SYNTHESIS AND ACYLATION OF SALTS OF L-THREONINE BETA-LACTONE - A ROUTE TO BETA-LACTONE ANTIBIOTICS

The synthesis and N-acylation of beta-lactones derived from L-threonine and L-allo-threonine were investigated. Treatment of N-[(o-nitrophenyl)sulfenyl]-L-threonine (7a) and N-[(o-nitrophenyl)sulfenyl]-L-allo-threonine (7b) with 4-bromobenzenesulfonyl chloride in pyridine at -43 to -0-degrees-C gives the corresponding-beta-lactones 8a and 8b, respectively, in 45-56% yields. These can be deprotected with thiophenol or p-thiocresol in the presence of p-toluenesulfonic acid to produce optically pure salts of L-threonine-beta-lactone (9a) and its allo isomer 9b (65-92%). Compound 9a is readily acylated by reagents such as acid chlorides (e.g., acetyl, benzoyl) and mixed anhydrides to afford N-acyl-beta-substituted-beta-lactones such as 10 (antibiotic SQ 26,517), 14, 15, and 16 in good yield (84-92%). Reaction of beta-lactones 8a, 8b, and 9a with HBr in acetic acid results in nucleophilic ring opening by bromide at the beta-position to give pure isomers of 2-amino-3-bromobutanoic acid.