98 results about "Chemoselectivity" patented technology

The present disclosure provides a method for the chemoselective modification of a target molecule. The subject methods comprise contacting a target molecule comprising a thiol moiety with a biomolecule comprising a reactive moiety, wherein the reactive moiety is produced by reacting a biomolecule comprising a phenol moiety or catechol with an enzyme capable of oxidizing the phenol moiety or the catechol moiety. The contacting is performed under conditions sufficient to conjugate the target molecule to the biomolecule, thereby producing a modified target molecule. The present disclosure provides compositions comprising a subject target molecule comprising a thiol moiety and a biomolecule comprising a phenol moiety or a catechol moiety. The present disclosure provides kits for performing the subject methods. The disclosure also provides modified target molecules and methods of using the same.

The 18F-labeling of unprotected peptides and sugars via thioarylation using a Au(III)-[˜F]fluoroaryl complex is reported. The chemoselective method generates 18F-labeled S-aryl bioconjugates in an aqueous environment in 15 min with high radiochemical yields and displays excellent functional group tolerance. This approach utilizes an air and moisture stable, robust organometallic Au(III) complex and highlights the versatility of designer organometallic reagents as efficient agents for rapid radiolabeling.

The invention discloses a compound containing a bicyclic hemiketal structure and a preparation method thereof, alkynyl allyl carbonate is used as a raw material, in the presence of a nucleophilic catalyst, alkynyl allyl carbonate reacts with a benzoylacetonitrile derivative, ABB'multi-component reaction is carried out through a continuous [5 + 1] / addition / cyclization reaction sequence, and the compound containing the bicyclic hemiketal structure is obtained. Bicyclic hemiketal derivatives commonly seen in natural product structures are obtained with good to excellent diastereoselectivity. The method has the advantages of good diastereoselectivity products, excellent chemical selectivity, greenness, mild reaction conditions, convenience in operation, few byproducts and the like, the synthesis steps are good in economy, and four chemical bonds and three continuous chiral centers are simultaneously constructed through one-step operation. Meanwhile, the compound with the bicyclic hemiketal structure has important application value in multiple fields of medicinal chemistry, natural product chemistry, traditional Chinese medicine chemistry and the like, and an efficient preparation means and a series of candidate compounds are provided for development of functionality or biological activity of related compounds with the bicyclic hemiketal / hemiacetal structure.

The present invention provides targeting polyplexes comprised of (i) nucleic acids, in particular nucleic acids encoding pharmaceutically active peptides or proteins, and (ii) targeting conjugates comprising LPEI and PEG fragments that are connected by discrete linkages formed through defined, chemoselective reactions. Thus, the LPEI fragment is bonded in a linear end- to-end fashion to a single PEG fragment. The linear conjugates are further conjugated to a targeting fragment to enable selective interaction with a particular cell type. The polyplexes selectively deliver the nucleic acids to the targeted cells resulting in high expression and efficient protein translation as well as secretion of the encoded pharmaceutically active proteins.

The invention discloses a method for preparing benzyl borate compounds through chromium catalysis, and belongs to the technical field of organic synthesis. According to the method, aryl carboxylic ester is taken as a raw material, pinacolborane is taken as a boron source and a hydrogen source, metal chromium salt is taken as a catalyst, a specific ligand and elemental magnesium are added, and reaction is performed in a tetrahydrofuran solvent, so that the deoxidation boronization reaction of the aryl carboxylic ester is realized. Benzyl monoborate or benzyl subunit diborate can be selectively prepared through ligand regulation and control. The method has the advantages of mild reaction conditions, cheap catalyst, wide raw material source, simple operation and good chemical selectivity.

The application discloses a method for synthesizing a chiral secondary phosphine oxide with a conjugated dienyl phosphorus center through desymmetrization. The method is that a primary phosphine oxide reacts with an alkyne to obtain the chiral secondary phosphine oxide with the conjugated dienyl phosphorus center under the joint catalysis of zero-valent nickel and a ligand and the action of an additive. The method realizes the preparation of the chiral secondary phosphine oxide with the conjugated dienyl phosphorus center with high enantioselectivity and specific chemical selectivity through the joint catalysis of the zero-valent nickel and the ligand.

