An asymmetric synthesis of synthetic intermediates to thienamycin and epithienamycins A and B

Abstract

An asymmetric synthesis for the synthetic intermediates to carbapenem antibiotics was examined via isoxazoline derivatives prepared by 1,3-dipolar cycloaddition between the nitrile oxide and menthyl crotonate. The (4S)-trans-azetidinone (14) having the antipodal configuration of thienamycin was synthesised in 16–20% e.e., while 85.3% e.e. of the (4R)-cis-azetidinone, possessing the same absolute configuration of epithienamycins A and B, was obtained by the same reaction procedure. The c.d. assignment of 3,4-dialkylated β-lactams is also described.