343 results about "Protecting group" patented technology

The invention discloses an oligonucleotide synthesis process of a sulfo-PMO structure. In the oligonucleotide synthesis process of the sulfo-PMO structure, the molecular structural formula of sulfo-PMO is shown in the specification. According to the invention, the molecular structure of thio-PMO is specifically limited, and the synthesis of nucleotide phosphate amide and (thio) phosphoric acid amide in the solid-phase synthesis oligonucleotide is carried out along the direction from 5'to 3 ', that is, in each cycle period, the O5'or O6' position of the nucleotide phosphate amide and (thio) phosphoric acid amide monomer is firstly subjected to coupling reaction, and then the protecting group is removed at the O3 'or N3' position, so that the oligonucleotide phosphate amide and (thio) phosphoric acid amide are obtained. And releasing active hydroxyl or amino / amido to enter the next cycle. The protecting group adopted by the sulfo-PMO molecule is consistent with the protecting groups of other nucleotides, so that the conversion rate of each step of coupling reaction can be conveniently detected on line.

The invention discloses a chemical-enzymatic coupling synthesis method of oseltamivir phosphate, which comprises the following steps: by taking monasic acid OS-01 as a substrate, sequentially carrying out S1 esterification, S2 ketalation, S3 selective ring opening, S4 TEMPO oxidation, S5 primary transaminase reaction, S6 acetylation, S7 secondary transaminase reaction and S8 phosphorylation reaction to obtain the final product oseltamivir phosphate OS-09. According to the method, the step of sodium azide required by a traditional route is avoided, the production safety and the industrialization possibility are enhanced, two different transaminases are used for respectively constructing different chiral centers, the steps of protecting groups and deprotecting groups on the traditional route are not needed, the overall route is short, the used chemical reagents are few, the yield is high, and the method is suitable for industrial production. The industrial requirements of environmental protection and low cost are met.

The invention discloses N-alkylated / sulfonated benzimidazole polyaryletherketone / polyaryletherketone sulfone with controllable grafting density as well as a preparation method and application of the N-alkylated / sulfonated benzimidazole polyaryletherketone / polyaryletherketone sulfone. The preparation method comprises the following steps: firstly, introducing a protecting group on a phenolic hydroxyl group of a bisphenol monomer containing a benzimidazole structure, then carrying out nucleophilic substitution reaction on alkyl halide / alkyl halide sulfonic acid and-NH, and then removing the protecting group to obtain an N-alkylated / sulfonated benzimidazole functionalized bisphenol monomer; copolymerizing the monomer, a bisphenol monomer and a difluoro monomer to obtain a polymer; alkyl or alkyl sulfonic acid is introduced to a benzimidazole ring, so that-NH bonds are passivated, a steric hindrance effect is formed, and gelation of the polymer under a high polymerization degree is avoided; by adjusting the molar ratio of the monomers, the retention stability of the functional groups can be effectively controlled, and compared with the traditional grafting on the polymer, the non-regulation of functionalization and the gelation of the polymer are effectively avoided.

The application provides a method for synthesizing triaminotriphenylmethane, which does not need to use a solvent, uses N,N'-dibenzylaniline and trialkoxymethane as synthetic raw materials, and makes N,N'-dibenzylaniline and trialkoxymethane undergo a Friedel-Crafts alkylation reaction, so as to avoid the generation of 2,4',4"-triaminotriphenylmethane isomers in a traditional synthesis method by using the steric effect of two benzyl protective groups, thereby obtaining 4,4',4"-tri(N,N'-dibenzylaminophenyl)methane with high selectivity. 4,4',4"-tri(N,N'-dibenzylaminophenyl)methane is further subjected to a debenzylation reaction under neutral conditions to form triaminotriphenylmethane. According to the chemical structural formula of the target product, the benzyl group as the protective group of the amino group is reduced under a neutral environment, and the benzyl group is removed, and the formed byproduct is only toluene, which not only ensures the high yield and high selectivity of the target product, but also is very beneficial to obtaining high-purity 4,4',4"-triaminotriphenylmethane, and conforms to the principle of green chemistry.

