Novel analogues of ascomycin with modifications in the amino acid unit through photochemistry:: the synthesis of 5,6-dehydroascomycin, SDZ ASQ 871

Irradiation of ascomycin la and its derivatives in MeOH, EtOH and propanol resulted in alkoxylation of the pipecolic acid moiety in the F-position with concomitant reduction in the tricarbonyl region leading to 6-alkoxy-9-hydroxy derivatives in high stereoselectivities and good yields. The products, after reoxidation of the C(9)-OH, afforded the 6-alkoxy analogues of the parent compounds. Elimination of MeOH from the photoproducts, followed by oxidation gave the corresponding 5,6-dehydro amino acid analogues. Similarly, starting from the proline analogue 7 modifications in the pyrrolidine moiety could be achieved. (C) 2004 Elsevier Ltd. All rights reserved.