50 results about "Synthon" patented technology

The invention relates to an inverse synthesis route planning method and system based on a multi-modal large model, and belongs to the technical field of chemical synthesis and artificial intelligence crossing. The method comprises the following specific steps: firstly, extracting three-dimensional molecular structure characteristics of a target product through a molecular encoder, and aligning the three-dimensional molecular structure characteristics with text modals of molecules; secondly, reasoning a possible reaction mechanism and a reaction type, and reducing an inverse synthesis search space; secondly, splitting a target product into reasonable synthesis subunits through structured marking and vocabulary expansion, data-driven atomic assignment learning and reaction center recognition and activity prediction; finally, SMILES representations and reaction paths of the reactants are generated. According to the method, the accuracy and interpretability of inverse synthesis path planning can be improved, and a new technical means is provided for automation and intellectualization in the fields of new drug development, material design and the like.

An apparatus for improving a model for use in optimizing a multistep molecular reaction is provided. The apparatus includes an automated synthesis platform, and a computing system comprising one or more processors and memory addressable by the one or more processors. A plurality of instances of the molecular reaction is performed using synthons and normalized conditions. For each respective instance, at least a subset of the synthons is transformed using the molecular reaction, generating compounds. For each respective instance, a respective conversion value is obtained. A subset of instances is selected based on at least a threshold conversion value for the respective conversion value of each respective instance. The subset of instances is used to adjust one or more parameters in a plurality of parameters of the model, obtaining an updated plurality of parameters for the model. Using, subsequent to obtaining the updated plurality of parameters, the model to search for and identify an updated plurality of normalized conditions for the molecular reaction that collectively have an improved conversion value for the molecular reaction relative to the original plurality of normalized conditions.

Systems and methods for querying a combinatorial synthesis library comprising a plurality of compounds and representing a plurality of reaction types, where each reaction type maps to a plurality of reactants, and each reactant maps to a plurality of synthons, accepts a query in the form of a single graph into a molecular encoder model, thereby obtaining a query vector. The query vector is inputted into a reaction query generator model thereby obtaining a first reaction type and a first plurality of reactants. A synthon is determined for each reactant by inputting the reactant into a synthon query generator model. A set of synthons is therefore determined, each corresponding to a reactant in the first plurality of reactants. A molecular structure in the combinatorial synthesis library is identified that includes the set of synthons arranged in accordance with a synthesis rule associated with the first reaction type.

Embodiments of the present disclosure relate to modeling DEL data using factorized molecular representations (e.g., hierarchical single and double synthon building blocks), which leverages the hierarchical structure inherent to these molecules. Using factorized molecular representations, machine learning models are trained to learn the underlying binding affinity of compounds to targets and one or more covariates (e.g., loading / repeat noise). This results in machine learning models producing improved predictions in the form of higher enrichment scores that have good correlation with compound-target binding affinity.

Carbon is one of the most common elements in bioactive organic compounds. Theoretically, nearly all carbon-based organic functional groups can be labeled with 11C if an appropriate 11C-synthon is developed and utilized. Although there are various reports on developing PET agents based on alkyl [11C]nitriles, efficient and facile cyanation of arenes with radioisotope-containing reagents, particularly electron-rich arenes, still requires further improvements. The organic photoredox-catalyzed cyanation method reported herein introduces a [11C]nitrile quickly with high radiochemical conversion (RCC) in a metal-free manner, which can also be further diversified to other functional groups such as [11C]carboxylic acids, [11C]amides, and [11C]alkyl amines.

The invention is entitled "Formation of Synthons". The present disclosure provides, among other things, a composition comprising: a 5'-3' exonuclease; a strand displacement polymerase; and optionally, a single-stranded DNA binding protein and / or a ligase. Also described are polynucleotide assembly methods for forming synthons and kits for performing the methods.