The preparation of high-value-added aromatic carboxylic acids via CO2 carboxylation coupling through activation of the benzyl C-H bond in alcohols / amines is a green and sustainable pathway to achieve CO2 resource utilization and contribute to carbon neutrality. However, this field currently faces challenges such as poor catalyst selectivity, low CO2 activation efficiency, and a narrow substrate applicability range, making it difficult to meet practical application needs. To address this issue, this patent discovers that in a heterogeneous electrocatalytic system, cuprous selenide (V2), rich in selenium vacancies, can be used... Se -Cu 2‑x Using Se as the core catalyst, it can not only efficiently promote the synergistic activation of benzyl C-H bonds and CO2 carboxylation, significantly improving the overall catalytic activity of the reaction, but also achieve precise chemoselective carboxylation control for different types of substrates. Specifically, this V Se -Cu 2‑x Se electrocatalysts can efficiently and selectively activate the benzyl C-H bond in alcohols and subsequently induce CO2 carboxylation, exhibiting excellent chemoselectivity in the conversion of benzyl alcohol to mandelic acid and its derivatives. Simultaneously, they also demonstrate excellent catalytic performance for amines, selectively catalyzing the carboxylation of amine substrates such as benzylamine with CO2 to directionally generate phenylglycine and aromatic amine-derived carboxylates. Crucially, in addition to typical benzyl alcohol and benzylamine, the substrate applicability of this catalytic system can be extended to various alcohols and amine derivatives, realizing the carboxylation transformation from simple model substrates to diverse functional molecules, providing a new approach for the large-scale preparation of high-value-added aromatic carboxylates.

The application provides a preparation method of 3-aryl / alkyl-beta-naphthyl ether compounds, and the preparation method comprises the following steps: reacting trimethyl orthoformate with 1,3-diaromatic propyl ketone compounds or 1-aryl-3-alkyl ketone compounds to obtain 3-aryl-beta-naphthyl ether compounds or 3-alkyl-beta-naphthyl ether compounds. The reaction condition of the application is mild, trimethyl orthoformate is cheap and easy to obtain, can be used as a methylation reagent and a carbon source for extending a carbon chain at the same time, the range of reaction substrates is wide, and the functional group tolerance is good; the reaction is efficient, the selectivity is high, the post-treatment is simple, the operation is simple, and the application is suitable for large-scale industrial production; the complex substrate prepared in advance in the traditional reaction is avoided, the metal catalyst necessary for the traditional reaction is not needed, the binaftyl alcohol precursor compounds can be prepared with high chemical selectivity, and a more simple and efficient route is provided for the olefin hydroformylation / hydroformyl esterification reaction for synthesizing bidentate ligands.

The invention discloses an alpha-fluoro alpha, beta-unsaturated amide derivative as well as a synthesis method and application thereof. The preparation method comprises the following steps: by taking amyl-1, 1, 2-trifluoro-1, 4-diene which is simple and convenient to prepare and a cheap and abundant amine compound as raw materials, an allyl palladium chloride dimer as a transition metal catalyst, 1, 4-bis (diphenylphosphine) butane as a ligand and 2, 5-di-tert-butylbenzoquinone as an oxidant, reacting in an organic solvent at a proper temperature under a nitrogen condition, thereby obtaining the 1, 1, 2-trifluoro-1, 4-diene compound. The alpha-fluoro alpha, beta-unsaturated amide derivative is obtained with good yield, and the structural formula of the derivative is shown in the specification. The synthesis method disclosed by the invention has the characteristics of simplicity and convenience in operation, mild conditions, greenness, economy, wide substrate compatibility, high chemical selectivity and high regioselectivity, and solves the technical problem that the synthesis conditions of the alpha-fluoro-alpha, beta-unsaturated amide derivative are complicated and harsh. Meanwhile, the alpha-fluoro drug molecules can be efficiently and highly selectively obtained, and the method has a wide application prospect.

The invention discloses a synthesis method of a novel fluorine-containing allyl tertiary nitro alkane compound, which comprises the following steps: by taking a gem-difluorocyclopropane derivative and sec-nitro alkane as raw materials, carrying out ring opening on gem-difluorocyclopropane under the catalysis of transition metal to generate a fluorine allyl-metal complex; and then reacting with sec-nitro alkane to obtain the straight-chain fluorine-containing allyl tert-nitro alkane compound. The method has obvious advantages in the aspects of synthesis conditions and practicability, has the advantages of simple synthesis steps, simplicity and convenience in operation, cheap and easily available raw materials, good compatibility to functional groups, high chemical selectivity, high reaction efficiency and the like, and is more in line with green and sustainable chemistry concepts; and reference and reliable technical support are provided for efficient synthesis of the fluorine-containing allyl tertiary nitro alkane compound.

