Simple and condensed β-lactams. Part 9. Elaboration of the 3-(1-hydroxyethyl) side chains of potential intermediates of carbapenem antibiotics via the 2-methyl-1,3-dioxolan-2-yl group

Abstract

Deketalization of the trans compounds methyl and ethyl (2RS,3RS)-1-(2,4-dimethoxybenzyl)-3-(2-methyl-1,3-dioxolan-2-yl)-4-oxoazetidine-2-carboxylates (5b) and (5c), and of the cis[or (2RS,3SR)] isomer (6b) of the latter leads to 85 : 15 mixtures of the trans- and cis-compounds methyl (2RS,3RS)- and (2RS,3SR)-3-acetyl-1-(2,4-dimethoxybenzyl)-4-oxoazetidine-2-carboxylate (7a) and (8a), respectively of the corresponding ethyl esters (7b) and (8b). Sodium borohydride reduction of the mixture of the trans- and cis-esters (7b) and (8b) gives a mixture of the 1′-epimeric trans-compounds ethyl (2RS,3RS)-1-(2,4-dimethoxybenzyl)-3-[(1RS)- and (1SR)-1-hydroxyethyl]-4-oxazetidine-2-carboxylate (9b) and (10b). Similar mixtures of 1′-epimeric compounds of the types (9) and (10), carrying a variety of substituents attached to position 2 of their azetidine rings were obtained by successive deketalization and reduction of the corresponding trans-(5) and cis-(6) compounds or their mixtures, as well as by other methods. Ring closure of a mixture of the pair of the 1′-epimeric trans-compounds p-nitrobenzyl 2-diazo-4-{(2RS,3SR)-3-[(1RS)- and (1SR)-1-hydroxyethyl]-4-oxo-azetidin-2-yl}-3-oxobutanoates (9n) and (10n) gave a mixture of the 1′-epimeric compounds p-nitrobenzyl 6-[(1RS)- and (1SR)-1-hydroxyethyl]-2,7-dioxo-(3RS,5RS,6SR)-carbapenam-3-carboxylates (11) and (12) which was converted into a mixture (13) of the 1′-epimeric bis-protected thienamycin analogues p-nitrobenzyl 2-(2-formylaminoethylthio)-6-[(1RS)- and (1SR)-1-hydroxyethyl]-7-oxo-(5RS,6SR)-carbapen-2-em-3-carboxylates.