The invention discloses a tetrazine probe synthon and a preparation method and application thereof.The preparation method comprises the following steps that under the inert atmosphere, diethyl cyanomethylphosphonate, 3-hydroxypropionitrile, 3-mercaptopropionic acid and hydrazine hydrate are mixed and then react at the room temperature, a sodium nitrite solution is added after the reaction is finished, then acid is continuously added till the reaction system reaches acidity, and a tetrazine probe synthon product is obtained; continuously reacting to obtain an intermediate; and dissolving the intermediate in a solvent in an inert atmosphere, adding triethylamine, slowly adding methanesulfonyl chloride, and reacting at room temperature to obtain the tetrazine probe synthon shown in the formula I. The invention further discloses a preparation method of the tetrazine probe synthon. The tetrazine probe synthon provided by the invention can perform series Heck reaction and HWE reaction, so that controllable combination of functional groups on two sides of a tetrazine coupling probe is realized under mild reaction conditions, and the functional groups on two sides are designed according to actual requirements to regulate and control photophysical properties of the probe. A brand new way is provided for developing a high-performance biological orthogonal fluorescent probe.

This invention discloses a fluorine-containing unsaturated hydroxyindole compound, its preparation method, and its applications. Using (E)-3-nitromethylene hydroxyindole as the key synthon, it is synthesized via S... N A series of novel hydroxyindole derivatives were designed and constructed using the V-reaction, and their antibacterial activities were explored. The method for constructing fluorinated unsaturated hydroxyindole compounds obtained by this invention is of positive significance for promoting the synthesis and widespread application research of hydroxyindole compounds.

The invention relates to a multi-component organic molecular cage compound, which has C = N, B-N and B-O bonds formed through a bonding reaction, and has a connecting structure as shown in the following formula I: # imgabs0 which is assembled by three types of synthons of tetraaldehyde calix [4] resorcinol aromatic hydrocarbon, amino-substituted phenylboronic acid and alcohol. The multi-component organic molecular cage can change the type of alcohol through simple post-exchange to realize the change of optical properties and the like of the material, so that the application of the material in different fields is realized. The multi-component organic molecular cage material is simple in preparation process, low in cost, easy and convenient to operate and high in yield, and the prepared product is high in chemical stability, large in specific surface area and good in repeatability and has very high operability and practicability.

The invention discloses a chiral phenol calix [4] aryl porous organic molecular cage material as well as a preparation method and application thereof. A chiral calix [4] arene raceme and an acyl chloride chiral auxiliary agent are used as initial raw materials to react to prepare a pair of diastereoisomers, gram-grade separation is achieved through silica gel column chromatography, then the chiral auxiliary agent is removed respectively, and the single enantiomer chiral phenol calix [4] arene compound with the ee value being 99.9% or above can be obtained. The preparation method comprises the following steps of: synthesizing tetraaldehyde chiral phenol calix [4] arene by introducing an aldehyde group unit on the tetraaldehyde chiral phenol calix [4] arene through Duff reaction, and assembling the tetraaldehyde chiral phenol calix [4] arene serving as a construction element with a polyamino organic synthesizer to prepare the chiral phenol calix [4] arene porous organic cage with a larger cavity. The preparation method of the chiral porous organic cage does not need a catalyst, the preparation process is simple, operation is easy and convenient, expansibility is good, the yield is high, and the prepared chiral molecular cage is large in cavity, large in specific surface area and good in repeatability and can be used for chiral recognition and gas adsorption.

Embodiments of the disclosure involve modeling DEL data using factorized molecular representations (e.g., hierarchical mono-synthon and di-synthon building blocks), which capitalizes on the inherent hierarchical structure of these molecules. Using the factorized molecular representations, machine learning models are trained to learn latent binding affinity of compounds for targets and one or more covariates (e.g., load / replicate noise). This leads to improved predictions by the machine learning models in the form of higher enrichment scores, which are well-correlated with compound-target binding affinity.

