),7.30–7.25(m,1H),7.22–7.12(m,3H),4.28(dd,J=8 .5, 6.4Hz, 1H), 3.77 (ddd, J=13.6, 8.5, 5.5Hz, 1H), 3.50 (dt, J=13.1, 6.0Hz, 1H), 2.37 (s, 3H). 13 C NMR(101MHz,DMSO-d6)δ174.4,167.1,136.9,136.6,134.8,131.6,130.9,128.7,127.6,127.5,127.1,126.7,46.5,42.6,19.7.HRMS(ESI-)[MH] - calculated m / z for [C 17 H 16 NO3] - :282.1136,found:282.1135.

[0151] 3-Benzoylamino-2-(2-chlorophenyl)propionic acid (6kJ)

[0152] 7.83–7.69(m,2H),7.59–7.39(m,5H),7.38–7.26(m,2H),4.48(t,J=7.4Hz,1H),3.91(dt,J=12.8,6.1Hz,1H),3.61(dt,J=13.6,6.7Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ172.8,166.5,135.5,134.4,133.6,131.1,129.6,129.5,128.9,128.2,127.4,127.1,47.0,41.3.HRMS(ESI-)[MH] - Calculated m / z for [C 16 H 13 ClNO3] - :302.0589,found:302.0593.

[0153] 3-Benzoylamino-2-methyl-2-phenylpropionic acid (6l)

[0154] 2H),7.54–7.47(m,1H),7.47–7.30(m,6H),7.28–7.22(m,1H),3.84(qd,J=13.4,6.2Hz,2H),1.55(s,3H). 13 C NMR(101MHz,DMSO-d6)δ176.3,167.0,142.0,134.7,131.1,128.3,128.2,127.3,126.8,126.2,51.0,46.4,21.3.HRMS(ESI-)[MH] - Calculated m / z for [C 17 H 16 NO3] - :282.1136,found:282.1132.

[0155] 2-Benzoylamino-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (6m)

[0156]

[0157] 1 ¹H NMR (400 MHz, DMSO-d⁶, mixture of two diastereomers) δ 12.50 (s, 1H), 8.51 (t, J = 7.5 Hz, 1H), 7.90–7.79 (m, 2H), 7.57–7.43 (m, 3H), 7.23–7.07 (m, 4H), 4.54 (qd, J = 10.3, 8.8, 6.0 Hz, 0.7H), 4.30–4.23 (m, 0.3H),4.23–4.18(m,0.3H),3.96(d,J=9.2Hz,0.7H),2.97–2.90(m,0.6H),2.90–2.83(m,1 .4H),2.49–2.41(m,0.3H),2.09–1.98(m,0.7H),1.89–1.82(m,0.3H),1.82–1.67(m,0.7H). 13C NMR (101 MHz, DMSO-d6, mixture of two diastereomers) δ 174.6, 173.5, 166.4, 165.9, 136.0, 135.8, 134.7, 134.6, 133.3, 133.2, 131.2, 131.1, 129.4, 129.0, 128.9, 128.24, 128.16, 127.9, 127.4, 127.3, 126.9, 126.7, 126.1, 125.7, 51.0, 48.4, 47.8, 47.6, 28.0, 27.92, 27.88, 23.5. HRMS (ESI-) [MH] - Calculated m / z for [C 18 H 16 NO3] - :294.1136,found:294.1132.

[0158] 5-(tert-Butoxycarbonyl)amino)-2-phenylpentanoic acid (8a)

[0159] 1H),1.68–1.56(m,1H),1.35(s,11H). 13 C NMR(101MHz,CD3OD)δ177.6,158.5,140.9,129.6,129.0,128.2,79.9,52.5,40.9,31.7,29.0,28.8.HRMS(ESI+)[M+Na] + Calculated m / z for [C 16 H 23 [NNaO4] + :316.1519,found:316.1516.

[0160] 5-((tert-Butoxycarbonyl)amino)-2-(methoxycarbonyl)valeric acid (8b)

[0161] Hz, 2H), 1.40–1.31 (m, 11H). 13 C NMR(101MHz,DMSO-d6)δ170.4,170.0,155.6,77.4,52.0,50.9,28.3,27.2,25.7.HRMS(ESI+)[M+Na] + Calculated m / z for [C 12 H 21 [NNaO6] + :298.1261,found:298.1260.

