First Total Synthesis of Naturally Occurring (−)‐Nitidon and Its Enantiomer

The first total synthesis of naturally occurring (−)‐nitidon and its enantiomer is reported. The best of the routes investigated for preparation of these enantiomerically pure compounds involves a modification of the Cadiot−Chodkiewicz reaction and the Sharpless asymmetric epoxidation of an (E)‐2‐ene‐4,6‐diyn‐1‐ol as key steps and proceeds in five steps and 18% overall yield. Both enantiomers of nitidon and some related 6‐(1,3‐diyn‐1‐yl)‐2H‐pyran‐2‐ones have been found to exhibit significant cytotoxic activity against human cancer cell lines in vitro. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)