Synthetic Studies on Penems and Carbapenems(￥3). Practical Preparation of (3R,4R)-4-Acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-one Derivatives from 6-Aminopenicillanic Acid

摘要

Preparation of optically pure (3R, 4R)-4-acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-o ne derivatives, which can be employed as starting materials for synthesis of carbapenem and penem antibiotics, was established in high efficiency from 6-amino-penicillanic acid (6-APA). 6-APA was diazotized and brominated to give 6, 6-dibromopenicillanic acid and its methyl ester was metalated with methylmagnesium bromide and condensed with acetaldehyde. The product, methyl 6-bromo-6-(1-hydroxyethyl)penicillanate was reduced with Zn-NH4Cl-NH4OH-acetone efficiently to give methyl 6-(l-hydroxyethyl)-penicillanate, which was protected either with モ,モ,モ -trichloroethoxycarbonyl group or with t-butyldimethylsilyl group. The thiazolidine rings of these compounds were cleaved by treatment of mercury(ケ) acetate in acetic acid and permangante in acetone in sequence to afford the desired optically pure final products.