Studies related to penicillins and cephalosporins. Part 5. A new relay synthesis of penicillin

Abstract

3-Azido-1-(1-benzyloxycarbonyl-2-p-methoxybenzylthio-2-methylpropyl)-4-methylthioazetidin-2-one (4) was converted into benzyl (±)-6-azido-6-epi-penicillanate (6), and its stereoisomer (7) was converted into benzyl (±)-6-azido-5-epi-penicillanate (9) and benzyl (±)-6-azido-penicillanate (10). The synthesis involved a regiospecific chlorinolysis of the two sulphide bonds in (4) and in (7), followed by reductive cyclization of the resulting dichloro-compounds with tin(II) chloride. 3-p-Methoxybenzylthiovaline was used as starting material for the preparation of the key compounds (4) and (7), by a route involving the construction of the β-lactam ring on the nitrogen atom of the amino-acid.