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

6-Vinyl (12) and (5R)- and (5S)-vinylproline (18, 19) analogues of ascomycin are synthesised starting from the known suitably protected (6S)-methoxy-9-hydroxy derivative (4) of ascomycin. The strategy involves hydrolytic cleavage of the C_ε-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_ε-N or C_δ-N bonds, followed by deprotection and oxidation.