The application relates to a synthesis method of an anti-freezing glycopeptide polypeptide and belongs to the technical field of polypeptide drug synthesis. The method comprises the following steps: 2-CL-Resin is used as a carrier resin, under the condition of adding an activating agent, the carrier resin and alanine are coupled to obtain Fmoc-Ala-2-CL-Resin; according to the amino acid sequence of the anti-freezing glycopeptide, other amino acids are sequentially coupled through a solid-phase synthesis method; after a protecting group is removed and the carrier resin is cleaved, the anti-freezing glycopeptide crude peptide is obtained; and after purification, salt conversion and freeze-drying, the anti-freezing glycopeptide polypeptide is obtained. The method has the advantages of short synthesis period, low cost, easy post-treatment, few by-products, high product yield, facilitation of large-scale production of the anti-freezing glycopeptide, and considerable economic applicative value and wide application prospect.

The invention relates to an anti-epileptic polypeptide coupling medicine and a preparation method and application thereof, the polypeptide coupling medicine comprises an Fmoc protecting group, a permeation accelerating peptide and a cell penetrating peptide which are sequentially connected from the N end to the C end, and the permeation accelerating peptide is connected with an anti-epileptic medicine molecule. According to the invention, by fully utilizing the treatment requirements of epileptic seizure and the technical advantages of intranasal drug delivery, through the collaborative design of the protecting group, the functional polypeptide sequence and the anti-epileptic drug, the defects of poor brain targeting property, easy cyclization of a polypeptide carrier, low intranasal delivery efficiency and the like of the traditional anti-epileptic drug are overcome, non-invasive, efficient and low-toxicity epilepsy treatment is realized, and the application prospect is wide. And the preparation process is simplified, the clinical transformation requirement is met, and meanwhile, a new strategy is provided for non-invasive brain delivery of neuropeptide drugs.

This application discloses a linker and its preparation method. The linker includes pharmacophore P, pharmacophore Q, and deoxynucleotides and / or deoxynucleotide derivatives connecting pharmacophore P and pharmacophore Q. Pharmacophore P is obtained by removing the protecting group from group B, and pharmacophore Q is obtained by removing the protecting group from group X. Group B is obtained by chemically modifying the benzylquinolone carboxylic acid pharmacophore, and group X is obtained by chemically modifying the zenomeprazole pharmacophore. The linker is prepared by linking group B and group X with deoxynucleotides and / or deoxynucleotide derivatives to form the linker, including solid-phase synthesis technology. The method of this application can automatically synthesize molecular probes or bivalent drugs containing two pharmacophores, thereby replacing the traditional stepwise linking method, enabling efficient construction of screening libraries, and allowing control of the spatial distance and spatial orientation of the pharmacophores by adjusting the number and base arrangement of deoxynucleotides.

The invention belongs to the technical field of organic synthesis and cosmetics, and particularly relates to a synthesis method of caffeoyl tripeptide-1. According to the invention, caffeic acid and tripeptide-1 are used as raw materials, and a condensation reaction is carried out under mild conditions through a specific activation strategy and a protective group technology to generate a target product. The method has the advantages of simple steps, mild reaction conditions, high total yield, good product purity and the like.

The present application relates to a method for synthesizing leu-enkephalin by Fmoc method, which uses Fmoc-protected amino acid as monomer, and sequentially connects amino acid to resin. In the synthesis of leu-enkephalin, all the amino acids do not have any side chain protection group. The Fmoc protection group is removed by using a solution of 1.00 mol / L imidazole and 0.02 mol / L tricyclohexylphosphine in tetrahydrofuran, and finally leu-enkephalin is obtained by removing the resin with aqueous trifluoroacetic acid. The present application first uses imidazole and tricyclohexylphosphine as components of Fmoc deprotection agent, instead of traditional pyridine. The deprotection agent is not controlled by "controlled chemicals", is cheap and easy to obtain, is stable in nature, and is low in toxicity, volatility and corrosion. The deprotection agent has excellent Fmoc removal ability, does not cause phenolic ring acylation side reaction of tyrosine side chain, does not need any side chain protection, simplifies the production process of polypeptide, reduces the preparation cost of polypeptide, and provides great improvement space for the design of synthesis strategy of polypeptide containing basic sensitive side chain protection group.