The present invention relates to an inverse synthesis route planning method and system based on a multimodal large model, belonging to the cross - technical field of chemical synthesis and artificial intelligence. The specific steps of this method are as follows: First, extract the three - dimensional molecular structure features of the target product through a molecular encoder and align them with the text modality of the molecule; Second, infer possible reaction mechanisms and reaction types to narrow the inverse synthesis search space; Then, split the target product into reasonable synthon units through structured tagging and vocabulary expansion, data - driven atom assignment learning, and reaction center identification and activity prediction; Finally, generate the SMILES representation of the reactants and the reaction path. The present invention can improve the accuracy and interpretability of inverse synthesis path planning, providing new technical means for the automation and intelligence in fields such as new drug development and material design.

The invention discloses a synthesis method of indoline and benzotriaza compounds, and belongs to the field of organic synthesis. According to the invention, alpha-halogenated hydrazone and 2-aminochalcone are used as reactants, a ring closing alkali is added, and a reaction is carried out in an organic solvent at 0-60 DEG C for 2-24 hours to respectively obtain indoline as shown in a formula (I) or a benzotriaza compound as shown in a formula (II). According to the present invention, the alpha-halogenated hydrazone is adopted as the one-carbon synthon to participate in the cyclization reaction, such that the indoline derivative is constructed, and the benzotriaza compound is synthesized; the method is simple to operate and high in yield, and has excellent diastereoselectivity (gt; 19: 1). In addition, the invention also expands the range of the alpha-halogenated hydrazone participating in the [3 + 4] cyclization reaction as a triatomic synthon. # imgabs0 #

The present application relates to the technical field of organic synthesis, in particular to a synthesis method of polysubstituted pyrazole compounds, which comprises adding aryl diazonium salt 0.6 mmol, enone 0.9 mmol, 0.5 ml of acid and 0.3 mmol of electrolyte into a 10 ml three-necked bottle, and then adding 6 ml of solvent to dissolve; using a carbon rod as an anode and a platinum plate as a cathode, stirring the reaction, monitoring the reaction process by using thin layer chromatography, after the reaction is completed, extracting the mixture with ethyl acetate; drying the organic layer of the mixture with anhydrous sodium sulfate, rotary evaporating the solvent under reduced pressure, purifying the residue by column chromatography, and obtaining the target product; the method uses aryl diazonium salt as a double synthetic substrate under mild electrochemical conditions, continuously generates two free radicals by electrochemical reduction of aryl diazonium salt, directly synthesizes a series of polysubstituted pyrazole compounds, directly and orderly constructs polysubstituted pyrazole compounds without transition metal or external redox agent, is environment-friendly, efficient and high in atom economy.

Synthesis of O-benzotriazole and O-imidazole synthons are described. Uses of synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the synthons and uses of azapeptides and other peptidomimetics are also described.

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.

The application provides a reaction molecule prediction method, a training method, a device and an electronic device. The method comprises: performing feature extraction on a product molecule to obtain a feature of the product molecule; based on the feature of the product molecule, using a reverse reaction prediction model to predict a conversion path between the product molecule and a plurality of reaction molecules, to obtain a target path; and synthesizing a sub-path and completing a sub-path according to the target path to obtain a plurality of reaction molecules corresponding to the product molecule. The method provided by the application can not only reduce the prediction complexity of the reaction molecules and improve the generalization performance of the reaction molecule prediction, but also improve the prediction performance of the reaction molecules. The plurality of reaction molecules corresponding to the sub-path; the basic graph comprises a plurality of atoms or edges for connecting the atoms.

The present invention discloses a strong π Electron delocalized α,β-unsaturated nitrile and preparation method thereof, which is a compound ( Z )-3-amino-2-nitroacrylonitrile. The present invention also discloses ( Z )-3-amino-2-nitroacrylonitrile, comprising: using 5-amino-4-nitro-3-azido-1 H ‑pyrazole as the starting material, 1,4‑dioxane as the solvent, thermal denitrification reaction, and then purification by silica gel column chromatography to obtain ( Z )-3-amino-2-nitroacrylonitrile. Due to its high thermal stability, π With its electron delocalization characteristics and excellent reactivity, it is a very important synthon and intermediate in organic synthesis. Its preparation method is simple, with high yield and conversion rate, and it is green and pollution-free. It has broad application prospects in biochemistry, medicinal chemistry, and material chemistry.

