912 results about "Tert-Butyloxycarbonyl protecting group" patented technology

The present invention relates to the synthesis of beta-tetrahydro carboline carboxylic acid and its nanoparticle preparation; liquid phase process of gradually grafting peptide to obtain protected tetrapeptide intermediate, which, after eliminating its Boc, is condensated with N-Boc-beta-tetrahydro carboline carboxylic acid and further HF treated to eliminate its protection to obtain the said compound; the nanoparticle of tetrahydro carboline carboxylic acid and the in-vitro and in-vivo activity of said compound in-vitro and in-vivo experiments show that the compound of the present invention has excellent activity of resisting blood platelet aggregation, effect of resisting cell adhesion and effect of resisting thrombus.

The invention relates to a method for synthesizing trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamine which is an intermediate for preparing an anticoagulation medicine Ticagrelor. The method provided by the invention mainly comprises the following steps of: synthesizing the trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamine protected by tertiarybutoxy carbonyl through carrying out a rearrangement reaction of DPPA (Diphenylphosphoryl Azide); then removing the protective group of the trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamine protected by the tertiarybutoxy carbonyl and then alkalifying to obtain the product. The whole reaction can be finished through a one-pot boiling synthetic method so that synthesizing steps and synthesizing time are greatly saved, the cost is effectively reduced and the yield is improved; and the method for synthesizing the trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamine has the very active meaning in the industrial production.

The present invention relates to the preparation of cyclic peptide, and is especially new Fmoc-solid phase process of preparing Eptifibatide. The new process is superior to liquid phase process, which has long synthesis period, and BOC solid phase process, which uses virulent and corrosive material. The technological scheme is that the Eptifibatide preparing process includes the following steps: eliminating Fmoc protection of Fmoc-Rink Amide AM resin to obtain H2N-Rink Amide AM resin; connecting various protective amino acids successively to obtain corresponding resin; eliminating Fmoc-protection radical and Kaiser test to detect reaction procedure; preparing S-triphenyl mercapto propionyl-N, N-ditert butyl oxycarbonyl-homoarginine with lysine; grafting S-triphenyl mercapto propionyl-N, N-ditert butyl oxycarbonyl-homoarginine; eliminating side chain protecting radical and resin to reduce into coarse product; and cyclization, oxidation, HPLC tracking purification to obtain pure product.

The invention relates to a synthesis method of amino-protecting glycine dipeptidase derivant. The amino-protecting glycine dipeptidase derivant is N-9-Fmoc glycine dipeptidase, N-Boc glycine dipeptidase and N-acetyl glycine dipeptidase. The invention has the technology that glycine dipeptidase is dissolved in 1-20% of inorganic aqueous alkali, and the organic solution of Fmoc-OSu or Boc2O or Ac2Ois dropwise added; reaction is finished within 1-12 hours, the yield of the product Fmoc-Gly-Gly-OH, Boc-Gly-Gly-OH and Ac-Gly-Gly-OH is between 80-95%, and the content of the product is above 99%. The invention has simple technology, easy industrialization and low cost. The product of the invention is the important raw material for synthesizing polypeptide compound.

The invention discloses a prolinol derivative induced chiral MOFs material with asymmetric catalysis, which belongs to the technical field of a chiral catalytic material. L-BCIP or D-BCIP is used as a chiral source; 5,5'-methylene diiso-phthalic acid, 4,4'-biphenyl acid, 3,3',4,4'-biphenyltetrazole acid or 4,4'-sulfonyl terephthalic acid is used as a connecting ligand; Ln3+ is used as a node; a three-dimensional hole channel structure is constructed by a hydrothermal method; the general formula is as follows: Ln<3+>+L+L-BCIP or D BCIP->Ln-L, wherein Ln<3+> is a rare earth metal ion; L is a connecting ligand; L-BCIP is L-N-tert-butoxycarbonyl-2-imidazole-1-pyrrolidine; and D-BCIP is D-N tert-butoxycarbonyl-2-imidazole-1-pyrrolidine. The material can be used as a heterogeneous catalyst used for an asymmetric silicon cyanation reaction; therefore, the catalyst can be recycled with a yield of 100% and ee value of 99%; and the chiral MOFs material has good application prospect in the aspects of synthesis of pure enantiomer compounds, synthesis of medical intermediates and the like. The material can be recycled after proper treatment.

