123049-81-0Relevant articles and documents
Synthesis of Synvinolin: Extremely High Conversion Alkylation of an Ester Enolate
Askin, D.,Verhoeven, T. R.,Liu, T. M.-H.,Shinkai, I.
, p. 4929 - 4932 (1991)
An efficient process for the commercial preparation of the therapeutically important cholesterol lowering drug synvinolin (2: simvastatin, ZOCOR) from mevinolin (1: lovastatin, MEVACOR) is reported.The synthesis relies upon deactivation of the δ-lactone carbonyl toward enolization via conversion to the bisbutylamide 7.An extremely high conversion (99.7percent) ester enolate alkylation of 7 affords 8 and 9.Subsequent desilylation and intramolecularly assisted basic amide hydrolysis in the presence of the dimethylbutyrate ester moiety yields 12, which is lactonized to 2.The overall yield from 1 to 2 is 86percent.
A cost-efficient synthesis of simvastatin via high-conversion methylation of an alkoxide ester enolate
Thaper, Rajesh K.,Kumar, Yatendra,Kumar, S.M. Dileep,Misra, Satyananda,Khanna, Jag Mohan
, p. 476 - 479 (1999)
A cost-efficient synthesis of simvastatin (2), starting from mevinolin (lovastatin) (la) or its precursor mevinolinic acid (Ib), is reported. This synthesis involves the use of a new intermediate, lovastatin cyclopropylamide (3), eliminating two chemical steps of protection and deprotection of the open dihydroxy form of (la). Synthesis is based on the high-conversion methylation of an alkoxide ester enolate and involves only four chemical steps. Methylation reaction conditions have been optimized to get +~ 99.5% conversion. Process is economical on large-scale and product (2) is obtained in 85% overall yield.
For the preparation of simvastatin method
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Paragraph 0052; 0060, (2017/08/25)
The present invention discloses a simvastatin preparation method, which comprises using lovastatin and alkyl amine to prepare lovastatin amide, protecting the hydroxyl in the lovastatin amide molecules, carrying out methylation on the protected lovastatin amide to obtain protected simvastatin amide, carrying out deprotection, alkaline hydrolysis and ammonium salt forming on the protected simvastatin amide to obtain a simvastatin ammonium salt, and carrying out cyclization on the simvastatin ammonium salt to generate simvastatin. According to the present invention, the methyl cyclohexane is adopted as the methylation reaction solvent, such that the tetrahydrofuran consumption is reduced, the cost is reduced, the production safety is improved, and the solvent recovery and reuse process is simplified.
Functional Micelles for Hard Tissue Targeted Delivery of Chemicals
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, (2016/12/16)
Compositions and methods for targeting agents to hard tissue are provided.
METHODS FOR PREPARING STATIN COMPOUNDS BY LACTONIZATION
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Page/Page column 5-6, (2012/12/13)
A method for preparing a statin compound by lactonization is disclosed, which comprises the following step: lactonizing a compound of formula II into the compound of formula I in the presence of a strong acid catalyst and a dehydrant in a first solvent, wherein Z represents H, ammonium, or a metal cations; R1 is H or C1-C6 alkyl, preferably H or CH3, R2 is CH3, OH, CH2OH, CH2OC(O)R3, CH2OR3, or COOR4, preferably CH3 or OH, R3 and R4 are independently selected from the group consisting of H and C1-C6 alkyl.