15 D-グルコサミンを利用するカルバペナムの合成研究 : (+)-チエナマイシンの合成

抄録

The chiral synthesis of (+)-thienamycin (1) starting with readily available D-glucosamine (3) has been described. Protected glucosamine 4 was submitted to photo-induced reductive deacetoxylation to give the 3-deoxyglucosamine derivative 5, which was then transformed into aldehyde 9 as shown (Scheme 2). Homoaldehyde 11 obtained from 9 via the Wittig reaction was oxidized and then hydrolyzed with alkali to give β-amino acid 14. The amino acid provided β-lactam 15 by treatment with (PyS)_2-Ph_3P. After N-silylation of 15, the hydroxyl group in the product 16 was reductively removed to give 18, and the hydroxyethyl side chain was introduced on its β-lactam ring by condensation with acetaldehyde yielding 6S,8R-isomer 19a as the major product, along with other diastereomers 19b〜d (Scheme 3). The undesired diastereomers 20b〜d, after O-silylation of the reaction mixture, were separated from the major product 20a and the former isomers were effectively recycled to the desired alcohol 19a as shown. The bis-silylated β-lactam 20a was debenzylated and regioselective oxidation of the resulting diol 22 by Pt-catalyzed autoxidation afforded hydroxy acid 23 (Scheme 4). The benzyl ester of 23 was oxidized to β-keto ester 25 ([α]_D-48.5°), which was spectroscopically identified as the known key intermediate for (+)-thienamycin (1).