The application discloses a preparation method of baricitinib, and belongs to the technical field of drug synthesis. The method comprises the following steps: firstly, 2-[1-(ethylsulfonyl)-3-azetidinyl]acetonitrile and 4-pyrazole boron pinacol ester are subjected to a Michael addition reaction to obtain 1-(ethylsulfonyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]-3-azetidine acetonitrile as an intermediate I; secondly, a protection group is introduced on the amino group of 4-chloropyrrolopyrimidine to obtain an intermediate II; finally, the intermediate I and the intermediate II are subjected to a Suzuki coupling process by adopting a method of combining a nickel pre-catalyst with a supporting ligand to obtain the baricitinib. The preparation method creatively realizes cross coupling of the baricitinib by adopting the cheap metal nickel as a catalyst, avoids the use of a heavy metal palladium catalyst, and has the advantages of low cost, low toxicity, small pollution, green environmental protection and the like.

The invention relates to a preparation method of a hyperbranched polymer containing phthalic dicarboxaldehyde, which comprises the following steps: dissolving a chain transfer agent, a monomer ADP containing a phthalic dicarboxaldehyde protecting group, dimethylacrylamide and azodiisobutyronitrile in tetrahydrofuran, and reacting for 8-24 hours at 70 DEG C in an inert atmosphere; cooling to normal temperature, adding trifluoroacetic acid, and continuously reacting for 1-3 hours; and stopping the reaction and precipitating, and then drying in vacuum to obtain the hyperbranched polymer containing o-phthalaldehyde. The hyperbranched polymer prepared by the invention can be efficiently cross-linked and fixed with sclera collagen, and is used for intervention treatment of myopia progress.

This invention discloses a method for synthesizing styrene-based photoresist resin, comprising the following steps: adding styrene and p-tert-butoxystyrene to a DES solvent, ultrasonically dispersing the mixture, and then rapidly adding an initiator under an air atmosphere to obtain a styrene-p-tert-butoxystyrene copolymer, i.e., a styrene-based photoresist resin, via anionic polymerization. The preparation method of this invention is simple and the process is easy to control. Using DES as the polymerization solvent allows the reaction to proceed efficiently under ambient air atmosphere. Furthermore, the hydrogen bond network in DES can form a specific interaction with the oxygen atom in the p-tert-butoxy group, resulting in a significant stabilizing effect on this acid-sensitive protecting group and effectively suppressing the removal of the protecting group and the resulting side reactions during anionic polymerization.

This invention discloses a microRNA-responsive 1,2-dioxane-based chemiluminescent compound, its dual-probe system, kit, synthesis method, and applications. The compound's core is an o-acrylate-substituted phenoxyadamantane-1,2-dioxane, with the phenolic hydroxyl group protected by an azide benzyl group. The two-component probe system constructed based on this compound comprises an azide-modified first probe and a phosphine-modified second probe, each complementary to different segments of the target microRNA. Hybridization brings the two probes closer, triggering a Staudinger reaction to remove the protecting group and activate the chemiluminescent signal. This probe system requires no enzyme amplification or nucleic acid extraction, achieves a detection limit of 1.37 fM, and a signal-to-noise ratio as high as 157-fold. It can be successfully used for real-time imaging of endogenous microRNA-21 in live cells, showing broad application prospects in early tumor screening, auxiliary diagnosis, and prognostic assessment.

A method for manufacturing a laminate having a surface modification layer and a semiconductor substrate, comprising: a first step of applying a surface modifier containing an organic compound (A) having a hydroxyl group protected with a deprotectable protecting group and a solvent (B) on a semiconductor substrate, and then performing firing to obtain a surface modification layer precursor; and a second step of thinning the surface modification layer precursor by contacting the surface modification layer precursor with a thinning liquid (X) to obtain a surface modification layer having a film thickness of 5 nm or less.

