Synthesis and Acylation of Salts of L-Threonine β-Lactone: A Route to β-Lactone Antibiotics

Article abstract of DOI:10.1021/jo00003a062

The synthesis and N-acylation of β-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 deg C gives the corresponding β-lactones 8a and 8b, respectively, in 45-56 percent 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 β-lactone (9a) and its allo isomer 9b (65-92percent).Compound 9a is readily acylated by reagents such as acid chlorides (e.g., acetyl, benzoyl) and mixed anhydrides to afford N-acyl β-substituted β-lactones such as 10 (antibiotic SQ 26,517), 14, 15, and 16 in good yield (84-92percent).Reaction of β-lactones 8a, 8b, and 9a with HBr in acetic acid results in nucleophilic ring opening by bromide at the β-position to give pure isomers of 2-amino-3-bromobutanoic acid.