The invention discloses a method for catalytically synthesizing an atazanavir intermediate, which comprises the following steps: preparing a magnetic modified mesoporous material, co-immobilizing a carbonyl reduction enzyme and a coenzyme in the magnetic mesoporous material, and catalyzing (3S)-3-(tert-butyloxycarbonyl)amino-1-chloro-4-phenyl-(2R)-butanone by using the immobilized enzyme to generate the (3S)-3-(tert-butyloxycarbonyl)amino-1-chloro-4-phenyl-(2R)-butanol intermediate. The method has the advantages of high recovery rate of the carbonyl reduction enzyme and coenzyme, high regeneration efficiency of the coenzyme, low cost, wide market prospects and the like.

The invention discloses a method for preparing chiral N-tert-butyloxycarboryl-3-hydroxypiperidine. The method comprises the following steps: a) enabling racemic 3-hydroxypiperidine and di-tert-butyl dicarbonate ester to react to generate racemic N-tert-butyloxycarboryl-3-hydroxypiperidine; b) oxidizing the racemic N-tert-butyloxycarboryl-3-hydroxypiperidine into racemic N-tert-butyloxycarboryl-3-piperidone under the action of an oxidizing agent; c) reducing the racemic N-tert-butyloxycarboryl-3-piperidone by using a ketoreductase into the chiral N-tert-butyloxycarboryl-3-hydroxypiperidine. Compared with the prior art, the method provided by the invention can be used to prepare the chiral N-tert-butyloxycarboryl-3-hydroxypiperidine with the optical purity of 99% by using the racemic 3-hydroxypiperidine as a raw material, in addition, the material is cheap and easy to get, the reaction condition is mild, the operation is simple and feasible, the production cost is greatly lowered, and great industrial application value is achieved.

The invention relates to a method for preparing compound palbociclib (shown as the formula I). A compound D (shown as the formula II) serves as a raw material, and a compound E (shown as the formula III) is obtained through a rearrangement reaction of alkenyl ether; then the compound E is subjected to t-butyloxycarboryl protection group removal under the acidic condition, and target product palbociclib is obtained; an R group in a compound D is selected from any one of a C1-C6 alkyl group, a C1-C6 halogenate alkyl group, C1-C6 hydroxyalkyl and a C1-C6 naphthenic base. The process procedure and operation steps are easy and convenient, prepared palbociclib is high in purity, and good popularization prospects are achieved.

The invention relates to a cabazitaxel crystal which is solvent-free and non-crystallization water crystal form of 7, 10-dimethoxy docetaxel or (2R, 3S)-3-tert-butoxycarbonyl amino-2-hydroxyl-3- phenylpropionic acid 4-acetoxyl-2 alpha-benzoyloxy-5 beta, 20-epoxy-1-hydroxyl-7 beta, 10 beta- dimethoxy-9-oxo-11-taxadiene-13 alpha-ester; and the cabazitaxel crystal is shown to be positioned at 4.3, 7.1, 8.7, 10.2, 10.9, 12.2, 13.8, 15.2, 16.4, 17.0, 17.6, 18.3, 19.2, 19.6, 20.3, 21.2, 23.1, 24.7, 26.1, 27.3, 29.3, 31.9, 32.5 and 35.8 degrees 2 theta characteristic peak by powder X ray diffraction (PXRD). The invention also discloses a preparation method of the cabazitaxel crystal. The cabazitaxel crystal is prepared under the condition of reduced pressure at the room temperature, and is high in yield and good in purity.

The invention relates to a new synthesis technology of anti-cancer drug Raltitrexed. The technology comprises the following steps: 1) using L-glutamic acid as raw material to perform esterification with alcohol under the action of halogenating agent and obtain L-glutamic acid diester hydrochloride; 2) using 2-amino-5-methyl-benzoic acid as raw material to prepare 6-bromomethyl-3,4-dihydro-2-methyl-4-oxo-6-quinazoline through cyclization, amination and bromination; 3) using 2-thienyl-propanedioic acid as raw material to prepare N-[5-[N-(tert-butoxycarbonyl)-N-methylamino]-2-thenoyl]-L-glutamic acid diethyl ester through nitrification, esterification, reduction, amino protection, N-methylation and device-esterification; 4) using L-glutamic acid diester hydrochloride and N-[5-[N-(tert-butoxycarbonyl)-N-methylamino]-2-thenoyl]-L-glutamic acid diethyl ester to prepare N-[5-(N-methylamino)-2-thenoyl]-L-glutamic acid diester through dehydrant condensation and deamination protection; and 5) using N-[5-(N-methylamino)-2-thenoyl]-L-glutamic acid diester and 6-bromomethyl-3,4-dihydro-2-methyl-4-oxo-6-quinazoline to perform condensation under the catalysis of alkali, recycling preparative chromatography, purifying, and performing de-esterification to obtain Raltitrexed.