The present invention provides an adhesive composition and the like comprising: a compound that generates an acid by heating or / and irradiating with an active energy ray; and a hydrophilic polymer compound having, in the molecule, a protected hydrophilic group that is protected by a protecting group and that is deprotected by the acid, and a non-protected hydrophilic group that is not protected by the protecting group.

The application discloses a synthesis method of 3,3-difluorocyclopentylamine hydrochloride, and particularly relates to the technical field of chemical synthesis. The synthesis method comprises the following steps: taking 2-cyclopentenone and phthalimide as raw materials, and sequentially performing a Michael addition reaction, deoxygenation fluorination, removal of a phthaloyl protecting group, Boc protection and deprotection and salt formation reaction to obtain 3,3-difluorocyclopentylamine hydrochloride. The synthesis route and process design of the application are reasonable, the starting raw material is 2-cyclopentenone, the required reaction condition is mild, the post-treatment method is simple, the operability is strong, the raw material and reagent are cheap and easy to obtain, and the total yield can reach 43.6%, so the synthesis method has large-scale preparation value.

The present application relates to the technical field of compound synthesis, and in particular to a preparation method of amino acid-based lactam, comprising: A) reacting an alpha-amino acid and an alpha-hydroxy acid ester in a first solvent under the action of a first catalyst to obtain N-(hydroxyacyl)-amino acid ester; B) reacting the N-(hydroxyacyl)-amino acid ester in a second solvent under the action of a second catalyst to obtain amino acid-based lactam with a structure shown in Formula I; in Formula I, R1 and R2 are independently selected from one of hydrogen, a C1-C4 straight-chain or branched-chain aliphatic hydrocarbon group, a substituted or unsubstituted C6-C30 aryl group, a protected amino group, a protected carboxyl group, a protected hydroxyl group and a protected sulfydryl group; and the protecting group is one of an alkoxycarbonyl group, an acyl group and an alkyl group. The present application can solve the problems in the existing lactam synthesis process, such as high raw material risk, complicated process, and difficult product purification.

The invention provides a preparation method of a Vickaclara intermediate 2-(7-azaindole-5-oxy)-4-(4-((2-(4-chlorphenyl)-4, 4-dimethyl cyclohexene-1-) methyl) piperazine-1-) benzoic acid, which comprises the following steps: by taking a compound II, namely 1-((2-(4-chlorphenyl)-4, 4-dimethyl cyclohexene-1-) methyl) piperazine hydrochloride as an initial raw material, reacting at the temperature of 60-80 DEG C under the protection of nitrogen, thereby obtaining the Vickaclara intermediate 2-(7-azaindole-5-oxy)-4-(4-(2-(4-chlorphenyl)-4, 4-dimethyl cyclohexene-1-) methyl) piperazine-1-) benzoic acid. The key intermediate 2-(7-azaindole-5-oxyl)-4-(4-((2-(4-chlorphenyl)-4, 4-dimethylcyclohexene-1-) methyl) piperazine-1-) benzoic acid of the Venoclara bulk drug is prepared by taking 2-(7-azaindole-5-oxyl)-4-(4-(2-(4-chlorphenyl)-4, 4-dimethylcyclohexene-1-) methyl) piperazine-1-) benzoic acid as a raw material through hydrochloric acid removal, nucleophilic reaction, hydrochloride formation and deprotection reaction and adopting a proper purification method. The method does not need a noble metal catalyst, does not need column chromatography purification, is simple and convenient to operate and is suitable for industrial production.