The invention discloses a method for synthesizing a gem-difluoroolefin compound through conversion of alkane under catalysis of acridine. The gem-difluoroolefin is a multifunctional fluorine-containing synthon and is a core unit structure for improving performance in the fields of medicines, pesticides and materials. According to the method, an alpha-trifluoroolefin compound and various alkanes are taken as raw materials, and gem-difluoroallylation is directly realized under the conditions of acridine, alkali and illumination. The method has the advantages of simple preparation operation and wide substrate applicability, and contains various electron-withdrawing or electron-donating groups and various cyclic heterocyclic or non-heterocyclic alkanes. The method is mild in reaction condition, relatively high in yield and simple in subsequent treatment, and is a green chemical synthesis method with a relatively good application prospect.

The invention discloses a novel method for complete chemical synthesis of protein of a single-chain antibody fragment (scFv). The obtained product and a biological counterpart thereof are similar in structure and equivalent in function, but have the advantages that the product does not contain impurities, and the properties are more repeatable. The method comprises the general steps of: (a) respectively synthesizing subsequences (peptide fragments); (b) sequentially assembling the subsequences obtained in the step (a) according to the appearing sequence of the subsequences in the target scFv amino acid sequence; and (c) subjecting the assembled intact peptide molecules obtained in step (b) to oxidative folding and dialyzing the resulting product in a buffer solution.

To provide a highly polarized object containing a molecule, the target of high polarization by triplet DNP, to which a polarization source can be added and in which a sufficient longitudinal relaxation time can be achieved, and a manufacturing method thereof, a high polarization method and a high polarization device.SOLUTION: A highly polarized object 100 includes a first molecule 102, a second molecule 104, and a polarization source 108, where at least one of the first molecule and the second molecule is a target molecule whose nuclear spin is to be highly polarized by triplet DNP, a molecule that is not the target molecule out of the first molecule and the second molecule is a coformer molecule, the first molecule and the second molecule comprise a co-crystalline crystal structure including a binding part 106, the supramolecular synthon with a hexagonal structure, and the polarization source is arranged at a position to displace a part of the crystal structure.SELECTED DRAWING: Figure 1

The application discloses an asymmetric catalytic synthesis method of chiral 3-amino piperidine and derivatives thereof, and relates to the technical field of asymmetric catalysis, which comprises the following steps: (1) a mixture containing compound 2 and iodine is reacted to obtain intermediate 3; (2) a mixture containing intermediate 3 and a sulfilimine compound is subjected to a free radical asymmetric cross-coupling reaction to obtain chiral compound 4; (3) chiral compound 4 is subjected to desulfilimine protection to obtain intermediate 5; and (4) intermediate 5 is subjected to deprotection to obtain 3-amino piperidine; the intermediate 5 is a 3-amino piperidine derivative. The application is aimed at important synthesizers such as chiral 3-amino piperidine and derivatives thereof, and the synthesizers are rapidly synthesized through a free radical asymmetric cross-coupling method; a free radical asymmetric cross-coupling reaction catalyzed by copper and a chiral anion ligand is utilized to construct chiral 3-amino piperidine and derivatives thereof under mild conditions.

The invention provides a preparation method of an intermediate for preparing S-nicotine and a method for preparing S-nicotine by using the intermediate, and the chemical name of the intermediate is (4S)-4-((S)-1-phenylethyl) amino-4-(3-pyridyl)-1-butanol. The method for preparing nicotine by adopting the intermediate has the advantages that high-price reagents and synthons are not needed, the condition is mild, the work amount is small, the total synthesis of S-nicotine can be completed by introducing a chiral center through a key chiral reductive amination reaction, and the method is high in efficiency, low in cost, safe, reliable and capable of being applied to industrial production.