The application relates to a transition metal-catalyzed N-(1-arylvinyl)amide for constructing a fully substituted 5,5'-oxazole compound through a multiple cross-dehydrogenative coupling strategy. Specifically, under the condition of an inert solvent, through the joint promotion of a transition metal catalyst and a silver salt oxidant, multiple dehydrogenation 1,1-bifunctionalization of olefins is realized. The method has good regioselectivity and chemical selectivity. Notably, the application reports the first case of a transition metal-catalyzed simple construction of a fully substituted 5,5'-oxazole compound skeleton based on a multiple dehydrogenation cyclization strategy. The substrate of the conversion has a wide application range and strong functional group tolerance. The applicant also realizes the modification of drug molecules such as propyl sulfone. Further, the obtained 5,5'-oxazole molecules are subjected to fluorescence testing, and the fluorescence quantum yield reaches 83.14%, indicating that the novel skeleton has great application potential in luminescent materials.

The present disclosure provides a method for chemoselective modification of a cell surface molecule on a target cell. A subject method includes contacting a target cell comprising cell surface molecule comprising a thiol, an amine, or an imidazole with a biomolecule comprising a reactive moiety, wherein the reactive moiety is generated by reaction of a biomolecule (e.g., an antibody) comprising a phenol moiety or a catechol with an enzyme capable of oxidizing the phenol or the catechol moiety. The contacting is carried out under conditions sufficient for conjugation of the cell surface molecule to the biomolecule, thereby producing a modified cell. The present disclosure provides kits for carrying out a subject method. The present disclosure also provides modified cells and methods for using same.

The present invention relates to a novel method for preparing a benzyl α-hydroxyketone derivative by mono-α-arylating O-protected hydroxyacetone with a palladium catalyst, followed by deprotection.

The application discloses a synthetic method of introducing a trans-isopentenyl group at the C3 position of indole. The method uses indole and 2-methyl-2-butene as starting materials, and a palladate as a catalyst. Through direct oxidative dehydrogenation coupling reaction, the trans-isopentenyl group can be introduced at the C3 position of the indole with high regioselectivity and chemoselectivity. Compared with traditional methods of introducing a trans-isopentenyl group at the C3 position of indole, the method has the advantages of simple operation, low price of reagents, mild reaction conditions, no need for pre-functionalization of the substrate, no need for using ligands, and high atom utilization rate.

The invention relates to a method for preparing 2-aryl-3-difluoromethyl benzothiophene by utilizing an electrochemical reaction. Specifically, the invention provides an electrochemical anodic oxidation cathode reduction characteristic instead of a traditional chemical oxidation reducing agent, sodium difluoromethanesulfinate is used as a difluoromethyl donor, and a difluoromethyl free radical is excited through electrochemical anodic oxidation, so that the difluoromethyl free radical is synthesized. The preparation of the target molecule 2-aryl-3-difluoromethyl benzothiophene is realized through intramolecular cyclization initiated by addition of free radicals to active alkyne. The method does not need to add an additional transition metal catalyst and a super-stoichiometric redox agent, has the advantages of mild reaction conditions, high product yield, good chemical selectivity and the like, better conforms to the purpose of green and sustainable development of the current society, and has a good industrial application prospect.

The invention discloses a synthesis method of 2-aryl-5-alkyl-3-pyridylthiophene, which comprises the following steps: by taking 3-pyridylthiophene, alkyl bromide and chlorobenzene as raw materials, catalyzing by using a ruthenium catalyst, and carrying out a three-component reaction by using a one-pot method to prepare the 2-aryl-5-alkyl-3-pyridylthiophene. According to the method, selective carbon-hydrogen bond activation of C2 and C5 sites of 3-pyridyl thiophene is realized by utilizing a ruthenium catalyst, so that precise bifunctional modification is completed in a single reaction system. According to the invention, the 2-aryl-5-alkyl-3-pyridyl thiophene with a clear structure is successfully constructed, and the technical vacancy of related fields in the aspect of regioselective one-pot bifunctionalization is made up. Compared with a traditional fractional step method, the method has the advantages of simplified reaction steps, convenience in operation, good functional group compatibility, relatively high chemical selectivity, regioselectivity, atom economy and the like, is suitable for efficient construction of various heterocyclic compounds, and has a good application prospect.

