A novel synthesis of the monobactam antibiotic carumonam

• Published in: Journal of organic chemistry Vol. 53; no. 23; pp. 5507 - 5512
• Main Authors: Manchand, Percy S, Luk, Kin Chun, Belica, Peter S, Choudhry, Satish C, Wei, Chung Chen, Soukup, Milan
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.11.1988; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Four membered ring; Nitrogen heterocycle
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00258a020

A novel synthesis of the monobactam 4, a precursor of the antibiotic carumonam (3), has been achieved via the epoxide methyl (2R,3S)-4-acetoxy-2,3-epoxybutyrate (10). The latter was prepared from calcium L-threonate in three steps and 85% overall yield. In a related study, ethyl (2R,3S)-4-hydroxy-2,3-epoxybutyrate (17) was prepared from L-(+)-tartaric acid [(2R,3R)-tartaric acid] in 45% overall yield. Treatment of the sodium salt derived from 10 or 17 with ammonia led to a stereo- and regiospecific opening of the oxirane ring to give 20, after esterification, amide formation, and protection of the amino group. Conversion of 20 into 4 was accomplished by selective protection of the primary hydroxy group with chloroacetyl chloride, mesylation, sulfonation with 2-picoline-SO3, and ring closure with potassium bicarbonate.