The invention relates to a chiral preparation method for N-t-butyloxycarboryl-(4S)-(p-phenyl phenyl methyl)-4-amino-(2R)-methylbutyric acid. The chiral preparation method comprises the following step: enabling a compound (1) and hydrogen to react in the presence of Pd/C and (S-phenylethylamine), thereby preparing a compound (2-a) as shown in the specification. The chiral preparation method is simple in reaction condition, easy to operate, easy in obtaining reagents, and applicable to industrial production, the cost can be lowered as an expensive chiral catalyst is not used, and both the reaction efficiency is improved and the product purity is ensured.

The invention discloses a compound. The compound is a compound shown as a formula I or a stereoisomer, a geometric isomer, a tautomer, nitrogen oxide, hydrate, a solvate, a metabolite and a pharmaceutically acceptable salt of the compound shown as the formula I, wherein Cbz represents benzyloxycarbonyl; Bn represents benzyl; Boc represents tert-butoxycarbonyl. The compound has stable physiochemical properties; compared with XJB-5-131, the compound has the advantages of improved water solubility, stable physiochemical properties, good bioactivity, small medicinal dosage, improved in-vivo stability, high bioavailability, small side effect and prominent target anti-oxidization property; the compound can be used for effectively repairing oxidization injuries of mitochondria, and preventing or treating neurodegenerative diseases including age-related macular degeneration and the like. The formula I is shown in the description.

The invention discloses a star-shaped cationic polymer containing dendriform polylysine element, and a preparation method and application thereof. The method comprises the following steps: carrying out substitution reaction to introduce an azido group onto the C6 site of beta-cyclodextrin; carrying out coupling reaction on propargylamine and N,N'-di-tert-butoxycarbonyl-L-lysine, and carrying out repeated condensation and deprotection reactions to synthesize the alkynyl-containing dendriform polylysine; and coupling the two products by a click chemical process to obtain the star-shaped cationic polymer beta-CD-PLLD containing dendriform polylysine element. The polymer has the advantages of regular and easily controlled structure, single molecular weight distribution, favorable biocompatibility, biodegradability and the like, and is prospected to be widely used in the field of gene therapy.

The invention provides a novel synthesis method of hepatitis drug velpatasvir.Two intermediate compounds including a compound 4 and a compound III are utilized to synthesize the velpatasvir, the structures of the two compounds are as shown in the following formulas, wherein PG radical is t-butyloxycarboryl (Boc), carboxybenzyl (Cbz), acetyl, benzoyl or (S)-2-methoxyl acyl carbonyl amino-3-methyl-butyryl group (Moc-L-Valyl).

The invention discloses a synthesis method of a chirality covalent organic framework. The method includes the following steps that firstly, a chirality precursor and benzenetricarboxaldehyde are catalyzed by acetic acid under the inert atmosphere to react and generate a solid product, wherein the structural formula of the chirality precursor can be seen in the description, and Boc is t-butyloxycarboryl; secondly, t-butyloxycarboryl is removed from the solid product obtained in the first step to obtain the chirality covalent organic framework material. The chirality covalent organic framework is successfully synthesized, has a large specific area and a regular pore structure, has good catalytic activity and circulation for the asymmetric Aldol reaction of ketone and aldehyde, and is a good multiphase chirality catalyst, and the application range of the molecular sieve material in the field of chirality catalysis is greatly expanded.

The invention discloses a preparation method of an NEP (neutral endopeptidase) inhibitor intermediate, further discloses a selective reduction preparation method of the NEP inhibitor intermediate (2R, 4S)-5-([1,1'-biphenyl]-4-yl)-4-((t-butyloxycarboryl)amino)-2-methylpentanoic acid in presence of a chiral ligand, and particularly discloses a diastereoselective hydrogenation synthetic method with hydrogen under the condition of presence of a transition metal catalyst and the chiral ligand. The metal catalyst used in the method is cheap, the chiral ligand is obtained easily, high yield is realized, a high-purity product is produced preferably, and the product with the proportion of diastereoisomers being 90:10 is produced preferably.