The application discloses a [2.2] cyclophane coumarin fluorescent probe, a preparation method and a method for detecting chiral molecules, and the fluorescent probe comprises a fluorescent probe structure, and the fluorescent probe structure is shown as formula (I). The [2.2] cyclophane skeleton is introduced into the coumarin molecule, and the fluorescent probe can be applied to fluorescence recognition of chiral molecules. The fluorescent probe can chemoselectively and enantioselectively recognize histidine in a mixed solution of tetrahydrofuran and HEPES aqueous solution, and can quantitatively detect the concentration of histidine and the ee value of histidine. The probe is an achiral fluorescent probe, can reduce the difficulty of separation of chiral compounds, greatly reduces the synthesis cost of the fluorescent probe, and opens up a new amino acid recognition probe.

The application discloses a kind of by density functional theory reveals the calculation method of micro-mechanism and selectivity source of palladium catalysis olefin amine 1,2-diarylation reaction, belong to the intersection technical field of organic synthesis and computational chemistry. Including constructing molecular structure;The configuration optimization and calculation are carried out to molecular structure, obtain thermodynamic data;The geometric configuration of intermediate and transition state in each step is calculated, the change of gibbs free energy is obtained, the connection relationship of transition state and corresponding reactant, product is determined;According to thermodynamic data and connection relationship, reaction path diagram is drawn, and reaction mechanism is determined;According to reaction mechanism, the step of determining the selectivity of reaction region, enantioselectivity and chemical selectivity is determined, and selectivity control strategy is analyzed and output. By simulation, the key intermediate and transition state structure of each element step of reaction is determined, the reaction energy barrier of each element step is quantified, the transition state action mechanism determining the selectivity of reaction region, enantioselectivity and chemical selectivity is analyzed in depth, to provide theoretical guidance for the design of high-efficiency catalyst and the optimization of reaction condition.

The present invention generally relates to the field of metabolite analysis as it applies to compounds, formulations and methods which can be used to detect metabolites such as formaldehyde and methanol. More particularly, the present invention pertains to β-keto amide compounds which are particularly useful as superior and sufficiently chemoselective detection reagent in the detection of metabolites, notable formaldehyde and related compounds, such as methanol. The present invention also pertains to methods for detecting formaldehyde or methanol, as well as to formulations and kits comprising the β-keto amide compounds, and to the use thereof in the detecting formaldehyde or methanol.

The invention discloses a method for preparing ring-expanded amine or chain-extended amine from saturated amine, which comprises the following steps: in a glove box filled with nitrogen or inert gas, adding saturated amine, a first solvent, alkyne and a first catalyst into a first reaction container, heating and stirring, and carrying out ring expansion reaction to obtain ring-expanded amine or chain-extended amine; when two ends of alkyne are respectively connected with CO2Me and H, the method further comprises the following steps: adding the obtained ring-extended amine or chain-extended amine, a second solvent and alkali into a second reaction container, and heating and stirring to fully hydrolyze the ring-extended amine or chain-extended amine to obtain corresponding carboxylic acid; and at room temperature, adding the obtained carboxylic acid, a third solvent and a second catalyst into a third reaction container, then putting the third reaction container into a high-pressure kettle, filling hydrogen, and carrying out a stirring reaction to obtain completely reduced amine. The method does not use a transition metal catalyst, is good in chemical selectivity, wide in substrate application range and wide in functional group compatibility, and can be used for later functional group modification of drug molecules.

The invention relates to the field of chemical synthesis, and discloses a method for constructing a full-alkyl quaternary carbon stereocenter through stereospecific conversion of chiral tertiary alcohol. The method successfully solves the industrial problem that the peralkyl quaternary carbon center is difficult to construct with high stereoselectivity due to huge steric hindrance and lack of electron difference, the process shows excellent stereospecificity and chemical selectivity, the ee value of the product is as high as 98%, the dr value is superior to 20: 1, and meanwhile, the excellent yield of 90% or above is kept; besides, according to the scheme, the substrate is wide in universality and can be compatible with various chemical small molecule substrates of different structures, the used reagents such as triethyl aluminum and KHMDS are cheap and easy to obtain, operation is easy and convenient, and a simple and efficient stereospecific conversion strategy with industrial application potential is provided for synthesis of complex drug intermediates.