The present invention relates to a monomer having a functional group, a heat-resistant polymer having a rigid main chain using same, and a manufacturing method therefor. Particularly, the present invention relates to a monomer having a pentafluorophenyl group of chemical formula 1, a heat-resistant polymer of chemical formulas 2 and 3 having the monomer of the present invention, and a manufacturing method therefor. According to the present invention, a novel polymer obtained by polymerizing a novel monomer of the present invention has a reactive group of reactive pentafluorophenyl, and thus may exhibit excellent reactivity and enable synthesis of polymers having an excellent polymerization degree by using a polyhydroxyalkylation polymerization method without a protective group. Due to such excellent reactivity, the polymer of the present invention can cause a nucleophilic substitution reaction under mild conditions, and thus an ion-exchange group, such as sulfonic acid or phosphonic acid, can be introduced under mild conditions through such a reaction. In addition, the novel polymer of the present invention has high heat resistance and chemical resistance and good tensile strength, and thus can be used as an engineering plastic. In addition, the novel polymer of the present invention can be imparted with ionic conductivity or other functionalities by introducing a phosphonic acid group or a sulfonic acid group into any one of fluoro positions of pentafluorophenyl of the polymer, and accordingly, may be used as an electrolyte membrane for a fuel cell or water electrolysis. [Chemical formula 1] [Chemical formula 2] [Chemical formula 3]

An object of the present invention is to provide a solid-phase carrier for nucleic acid synthesis, in which a nucleic acid and an adduct can be easily separated by HPLC in a case where the nucleic acid is synthesized using the solid-phase carrier for nucleic acid synthesis and the nucleic acid is cut out, a compound which serves as a linker of the solid-phase carrier, a compound which serves as a precursor of the linker, and a method for producing a nucleic acid using the solid-phase carrier. The compound according to the embodiment of the present invention is a compound represented by the following general formula (1).In the general formula (1), Ar represents a tri- to tetracyclic aromatic ring which may have a substituent, Z represents a hydrogen atom or a protective group eliminable by an acid, and R1 to R4 each independently represent a hydrogen atom, an alkyl group, or an alkoxy group.

The purpose of the present invention is to provide a method for reducing the amount of nucleoside phosphoramidite used by suppressing the residual amount of nucleoside phosphoramidite in a reaction vessel in a method for producing oligonucleotides. Disclosed is a method for producing an oligonucleotide, which comprises (a) removing a protecting group from a protected nucleoside in which the protecting group is bonded to a hydroxyl group, a thiol group or an amino group at the 3 '-position or the 5'-position, (b) bonding nucleoside phosphoramidite to the hydroxyl group, the thiol group or the amino group at the 3 '-position or the 5'-position of the nucleoside from which the protecting group has been removed in the presence of an activator, (c) sulfurizing or oxidizing the bond formed in step (b), and (d) blocking the hydroxyl group, thiol group or amino group at the 3 '-position or 5'-position that is not bonded in the nucleoside; wherein the capping in the step (d) includes an operation of bringing the nucleoside into contact with a capping solution for a predetermined time [T] (minute). The blocking liquid contains N-methylimidazole having a compounding ratio [N] (%) (wherein the compounding ratio is the ratio (%) of the normal-temperature capacity of the N-methylimidazole before compounding to the sum (100%) of the normal-temperature capacities of the reagents that are compounded as the blocking liquid component before compounding), and the product ([N] * [T]) of [N] and [T] is 0.5-3.0. The above-mentioned problem is solved by the above-mentioned method and the like.

The purpose of the present disclosure is to provide an amide-crosslinked amidite monomer which contains a guanine base and can contribute to a reduction in the amount of the amidite monomer used during oligonucleotide synthesis. The present disclosure relates to a crystal of an amide-crosslinked compound represented by formula (1). (In the formula, P1 represents a protecting group for a hydroxyl group and P2 represents a protecting group for an amino group.

The application belongs to the technical field of organic synthesis, and discloses a deprotection method of thioacetal or thioketals, which comprises the following steps: taking thioacetal or thioketals shown in formula-I as a reaction substrate, taking triiodine reagent shown in formula-II as an oxidant, adding into a mixed solvent of water and an organic solvent, and adding an acid as an activator to carry out a mixing reaction, so as to obtain aldehyde or ketone compounds shown in formula-III, and complete the removal of thioacetal or thioketals protective groups; wherein X in the thioacetal or thioketals is selected from S, O or N; R 1 , R 2 , R 3 are each independently selected from hydrogen, methyl, methoxy or halogen. Through the method of the application, the efficient removal of thioacetal or thioketals protective groups under mild conditions is realized by taking triiodine reagent as an oxidant. The reaction route of the method is as follows:

