Synthesis of synvinolin: extremely high conversion alkylation of an ester enolate

Autor:	T. M. H. Liu, David Askin, Thomas R. Verhoeven, Ichiro Shinkai
Rok vydání:	1991
Předmět:	chemistry.chemical_classification Bicyclic molecule Organic Chemistry Keto–enol tautomerism Alkylation Medicinal chemistry chemistry.chemical_compound Hydrolysis chemistry Amide medicine Moiety lipids (amino acids peptides and proteins) Lovastatin Lactone medicine.drug
Zdroj:	The Journal of Organic Chemistry. 56:4929-4932
ISSN:	1520-6904 0022-3263
DOI:	10.1021/jo00016a023
Popis:	A 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 bis [(tert-butyldimethylsilyl) oxyl] butylamide 7. An extremely high conversion (99.7%) 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
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ea82ddd064611a40d59f76fe87e2e428 https://doi.org/10.1021/jo00016a023 Zobrazit plný text záznamu