The invention discloses a method for synthesizing a phthalide compound with high selectivity under a biological compatibility condition. According to the method, a thiol compound and a 2-formyl benzoate compound are taken as raw materials, coupling is efficiently and rapidly realized in a PBS buffer solution under the action of potassium carbonate, and a phthalide product is generated. The reaction has the advantages of high yield and high reaction speed, shows excellent chemical selectivity on cysteine sulfydryl, and can effectively distinguish other nucleophilic amino acids. The method disclosed by the invention is wide in substrate applicability, simple and convenient in steps, low in cost, mild and green in conditions and good in functional group compatibility, and provides an efficient, safe and practical new way for construction of a linker of an antibody-coupled drug (ADC) and modification of phthalide active molecules.

This invention discloses an indoline fused heterocyclic compound, its preparation method, and its applications, belonging to the field of pharmaceutical synthesis technology. The method includes the following steps: using quinone imine monoketal and α,β-unsaturated cycloalkenyl ether as raw materials, and employing a Brønsted acid-phosphonic acid catalyst, a Brønsted acid-catalyzed [3+2] tandem cyclization reaction is carried out to obtain the indoline fused heterocyclic compound. The method provided by this invention features readily available raw materials and mild conditions, while also exhibiting high regioselectivity, chemoselectivity, and atom economy. The product can be efficiently separated by column chromatography, providing an excellent pathway for the large-scale preparation of this type of compound. Furthermore, the indoline fused heterocyclic compound provided by this invention has a significant inhibitory effect on the growth of human cervical cancer cells (HeLa), demonstrating good antitumor biological activity, which is of great positive significance for promoting the development of antitumor drugs.

The present application relates to the theoretical and computational chemistry technical field, specifically relates to a kind of method for predicting chemical reaction using orbital coefficient vector projection.The present application obtains different site, different direction atomic vector reaction index and other activity index by the valence orbital coefficient vector projection method developed, the coefficient vector projection in the multiple possible valence orbital overlap direction in molecule is calculated, so that different site, different direction atomic vector reaction index is obtained.By comparing the atomic vector reaction index of different sites, the activity of site can be predicted, i.e.the possibility of atom participating in chemical reaction at the site.By calculating the atomic vector reaction index of different sites, directional charge density and corresponding reaction energy barrier, the possibility of multiple potential reaction sites in molecule to occur chemical reaction can be quantitatively and directionally predicted, which will have potential application value for solving the problems such as activity prediction and chemical selectivity control of reaction in precise synthesis.

The application discloses a method for synthesizing dibenzyl-alpha,alpha-diphenylamine compounds, and belongs to the technical field of organic synthesis. The method uses aromatic dialdehyde, 2-cyclohexenone and benzylamine as raw materials, and carries out a heating reaction in an organic solvent in the presence of titanium tetrachloride. After the reaction is completed, an N,N'-dibenzyl-substituted dibenzyl-alpha,alpha-diphenylamine intermediate is separated and purified. The intermediate is subjected to hydrogenation and debenzylization by using Pd-C / H2, and after separation and purification, the dibenzyl-alpha,alpha-diphenylamine compound is obtained. The preparation process is mild and simple, and the problems of low chemical selectivity and low regioselectivity in traditional synthesis are avoided. In addition, the aryl compatibility of the aromatic dialdehyde is good, and the atomic economy is high, thereby providing raw material support for new drug screening and monomer synthesis of organic functional materials.

This invention provides a method for preparing isoxa sulfoxides and sulfones. The method first prepares an isoxa sulfoxide intermediate, then oxidizes the intermediate to isoxa sulfones. This method not only improves the conversion rate of isoxa sulfoxides but also avoids the Pummerer rearrangement and decomposition side reactions and related subsequent side reactions, solving the problems in the preparation of isoxa sulfones using existing technologies. Compared with existing technologies, this method for preparing isoxa sulfoxides has advantages such as good chemoselectivity, high yield, less waste, low cost, and high safety; the molar amount of oxidant used in the preparation of isoxa sulfones is also reduced. The method for preparing isoxa sulfoxides and sulfones provided by this invention is suitable for industrial production.

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.