The total synthesis of nocardicin A.

We report here a total synthesis of nocardicin A. The antibiotic was obtained as a mixture of diastereoisomers that possessed approximately one quarter of the antibacterial activity of the naturally occurring material. Recently a new B-lactam antibiotic, nocardicin A, has been reported.1,2) This is the first example of a monocyclic B-lactam derivative having antimicrobial activity. We report here the synthesis of this antibiotic. Two syntheses of nocardicin A have thus far been reported.3,4) The synthesis of a hydro-xymethyl analog has also recently appeared.5) A. Synthetic Strategy The synthesis of nocardicin A can be visualized as a three part problem involving 1) synthesis of the side chain acid containing homoserine linked at the para position to the oxime derivative of phenyl-Scheme 1. Scheme 2. Synthesis of the B-lactam moiety.