[0162] 5-((tert-Butoxycarbonyl)amino)-2-((2-Fluoroethoxy)carbonyl)valeric acid (8c)

[0163] (dd,J=4.7,3.4Hz,1H),4.54(dd,J=4.7,3.4Hz,1H),4.36(td,J=3.6,2.0Hz,1H),4.28(td,J=3.6,2.1 Hz,1H),3.41(t,J=7.5Hz,1H),2.91(q,J=6.5Hz,2H),1.73(tt,J=9.8,4.3Hz,2H),1.41–1.32(m,11H). 13 C NMR (101MHz, DMSO-d6) δ170.3, 169.5, 155.6, 81.5 (d, J = 166.5Hz), 77.5, 64.0 (d, J = 19.0Hz)., 50.9, 28.3, 27.2, 25.7. 19 F NMR(376MHz,DMSO-d6)δ223.22.HRMS(ESI+)[M+Na] + Calculated m / z for [C 13 H 22 FNNaO6] + :330.1323,found:330.1319.

[0164] 4-(((tert-Butoxycarbonyl)amino)methyl)-2-(methoxycarbonyl)pent-4-enoic acid (8d)

[0165] 1.7Hz,1H),4.75(s,1H),3.63(s,4H),3.51(d,J=6.1Hz,2H),2.44(d,J=7.7Hz,2H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ170.0,169.6,155.6,143.7,110.9,77.7,52.1,49.8,44.1,32.2,28.2.HRMS(ESI+)[M+Na] + Calculated m / z for [C 13 H 21 [NNaO6] + :310.1261,found:310.1260.

[0166] 5-((tert-Butoxycarbonyl)amino)-2-((((S)-3,7-dimethyloct-6-en-1-yl)oxy)carbonyl)pentanoic acid (8e)

[0167] 3.3Hz,2H),3.32(t,J=7.5Hz,1H),2.90(q,J=6.6Hz,2H),2.03–1.86(m,2H),1.75–1.65(m,2H),1.6 4(d,J=1.4Hz,3H),1.62–1.45(m,5H),1.42–1.24(m,13H),1.18–1.08(m,1H),0.86(d,J=6.6Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ170.4,169.5,155.6,130.6,124.5,77.4,62.9,51.1,36.4 ,34.8,28.81,28.78,28.3,27.2,25.7,25.5,24.9,19.1,17.5.HRMS(ESI+)[M+Na] + Calculated m / z for [C 21 H 37 [NNaO6] + :422.2513,found:422.2516.

[0168] 6-((tert-Butoxycarbonyl)amino)-2-(methoxycarbonyl)hexanoic acid (8f)

[0169] 3H),3.32(t,J=7.5Hz,1H),2.88(q,J=6.6Hz,2H),1.72(q,J=7.6Hz,2H),1.39–1.32(m,11H),1.25–1.19(m,2H). 13 C NMR(101MHz,DMSO-d6)δ170.4,170.0,155.6,77.4,52.0,51.3,39.6,29.2,28.3,28.2,24.1.HRMS(ESI+)[M+Na] + Calculated m / z for [C 13 H 23 [NNaO6] + :312.1418,found:312.1414.

[0170] 6-((tert-Butoxycarbonyl)amino)-2-((2-Methoxyethoxy)carbonyl)hexanoic acid (8g)

[0171] 4.18(td,J=4.3,2.8Hz,2H),3.51(dd,J=5.1,4.2Hz,2H),3.31(t,J=7.5Hz,1H),3.25(s ,3H),2.88(q,J=6.6Hz,2H),1.80–1.63(m,2H),1.42–1.31(m,11H),1.27–1.17(m,2H). 13 CNMR(101MHz,DMSO-d6)δ170.4,169.6,155.6,77.4,69.6,63.8,58.1,51.4,39.6,29.2,28.3,28.2,24.0.HRMS(ESI+)[M+Na] + Calculated m / z for [C 15 H 27 [NNaO7] + :356.1680,found:356.1679.6-((tert-butyloxycarbonyl)amino)-2-((hex-5-en-1-yloxy)carbonyl)hexanoic acid (8h)

