Total Synthesis of Neurymenolide A

Key words

neurymenolide - α-pyrones - alkyne metathesis - gold - molybdenum

Significance

Neurymenolide A is an unusual α-pyrone macrolide that was isolated in 2009 from the Fijian red alga Neurymenia fraxinifolia, exhibiting a broad scope of biological activity. This work represents the first total synthesis of the natural product and features a series of remarkably selective transition metal-catalyzed transformations to build up the highly sensitive cyclophane scaffold.

Comment

The route is based on a novel gold-catalyzed pyrone synthesis that allowed for ­selective alkyne activation within intermediate F. α-Pyrone H was subjected to efficient alkyne meta­thesis to construct macrocycle J. Neurymenolide A acetate (K) exists as a mixture of interchanging atropisomers and the synthetic material obtained was identical to a sample derived from natural sources. Deprotection of K led to rapid degradation.