Abstract
(1__R__,5__S__,6__S__)‐2‐ [(3__S__,5__S__)‐5‐Dimethylaminocarbonylpyrrolidin‐3‐ylthio]‐6‐ [(1__R__)‐1‐hydroxyethyl]‐1‐methylcarbapen‐2‐em‐3‐carboxylic acid trihydrate (SM‐7338), a novel 1 β‐methyl carbapenem antibiotic, was labeled with carbon‐14 at the C3 position of the carbapenem nucleus for use in metabolic studies. The synthesis was achieved according to the scheme illustrated in Fig. 3. Selective esterification of [2‐^14^C]malonic acid (2) with 4‐nitrobenzyl bromide (3) gave its monoester (4). Condensation of the magnesium salt of 4 with the imidazolide derived from the azetidinone carboxylic acid (5) provided the β‐keto ester (6), which was desililated with hydrochloric acid to give the alcohol (7). Treatment of 7 with carboxybenzenesulfonyl azide followed by decomposition of the resulting diazo intermediate (8) in the presence of a rhodium catalyst produced the bicyclic keto ester (9). Reaction of 9 with diphenyl chlorophosphate in the presence of N,N‐diisopropylethylamine and subsequent displacement reaction of the vinyl phosphate (10) with mercaptopyrrolidine (11) gave bis‐protected SM‐7338 (12). Catalytic hydrogenolysis of 12 afforded [carbapenem‐3‐^14^C]‐SM‐7338 (1). The overall yield of 1 was 5.8% from 2.