[0172] 5.78(ddt,J=16.9,10.1,6.6Hz,1H),5.06–4.92(m,2H),4.07(td,J=6.5,3.4Hz,2H),3.29(t,J=7.5Hz,1H),2.88( q,J=6.6Hz,2H),2.06–1.99(m,2H),1.76–1.66(m,2H),1.60–1.52(m,2H),1.41–1.31(m,13H),1.25–1.20(m,2H). 13 C NMR(101MHz,DMSO-d6)δ.170.5,169.5,155.6,138.4,115.0,77.3,64.4,51.4,39.6,32.7,29.2,28.3,28.1,27.5,24.5,24.1.HRMS(ESI+)[M+Na] + Calculated m / z for [C 18 H 31 [NNaO6] + :380.2044,found:380.2046.

[0173] 6-((tert-Butoxycarbonyl)amino)-2-((3-Phenylacetoxy)carbonyl)hexanoic acid (8i)

[0174] Hz,2H),7.19(d,J=7.4Hz,3H),6.77(t,J=5.8Hz,1H),4.11–4.00(m,2H),3.32(t,J=7.5Hz,1H),2.89(q,J=6.6Hz,2H), 2.62(dd,J=8.6,6.7Hz,2H),1.87(dq,J=8.9,6.5Hz,2H),1.73(q,J=7.7Hz,2H),1.41–1.32(m,11H),1.27–1.19(m,2H). 13 C NMR(101MHz,DMSO-d6)δ170.5,169.5,155.6,141.1,128.4,128.3,125.9,77 .3,63.8,51.4,39.6,31.2,29.8,29.3,28.3,28.1,24.1.HRMS(ESI+)[M+Na] + Calculated m / z for [C 21 H 31 [NNaO6] + :416.2044,found:416.2043.

[0175] 6-((tert-Butoxycarbonyl)amino)-2-(((tetrahydro-2H-pyran-4-yl)methoxy)carbonyl)hexanoic acid (8j)

[0176] 3.93(qd,J=10.8,6.4Hz,2H),3.83(ddd,J=11.6,4.5,1.9Hz,2H),3.32–3.24(m,3H),2.87(q,J=6.6Hz ,2H),1.90–1.78(m,1H),1.76–1.66(m,2H),1.56–1.49(m,2H),1.41–1.31(m,11H),1.26–1.20(m,4H). 13 C NMR(101MHz,DMSO-d6)δ170.5,169.5,155.6,77.4,68.6,66.5,51.5,39.6,34.0,29.2,28.9,28.3,28.1,24.1.HRMS(ESI+)[M+Na] + Calculated m / z for [C 18 H 31 [NNaO7] + :396.1993,found:396.1990.

[0177] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxy-6-phenylhexyl)aminocarbonate (10a)

[0178] (m,1H),1.98–1.80(m,2H),1.76–1.53(m,2H),1.41(s,9H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.2, 156.1, 142.14, 142.06, 140.93, 140.88, 140.86, 140.0, 139.7, 139.5, 129.4, 128.9, 128.8, 128.6, 128.54, 128.52, 1 28.47,127.48,127.47,127.34,127.31,127.11,127.09,126.0,125.9,79.3,75.1, 74.2,49.9,49.3,39.2,37.1,36.8,32.6,32.4,32.3,32.0,28.5.HRMS(ESI+)[M+Na] + Calculated m / z for [C 29 H 35 [NNaO3] + :468.2509,found:468.2506.

[0179] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxyhexyl)aminocarbonate (6b)

[0180] –7.19(m,1H),4.51(s,1H),3.75–3.60(m,1H),3.15–2.90(m,2H),2.77–2.62(m,1H),2.25–2.12(m,1H),2.04–1.83(m,2H ),1.59–1.45(m,1H),1.42(s,4.4H),1.42(s,4.6H),1.36–1.27(m,1H),0.97(t,J=7.4Hz,1.4H),0.92(t,J=7.4Hz,1.6H). 13C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.2, 156.1, 141.3, 140.93, 140.92, 139.9, 139.7, 139.6, 129.4, 128.9, 128.8, 127.43, 127.38, 127.30, 127.27, 127.10, 127.08, 79.3, 76.1, 49.5, 48.7, 39.5, 32.6, 31.8, 28.5, 28.01, 27.98, 10.3, 10.2. HRMS (ESI+) [M+Na] + Calculated m / z for [C 23 H 31 [NNaO3] + :392.2196,found:392.2198.

