Inversion of configuration at C-8 in the olivanic acids: conversion into the thienamycins and other novel derivatives

Abstract

The inversion of stereochemistry at C-8 in the olivanic acids, MM 22383 (7) and MM 22381 (6), is described. The reaction of p-nitrobenzyl (5R,6S)-3-[(E)-2-acetamidovinylthio]-6-[(S)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (8) with diethyl azodicarboxylate, triphenylphosphine, and formic acid afforded the 6-[(R)-1-formyloxyethyl] derivative (17), which upon alkaline hydrolysis gave the 6-[(R)-1-hydroxyethyl] derivative (18). Hydrogenolysis of the p-nitrobenzyl ester (18) furnished the sodium salt of N-acetyldehydrothienamycin (15), the (8R)-epimer of the olivanic acid MM 22383 (7). The 3-(2-acetamidoethylthio)-analogue, MM 22381 (6), was converted into N-acetylthienamycin (14) by performing a similar series of reactions on its p-nitrobenzyl ester (10). The transformation of the ester (18) to bis-protected thienamycin (22), via the C-3 thiol (21), is also described. Reaction of the olivanic acid esters (8) and (10) with diethyl azodicarboxylate, triphenylphosphine and hydrazoic acid resulted in the formation of the 6-[(R)-1-azidoethyl] derivatives (27) and (28). Subsequent hydrogenolysis provided (5R,6R)-3-[(E)-2-acetamidovinylthio]-6-[(R)-1-aminoethyl]-7-oxo1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (29) and the 3-(2-acetamidoethylthio)-analogue (30).