SYNTHESIS OF 3,5-DIHYDROXY-7-PYRROL-1-YL HEPTANOIC ACIDS

摘要

Atorvastatin and related 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids can be made by oxidation of a 3,5-dihydroxy-7-pyrrol-1-yl heptanol precursor from novel but readily accessible starting materials. Silylether-protected 7-amino-3,5-dihydroxy heptanoic acid esters undergo Paal Knorr reaction with 1,4-diketones to give valuable silylether-diprotected 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acid ester intermediates for preparing atorvastatin. The Paal Knorr reaction of ketal-proctected 7-amino-3R, 5R-dihydroxy heptanoic acid esters with 4-fluoro-alpha-(2-methyl-1-oxopropyl-gamma-oxo-N,beta-diphenylbenzenebutanamide occurs in high yield with few side products when it is conducted in a low boiling point ether.