The invention relates to a preparation method of polyether amine. In the structure of polyether amine, the main chain is polypropylene oxide, polyethylene oxide, polytetrahydrofuran or a copolymer of polypropylene oxide, polyethylene oxide and polytetrahydrofuran; and one end of the main chain is hydroxyl, and the other end of the main chain is an alcohol amine compound terminated end having a H2N-R-O-H structure. Polyether amine is prepared by the following steps: (1) protecting the amino of the alcohol amine compound by using BOC (tertbutyloxycarbonyl) and maintaining hydroxyl to obtain BOC-NH-R-OH; (2) in the catalysis of strong base or double-metal cyanide, by using BOC-NH-R-OH, initiating polyethylene oxide, polypropylene oxide, tetrahydrofuran or the mixture of polyethylene oxide, polypropylene oxide and tetrahydrofuran to react for ring opening polymerization; and (3) under the acidic condition, carrying out BOC deprotection reaction to obtain polyether amine. According to the invention, polyether main chains having different hydrophilic properties can be obtained by regulating the ratio of polypropylene oxide to polyethylene oxide to polytetrahydrofuran in the polyether chain; and one end of the polyether chain contains the amino, thus the amino can provide strong hydrophilic property after acidification. Polyether amine prepared by using the method can be applied to the fields of a surfactant, a flocculant, textile dyeing and finishing auxiliary, electrophoretic paint and the like.

The invention discloses a synthesizing method of Alikelun of hypertension proteinogenase inhibitor, which comprises the following steps: adopting (1S, 4S, 2'S)-(4-benzyloxy methyl-2-hydroxy-1-{2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbonic tert-butyl as raw material; catalyzing; hydrogenating; removing benzyl; separating two R and S-typed diastereomers through column chromatography; obtaining (1S, 2S, 4S, 2'S)-(2-hydroxy-4-methylol-1-{2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbonic tert-butyl ester; oxidizing into (1S, 3S, 1'S, 4'S)-{1-(4-isopropyl-5-oxo-tetrahydrofuran-2-radical)-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-amyl}-carbonic tert-butyl ester; proceeding amide ester exchange to obtain (1 S, 3S, 1'S, 4'S)-(4-(2-amino formyl-2-methyl-propyl amino formyl)-2-hydroxy-1-{2-[4-methoxy-3-(3-methoxy-propoxy-benzyl]-3-methyl-butyl}-5-methyl-hexyl) carbonic tert-butyl ester; removing terbu-carbonyl to produce Aliskiren.

A pentazane derivative intermediate, its production and use are disclosed. PNZ expresses p-nitrocarbobenzoxy, R represents Ac(acetyl) or-H. It is simple and has no side reaction. It can be used for donippenan.

Disclosed are compounds having the structure:

wherein Z is —OH or —O•; and

A is:

wherein

• • • X and Y are independently NR₁ or O, where
    • R₁ is H or C₁-C₄ alkyl; and
    • R₂ is H, C₁-C₄ alkyl or t-butoxycarbonyl,
    • wherein W is C₃-C₄ alkynyl; and
    • R₁ is H or C₁-C₄ alkyl, or
    • wherein R₁ is H, C₁-C₄ alkyl, or C₃-C₄ alkynyl; and
      • R₃ is H, OH, O(C₁-C₄ alkyl), or a halogen,

optically active enantiomers, pharmaceutically acceptable salts of the compounds, pharmaceutical compositions containing such compounds or salts, and processes for their preparation. The subject invention also provides methods of alleviating symptoms of neurologic, autoimmune, and inflammatory disorders caused by the presence of reactive oxygen species, methods of preventing oxidation of lipids, proteins, or deoxyribonucleic acids on a cellular level, and methods of protecting human red blood cells from lysis by O₂ radicals.

A process for the preparation of taxanes comprising

wherein R is a tert. butoxycarbonyl or benzoyl group; PMP is p-methoxyphenyl group; G₁ is acetyl group; G₂ is haloacetyl group comprising

• • a) protecting the C-7 hydroxyl group of 10-deacetylbaccatin III with haloacetyl chlorides and then acetylating the C-10 hydroxyl group with acetyl chloride to obtain a protected 10-deacetylbaccatin III (1);
  • b) subjecting the protected 10-deacetylbaccatin III (1) to coupling with an oxazolidine-5-caboxylic acid of formula 2

wherein R is tert. butoxycarbonyl or benzoyl; PMP is p-methoxyphenyl group in the presence of a condensation agent and an activating agent to obtain C-13 esters of formula 3;

c) treating the coupled products 3 with weak acidic medium to open the oxazolidine ring to obtain intermediates of formula 4;

wherein R is a tert. butoxycarbonyl or benzoyl group; G₁ is acetyl group; G₂ is haloacetyl group

d) subjecting the intermediates of compound 4 to selective deprotection of haloacyl group in the presence of acetyl group under mild alkaline condition at −20 to +40° C. for 6-24 h in the presence of ammonia or aliphatic amine or aromatic amines or their combination to obtain paclitaxel or docetaxel.