[0181] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxyheptyl)aminocarbonate (10c)

[0182] (d,J=8.0Hz,1H),4.52(s,1H),3.82–3.69(m,1H),3.14–2.90(m,2H),2.72–2.61(m,1H),2.23–2.10(m,1H),2.04–1.81(m,2 H),1.55–1.44(m,2H),1.42(s,4.5H),1.42(s,4.5H),1.37–1.28(m,2H),0.91(t,J=6.9Hz,1.5H),0.85(t,J=6.8Hz,1.5H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.14, 156.05, 141.3, 140.9, 139.84, 139.75, 139.6, 129.4, 128.9, 128.8, 127.42, 127.37, 127.30, 127.27, 127.09, 127.07, 79.2, 75.4, 74.5, 49.9, 49.2, 39.4, 39.2, 37.4, 37.3, 32.6, 31.7, 28.5, 19.2, 19.1, 14.2, 14.1. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 33 [NNaO3] + :406.2353,found:406.2355.

[0183] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxyoctyl)aminocarbonate (10d)

[0184] 7.23(d,J=7.9Hz,1H),4.52(s,1H),3.82–3.66(m,1H),3.13–2.90(m,2H),2.72–2.61(m,1H),2.23–2.10(m,1H ),2.08–1.82(m,2H),1.50–1.37(m,11H),1.33–1.23(m,4H),0.89(t,J=6.8Hz,1.5H),0.84(t,J=6.8Hz,1.5H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.1, 156.0, 141.3, 140.9, 140.93, 139.91, 139.7, 139.6, 129.4, 128.9, 128.8, 127.43, 127.39, 127.31, 127.28, 127.10, 127.08, 79.2, 75.7, 74.8, 49.8, 49.2, 39.3, 39.2, 34.9, 34.8, 32.6, 31.6, 28.5, 28.14, 28.13, 22.8, 22.7, 14.20, 14.16. HRMS (ESI+) [M+Na] + Calculated m / z for [C 25 H 35 [NNaO3] + :420.2509,found:420.2509.

[0185] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxynonyl)aminocarbonate (10e)

[0186] 2.89(m,2H),2.72–2.61(m,1H),2.22–2.11(m,1H),2.03–1.84(m,2H),1.49–1.37(m,11H),1.31–1.19(m,6H),0.90–0.82(m,3H). 13C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.1, 156.0, 141.3, 140.92, 140.90, 139.8, 139.7, 139.6, 129.4, 128.9, 128.8, 127.40, 127.35, 127.29, 127.26, 127.08, 127.07, 79.2, 75.7, 74.8, 49.9, 49.2, 39.3, 39.2, 35.2, 35.1, 32.6, 32.0, 31.8, 31.7, 28.5, 25.7, 25.6, 22.8, 22.7, 14.2, 14.1. HRMS (ESI+) [M+Na] + Calculated m / z for [C 26 H 37 [NNaO3] + :434.2666,found:434.2663.

[0187] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxy-6-methylheptyl)carbamate (10f)

[0188] 3.15–2.90(m,2H),2.68–2.58(m,1H),2.22–2.09(m,1H),2.04–1.75(m,3H),1.46–1.39( m,9H),1.26–1.08(m,2H),0.90(dd,J=6.7,3.2Hz,2.9H),0.85(dd,J=13.0,6.6Hz,3.1H). 13 CNMR (101MHz, Chloroform-d, mixture of two diastereomers) δ 156.2, 156.1, 141.2, 140.9, 139.8, 139.7, 139.6, 129.5, 128.9, 128.8, 127.41, 127.36, 127.30, 127.27, 127.08, 127.07, 79.3, 73.6, 72.7, 50.3, 49.8, 44.5, 44.4, 39.3, 32.7, 31.5, 28.5, 24.72, 24.68, 23.9, 23.8, 21.9, 21.6. HRMS (ESI+) [M+Na] + Calculated m / z for [C 25 H 35 [NNaO3] + :420.2509,found:420.2507.

