First stereoselective synthesis of serinol-derived malyngamides and their 1′-epi-isomers

A stereoselective synthesis of 1a {N-[(1R)-2-hydroxy-1-methoxy-methyl ethyl]-(4E,7S)-7-methoxy-4-eicosenamide} has been accomplished in 10 steps from 1-tetradecanol for the first time in 28% overall yield. The key steps involved the coupling reaction of a chiral alkyne with a protected bromide in the presence of t-BuLi, as well as the amidation reaction of (4E,7S)-7-methoxyeicos-4-enoic acid with (R)-methoxyamino alcohol. Acetylation of 1a finished the preparation of 1b {N-[(1S)-2-acetyloxy-1-methoxy-methyl ethyl]-(4E,7S)-7-methoxy-4-eicosenamide}. Their 1′-epi-isomers have also been synthesized with a similar strategy.