专利号:US-2024035023-A1 优先权日:2022-06-24 标题 :Computer implemented method for engineering fluorinase enzymes for synthesis of fluorophenyl compounds 发明人:R PRAVIN KUMAR; G GLADSTONE SIGAMANI; L ROOPA; B K NAVEEN; SHETTY ANUJ J; M LIKITH 权利人:KCAT ENZYMATIC PRIVATE LTD 摘要:The present invention discloses a computer-implemented method for engineering fluorinase enzymes towards the synthesis of fluorophenyl compounds. Limited or no mechanistic details of fluorinase enzymes have hindered progress in understanding their catalytic mechanisms for synthesizing synthetic organofluorine compounds. Through a comprehensive computational screening process, specific methionine-sulfonium phenyl substrates, including [(3S)-3-amino-3-carboxypropyl][2,5-difluoro-4-(4-methoxy-2,4-dioxobutyl)phenyl]methylsulfonium, were designed and optimized using quantum chemical optimization techniques. This methodology uncovers crucial information on F— ion attack conformation and the catalytic mechanism of the substrate, leading to the formation of Methyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate. Furthermore, a protein sequence and 3D modeling-based enzyme screening process was employed to identify the most suitable enzyme for this substrate. The identified enzyme was then engineered using the mechanistic insights gained from the studies, resulting in improved substrate scope, stability and catalytic efficiency. This computer-based approach offers an efficient and precise alternative to traditional trial-and-error methods, advancing the field towards the successful synthesis fluorophenyl compounds.
专利号:WO-2006048893-A3 优先权日:2004-11-05 标 题:A process for synthesis of large particle size statin compounds 发明人:SURI SANJAY; SARIN GURDEEP SINGH 权利人:MOREPEN LAB LTD; SURI SANJAY; SARIN GURDEEP SINGH 摘要:This invention discloses a process for synthesis of with large size statin compounds comprising adding solution of desired statin compound either crystalline or amorphous form, optionally obtained from, their intermediates by known methods, in organic solvent to anti-solvent, under stirring, optionally the solvent was being evaporated, isolating the title compound by centrifugation followed by drying under vacuum. Specifically the process was directed to the synthesis of Atorvastatin calcium and Fluvastatin Sodium.
专利号:US-8269001-B2 优先权日:2005-10-05 标题 :Process for the synthesis of HMG-CoA reductase inhibitors 发明人:CASAR ZDENKO 权利人:CASAR ZDENKO; LEK PHARMACEUTICALS 摘要:A novel synthesis of statins uses Wittig reaction of a heterocyclic core of statin with a lactonized side chain already possessing needed stereochemistry. Any separation of diastereoisomers is performed early in the course of synthesis.
专利号:US-2007066835-A1 优先权日:2003-03-24 标 题:Process for the synthesis of amorphous atorvastain calcium 发明人:CZIBULA LASZLO; DOBAY LASZLO; PAPP EVA W; JUHASZ IDA D; BALINT SANDORNE 权利人:CZIBULA LASZLO; DOBAY LASZLO; PAPP EVA W; JUHASZ IDA D; BALINT SANDORNE 摘要:The invention relates to a new process for the synthesis of amorphous atorvastatin calcium, which consists of dissolving the salt of the formula (I) of atorvastatin acid formed with a basic amino acid (I); in a mixture of water and a water miscible organic solvent, adding an aqueous solution of a water soluble calcium salt to the solution and isolating the so obtained entirely amorphous atorvastatin calcium of high purity by filtration.
专利号:US-9085538-B2 优先权日:2010-07-26 标题:Process for the preparation of key intermediates for the synthesis of statins or pharmaceutically acceptable salts thereof 发明人:CASAR ZDENKO; STERK DAMJAN; JUKIC MARKO 权利人:CASAR ZDENKO; STERK DAMJAN; JUKIC MARKO; LEK PHARMACEUTICALS 摘要:The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.
专利号:US-2007015260-A1 优先权日:2002-03-14 标 题:Synthesis of synthons for the manufacture of bioactive compounds 发明人:WONG CHI-HUEY; LIU JUNJIE; DESANTIS GRACE; BURK MARK 权利人:SCRIPPS RESEARCH INST 摘要:The present invention is based on the discovery that 2-deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4) and variants thereof can be used to catalyze sequential asymmetric aldol reactions between a wide variety of donor and acceptor aldehydes. The reaction products typically contain at least two new stereogenic centers and can be produced in enantiomerically pure form. As such, DERA catalyzed asymmetric aldol chemistry can be exploited to produce synthons for the synthesis of a variety of bioactive molecules.