The synthesis of novel cyclic beta-amino acids as intermediates for the preparation of bicyclic beta-lactams

Several derivatives of homopipecolic acid are prepared by alpha-amino alkyl ation of malonic acid with cyclic imines 6 and 7, These are prepared on a l arge scale and with different substitution patterns. The beta-amino acids 8 and 9 were formed in high yield and with remarkable diastereoselectivity i f chiral :imines are used as starting materials, The diastereoselectivity o f the amino alkylation leading to homopipecolic acid analogues is compared to those of thiazolidineacetic acids by epimerisation experiments. A method for resolution of the obtained racemic beta-amino acids by diastereomeric salt formation is described. The beta-amino acids 9 and 15 were converted i nto their corresponding carbacepham analogues 14 and isopenam 16. The isope nam endo-16 was selectively epimerised by mild basic treatment of the N/S-a cetal to give an exo-configured precursor of isopenicillin G.