[0189] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxy-6,6-dimethylheptyl)aminocarbonate (10g)

[0190] 1.74–1.62(m,1H),1.49–1.35(m,10H),1.25–1.11(m,1H),0.93(s,4.4H),0.88(s,4.6H). 13 CNMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.1, 141.3, 140.9, 139.8, 139.6, 129.4, 129.0, 128.9, 127.38, 127.37, 127.30, 127.28, 127.08, 127.07, 79.2, 73.2, 72.5, 51.1, 50.9, 49.2, 49.0, 39.3, 32.6, 31.1, 30.4, 30.3, 30.25, 30.16, 28.5. HRMS (ESI+) [M+Na] + Calculated m / z for [C 25 H 35 [NNaO3] + :434.2666,found:434.2664.

[0191] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxy-5-methylhexyl)aminocarbonate (10h)

[0192] 7.22(d,J=7.9Hz,1H),4.63–4.43(m,1H),3.59–3.45(m,1H),3.16–2.89(m,2H),2.86–2.70(m,1H),2.2 7–2.16(m,1H),2.04–1.80(m,2H),1.65–1.52(m,1H),1.42(s,4.4H),1.42(s,4.6H),1.01–0.84(m,6H). 13C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.2, 156.1, 141.8, 140.9, 140.2, 139.8, 139.6, 129.4, 128.9, 128.6, 127.5, 127.4, 127.29, 127.26, 127.09, 127.07, 80.4, 79.7, 79.3, 46.9, 46.3, 39.4, 39.2, 33.1, 32.3, 30.8, 30.0, 28.5, 20.4, 20.1, 16.9, 15.3. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 33 [NNaO3] + :406.2353,found:406.2358.

[0193] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-cyclohexyl-4-hydroxybutyl)aminocarbonate (10i)

[0194] –2.78(m,3H),2.22–2.09(m,1H),2.02–1.53(m,8H),1.42(s,4.4H),1.42(s,4.6H),1.25–1.05(m,5H). 13 C NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.2, 156.0, 141.8, 140.9, 140.2, 139.7, 139.5, 129.5, 128.9, 128.7, 127.5, 127.4, 127.28, 127.26, 127.08, 127.06, 80.1, 79.3, 79.0, 45.9, 45.5, 40.5, 40.1, 39.5, 39.1, 33.1, 31.3, 30.4, 30.3, 28.5, 27.3, 26.55, 26.53, 26.40, 26.35, 26.09, 26.05. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 33 [NNaO3] + :446.2666,found:446.2666.

[0195] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)butyl)aminocarbonate (10j)

[0196] 3.58–3.43(m,1H),3.33–3.18(m,2H),3.14–2.76(m,3H),2.21–2.10(m,1H),2.04–1.84(m,2H),1.71–1.57(m,2H),1.53–1.35(m,12H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers, s) δ 156.2, 156.1, 141.5, 140.8, 140.7, 139.8, 139.7, 139.6, 129.5, 128.9, 128.6, 127.5, 127.34, 127.31, 127.02, 127.00, 79.2, 79.1, 78.1, 67.91, 67.89, 67.8, 67.6, 45.5, 45.0, 39.2, 39.1, 38.1, 37.7, 33.4, 31.2, 29.9, 29.8, 28.5, 28.2, 26.9. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 33 [NNaO3] + :448.2458,found:448.2457.

[0197] tert-Butoxycarbonyl (3-([1,1'-biphenyl]-4-yl)-4-hydroxytetrahept-13-en-1-yl)carbamate (10k)

[0198] (m,2H),4.57–4.45(m,1H),3.81–3.67(m,1H),3.14–2.89(m,2H),2.71–2.61(m,1 H),2.22–2.11(m,1H),2.07–1.82(m,4H),1.52–1.39(m,11H),1.37–1.22(m,12H). 13C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.14, 156.05, 141.3, 140.91, 140.90, 139.9, 139.7, 139.6, 139.33, 139.32, 129.4, 128.9, 128.8, 127.43, 127.38, 127.30, 127.27, 127.09, 127.07, 114.2,79.2,75.7,74.8,49.9,49.2,39.4,39.3,35.3,35.1,33.92,33.91,32.6,31.7,29.75,29 .68,29.6,29.63,29.60,29.5,29.23,29.21,29.04,29.02,28.5,26.0,25.9.HRMS(ESI+)[M+Na] + Calculated m / z for [C 31 H 45 [NNaO3] + :502.3292,found:502.3293.

