Synthesis of 6-vinyl and 5-vinylproline analogues of ascomycin

Abstract 6-Vinyl ( 12 ) and (5 R )- and (5 S )-vinylproline ( 18 , 19 ) analogues of ascomycin are synthesised starting from the known suitably protected (6 S )-methoxy-9-hydroxy derivative ( 4 ) of ascomycin. The strategy involves hydrolytic cleavage of the C e –N bond of the pipecolic acid moiety, extension of the amino acid side chain by two or one carbon units, functional group manipulations, Pd-catalysed reinstallation of the C e –N or C δ –N bonds, followed by deprotection and oxidation.