The invention discloses an epinephrine drug nitrosamine impurity as well as a preparation method and application thereof. According to the method, an epinephrine drug is taken as a raw material, hydroxyl is protected through a silane protecting group, the protected hydroxyl and a nitrosation reagent are subjected to a selective nitrosation reaction, and then the target nitrosamine impurity is obtained through a deprotection reaction. According to the method, the high-purity nitrosamine impurity of the epinephrine medicine can be prepared and used as a reference substance for qualitative and content detection of the nitrosamine impurity in the production process of raw materials and medicines, so that it is ensured that the epinephrine raw material medicine and preparations meet the medicinal standard; the method has important significance in improving the quality of epinephrine drugs and guaranteeing the medication safety.

The invention discloses a microRNA (Ribonucleic Acid) response type 1, 2-dioxetane chemiluminescent compound as well as a double-probe system, a kit, a synthesis method and application thereof. The parent nucleus of the compound is o-acrylate substituted phenoxy adamantane-1, 2-dioxetane, and a phenolic hydroxyl group is protected by an azido benzyl group. A two-component probe system constructed based on the compound comprises a first azide-modified probe and a second phosphino-modified probe, the first azide-modified probe and the second phosphino-modified probe are respectively complementary with different sections of target microRNA, the two probes are pulled close through hybridization, a schudinger reaction is triggered to remove a protecting group, and a chemiluminescence signal is activated. The probe system does not need enzyme amplification and nucleic acid extraction, the detection limit reaches 1.37 fM, the signal-to-noise ratio reaches up to 157 times, and the probe system can be successfully used for real-time imaging of living cell endogenous microRNA-21 and has wide application prospects in the fields of early tumor screening, auxiliary diagnosis and prognosis evaluation.

The invention relates to the technical field of high polymer materials, in particular to a high-toughness nylon material and a synthesis method thereof. The preparation method adopts a three-step strategy of'protection-polycondensation-hydrolytic conversion ', and comprises the following steps: firstly, reacting a 4-p-toluenesulfonyl aminophenol protective agent with a polyether amine prepolymer with an ester bond side chain to protect an ester bond; secondly, the protected prepolymer and dicarboxylic acid are subjected to efficient polycondensation at the temperature of 160-230 DEG C, and a high-molecular-weight nylon polymer is obtained; and finally, by controlling acid hydrolysis conditions, removing a protecting group, and converting an ester bond side chain into an active carboxylic acid side chain at the same time. The method breaks through the traditional synthesis bottleneck, and the prepared nylon material has excellent mechanical properties brought by high molecular weight and functionality endowed by carboxylic acid side chains, and has important industrial application value.

The present invention relates to methods for efficiently preparing ascarosides and related compounds. A method for preparing ascarosides includes providing a 1-O-substituted rhamnose as a starting material; forming a monosulfonate at the 3-OH position of the 1-O-substituted rhamnose; treating the monosulfonate with a hydride source to form a 1-O-substituted ascaroside. The formation of the monosulfonate can be advantageously performed on a 1-O-substituted rhamnose that has no hydroxyl protecting groups at the 2-OH position or the 4-OH position.

The invention discloses a solid-phase and liquid-phase combined synthesis method of tilpotide, and belongs to the field of chemical synthesis of polypeptide drugs. The method comprises the following steps: firstly, synthesizing a complete main peptide chain of the tiall peptide on a solid phase carrier, and protecting a side chain of lysine (Lys24) at the 24th site by adopting an orthogonal protecting group (Dde), so that side chain activated ester (Ecosanoic acid-gamma-Glu-AEA-AEA-OSu) can be specifically connected to an amino group of lysine (Lys20) at the 20th site, and the protecting group of the Lys24 can be selectively removed under a mild liquid phase condition to obtain crude peptide of the tiall peptide. Complex side chain modification is transferred from a solid phase to a liquid phase, the problems of steric hindrance and low connection efficiency are effectively solved, and the method has the advantages of being high in synthesis purity, few in side reaction, easy to amplify and the like and is suitable for industrial production.