[0199] tert-Butyl(3-([1,1'-biphenyl]-4-yl)-4-hydroxybutyl)carbamate (10l)

[0200] 12.2, 6.5Hz, 1H), 1.99 (dq, J=13.5, 6.7Hz, 1H), 1.86–1.76 (m 1H), 1.43 (s, 9H). 13 C NMR(101MHz,Chloroform-d)δ156.1,140.9,140.8,140.1,128.9,128.5,127.7,127.4,127.1,79.4,67.5,45.9,39.0,32.6,28.5.HRMS(ESI+)[M+Na] + Calculated m / z for [C 31 H 45 [NNaO3] + :364.1883,found:364.1883.

[0201] tert-butyl(4-hydroxy-3-phenylhexyl)carbamate (10m)

[0202] 7.27(m,2H),7.26–7.19(m,2H),7.18–7.12(m,1H),4.47(s,1H),3.71–3.58(m,1H),3.09–2.83(m,2H),2.69–2.55(m,1H),2. 22–2.10(m,1H),2.04–1.75(m,2H),1.58–1.34(m,10H),1.30–1.20(m,1H),0.96(t,J=7.4Hz,1.5H),0.90(t,J=7.4Hz,1.5H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.1, 156.0, 142.2, 140.6, 129.0, 128.78, 128.75, 128.4, 127.1, 126.8, 79.3, 76.1, 49.9, 49.1, 39.2, 32.6, 31.9, 28.5, 27.97, 27.96, 10.3, 10.2. HRMS (ESI+) [M+Na] + Calculated m / z for [C 17 H 27 [NNaO3] + :316.1883,found:316.1886. tert-butyl(4-hydroxy-3-(3-methoxyphenyl)heptyl)carbamate (10n)

[0203] 7.19(m,1H),6.84–6.69(m,3H),4.50(s,1H),3.80(s,1.5H),3.80(s,1.5H),3.71–3.56(m,1H),3.09–2.86(m,2H),2.67–2.54(m,1H),2. 20–2.09(m,1H),1.93–1.74(m,2H),1.42(s,4.5H),1.41(s,4.5H),1.33–1.20(m,2H),0.96(t,J=7.4Hz,1.5H),0.90(t,J=7.4Hz,1.5H). 13C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 159.872, 159.865, 156.1, 156.0, 144.0, 142.4, 129.74, 129.72, 121.3, 120.7, 115.0, 114.5, 112.0, 111.6, 79.2, 76.1, 55.3, 50.0, 49.2, 39.3, 39.2, 32.5, 31.9, 28.5, 28.0, 27.9, 10.23, 10.21. HRMS (ESI+) [M+Na] + Calculated m / z for [C 18 H 29 [NNaO4] + :346.1989,found:346.1988.

[0204] tert-butyl(4-hydroxy-3-(3-phenoxyphenyl)heptyl)carbamate (10o)

[0205] 7.02–6.83(m,5H),4.51(s,1H),3.78–3.62(m,1H),3.13–2.87(m,2H),2.65–2.53(m,1H),2.20–2.08(m,1H), 1.98–1.76(m,2H),1.49–1.33(m,11H),1.30–1.21(m,2H),0.89(t,J=7.0Hz,1.5H),0.84(t,J=6.8Hz,1.5H). 13 C NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 157.5, 157.4, 157.34, 157.28, 156.1, 156.0, 144.5, 142.9, 130.0, 129.92, 129.87, 123.9, 123.4, 123.34, 123.31, 119.6, 118.90, 118.88, 118.8, 117.3, 117.1, 79.3, 75.3, 74.4, 50.2, 49.4, 39.3, 37.39, 37.37, 32.5, 31.8, 28.5, 19.1, 19.0, 14.2, 14.1. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 33 [NNaO4] + :422.2302,found:422.2299.

