Synthesis of novel 2-oxo-4-thia-1-azabicyclo[3.3.0]oct-7-ene-8-carboxylic acid derivatives

Abstract

The bicyclic thiazolidinone-carbapenem analogues, 18, 19 and 37 have been prepared from thio-glycolamide 5 and 3-triphenylmethoxypropionaldehyde 7, via 2-(2-triphenylmethoxyethyl)thiazolidin-4-one 8.

Elaboration of the thiazolidin-4-one 8 to the phosphorane 11, followed by detritylation, oxidation, and cyclization provided the bicyclic ester 14, which could be oxidized to the sulfoxide 15.

Functionalization at the C-5 position of the thiazolidin-4-one required protection as the tetra-hydrothiazolo-1,3-oxazine 22, which upon reaction with lithium diisopropylamide, toluene-p-sulfonyl azide and acetic acid provided the azido derivative 23 in 76% yield. Reduction and acylation, followed by acid catalysed hydrolysis gave 2-(2-hydroxyethyl)-5-phenylacetamidothiazolidin-4-one 28, which was oxidized to the aldehyde 29. The aldehyde functionality was masked as the α,β-unsaturated ester 31 during the process of ylide construction. Regeneration of the aldehyde moiety could then be achieved by selective ozonolysis of phosphorane 34. The phosphorane-aldehyde 35 thus formed spontaneously cyclized to the bicyclic thiazolidinone ester 36.

Removal of the carboxylate protecting groups of the bicyclic thiazolidinone derivatives 14, 15 and 36 then provided the sodium salts of the carboxylic acids 18, 19 and 37, respectively.