The invention discloses a method for preparing an ionic enamine compound from a pyridinium-alkyne monomer and application of the ionic enamine compound, belongs to the technical field of organic synthesis, and particularly relates to a method for preparing the ionic enamine compound by taking the pyridinium-alkyne monomer and an amine monomer as raw materials and carrying out alkyne-amine hydroamination reaction. The method can be carried out at room temperature without the action of a catalyst, the reaction efficiency is high, excellent regioselectivity and stereoselectivity are achieved, no by-product is generated in the reaction process, the atom economy is high, and the prepared ionic enamine compound contains ionic groups, is good in water solubility, contains heteroatoms and benzene rings in the structure, and can be used for preparing the ionic enamine compound. The compound has rich electrons, has a good application prospect in preparation of photodynamic drugs, photosensitizers, photodynamic antibacterial agents or biological imaging reagents, and can also be used as an effective synthon, that is, a nucleophilic reaction is further carried out, and compounds with more diversified structures are synthesized.

The present invention discloses a molecular reverse synthesis method, system, storage medium and terminal based on quantum graph convolution, belonging to the field of drug analysis. The structural information and chemical properties of the target product are represented in the form of a molecular undirected graph; each graph node and connection edge are mapped to a unique vector by using one-hot encoding; then the molecular graph node and connection edge information data are quantum encoded; a quantum graph convolutional neural network is constructed based on the encoded quantum graph, and the position of the predicted reaction center is output to obtain a synthon graph; a graph convolutional policy network is used to traverse the synthon graph, identify the atoms that need to be replaced or added and map them into an action vector, and decode the action vector to obtain the representation of the reactant. The present invention realizes the translation process from the product graph to the reactant graph, ensures the usability of the final reactant, solves the problems of large computational difficulty and unsatisfactory synthesis route prediction results in the current molecular reverse synthesis task, and provides a technical reference for future drug research and development.

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.

A method for training a model to estimate synthetic accessibility may be provided. A retrosynthesis-related synthetic accessibility model may be provided. A molecular structures database may be accessed. At least one molecular structure may be obtained from the molecular structures database with the model. The at least one molecular 5 structure may be virtually sliced into synthon-like fragments with the model. A frequency of the synthon-like fragments in natural molecules may be determined with the model. Molecular descriptors for the synthon-like fragments may be calculated with the model. An aggregated synthetic accessibility score for the synthon-like fragments may be determined with the model. The aggregated synthetic accessibility score for the synthon-10 like fragments may be stored in a database for the model.

The application provides a full-carbon [3+2] cycloaddition reaction, which is a conversion under mild photocatalytic conditions by taking an easily available aldehyde as a substrate and a perfluoroalkyl alkyne as a high-value C3 synthon. The method can modularly construct a series of multifunctional cyclopentanones which are important in structure and strong in synthetic practicability, and the products are provided with unique alpha-perfluoroalkenyl substituents. The reaction steps are excellent in economy and atom economy, the functional group compatibility is good, and the yield is medium. The reaction condition is mild, the operation is simple and high in efficiency, and the method shows the characteristics of wide substrate range and excellent functional group compatibility.

The present invention relates to the field of asymmetric catalysis and organic synthesis, and specifically provides a general method for generating axial chirality by means of a chiral companion strategy. The features and concept of the method are: a chiral aromatic tertiary amine compound without a nitrogen chiral center is subjected to intramolecular chiral oxidation to induce the formation of a new aromatic tertiary amine N-oxide (NO) chiral center. Due to the structural rigidity of the chiral aromatic tertiary amine N-oxide compound, when the steric hindrance of different substituents Rb and Rs connected to ortho positions of an aromatic ring is relatively large, the rotation of the aromatic ring is hindered, and new rotation-hindered axial chirality is generated while an aromatic tertiary amine chiral N-oxide center is formed. By means of the method and by regulating the structural and functional characteristics of the different substituents Rb and Rs, various axial chiral ligands, chiral small-molecule catalysts, pharmaceutical and agrochemical intermediates, and chiral synthons can be prepared. The present invention has important scientific and application values for the design, synthesis, and application of chiral ligands, chiral catalysts, especially ligands and catalysts containing axial chirality, and chiral compounds having special functions.