[0206] tert-butyl(4-hydroxy-3-(2-naphthyl)heptyl)carbamate (10p)

[0207] (m,1H),3.87–3.74(m,1H),3.08–2.91(m,2H),2.83–2.73(m,1H),2.29–2.18(m,1H),2.08–1.89(m,2H),1.50–1 .42(m,2H),1.40(s,4.4H),1.39(s,4.6H),1.30–1.23(m,2H),0.89(t,J=6.9Hz,1.4H),0.80(t,J=6.8Hz,1.6H). 13 C10 NMR (101 MHz, Chloroform-d, mixture of two diastereomers) δ 156.1, 156.0, 139.8, 138.3, 133.6, 133.5, 132.7, 132.6, 128.5, 128.4, 127.9, 127.8, 127.7, 127.2, 126.9, 126.4, 126.21, 126.18, 125.7, 125.6, 79.2, 75.4, 74.5, 50.5, 49.8, 39.4, 39.3, 37.45, 37.42, 32.6, 31.8, 28.5, 19.13, 19.08, 14.2, 14.0. HRMS (ESI+) [M+Na] + Calculated m / z for [C 22 H 31 [NNaO3] + :380.2196,found:380.2196.

[0208] Although specific embodiments of the present invention have been described in detail with reference to examples, they should not be construed as limiting the scope of protection of this patent. Various modifications and variations that can be made by those skilled in the art without inventive effort within the scope described in the claims are still within the scope of protection of this patent.

Claims

1. A method for synthesizing amino acids and amino alcohols, characterized in that, Includes the following steps: A cyclic amine compound, a photocatalyst, and a base were mixed, and then a reducing agent and an organic solvent were added under a CO2 atmosphere to obtain a reaction solution. The reaction solution was stirred under light and room temperature conditions, and then the reaction product was acidified and purified to obtain an amino acid compound. Alternatively, a cyclic amine compound, a photocatalyst, and a base can be mixed, and then a reducing agent, an aldehyde / ketone compound, and a solvent can be added under an inert atmosphere to obtain a reaction solution. The reaction solution is stirred under light and room temperature conditions, and then the reaction product is acidified and purified to obtain an amino alcohol compound. The photocatalyst is a DA-type photocatalyst or an Ir-type photocatalyst; the reducing agent is an organic amine compound; the wavelength of the visible light used for illumination is 300~700 nm; The general structural formula of the cyclic amine compound is shown in Formula (I), and the general structural formula of the aldehyde / ketone compound is shown in Formula (II): The synthesis route is as follows: The cyclic amine compound of formula (I) is selected from any of the following: ； The aldehyde / ketone compound of formula (II) is selected from any of the following: 。 2. The method for synthesizing amino acids and amino alcohols as described in claim 1, characterized in that, The molar ratio of the cyclic amine compound, photocatalyst, base, and reducing agent is 1:0.0001~0.5:0.1~10:1~10; the molar ratio of the cyclic amine compound, photocatalyst, base, reducing agent, and aldehyde / ketone compound is 1:0.0001~0.5:0.1~10:1~10:0.1~10.

3. The method for synthesizing amino acids and amino alcohols as described in claim 1, characterized in that, The base is a tert-butanol salt, carbonate, bicarbonate, fluoride salt, phosphate, hydrogen phosphate, carboxylate, or organic base.

4. The method for synthesizing amino acids and amino alcohols as described in claim 3, characterized in that, The tert-butanol salt is KO t Bu, NaO t Bu、LiO t Bu or Ca(O t Bu)2; the carbonate is Cs2CO3, K2CO3, Na2CO3 or Li2CO3; the bicarbonate is CsHCO3, KHCO3 or NaHCO3; the fluoride is CsF, KF, NaF or LiF; the phosphate is K3PO4, Na3PO4 or Li3PO4; the carboxylate is CsOAc, KOAc, NaOAc, CsOPiv, NaOPiv or KOPiv; the organic base is DBU, TBD, DABCO, TMG, DBN, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3 or NET3.

5. The method for synthesizing amino acids and amino alcohols as described in claim 1, characterized in that, The organic amine compounds are DBU, TBD, DABCO, TMG, DBN, and DIPEA. i Pr2NEt, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3, or NET3.

Images