The total synthesis of (+)-vedelianin has been accomplished in 18 steps from vanillin. Preparation of a key intermediate in nonracemic form through a Shi epoxidation has allowed determination of the absolute stereochemistry of the natural product as the (2S,3R,4aR,9aR)-isomer.
Bibliographical noteFunding Information:
We thank Dr. John A. Beutler (NCI–Frederick), Dr. Odile Thoisson, and Dr. Françoise Gueritte (ISCN CNRS, Gif-sur-Yvette, France) for sharing data on the activity of (+)-vedelianin in the NCI 60 cell line screen, Dr. John G. Kodet for providing the initial vanillin derivative, and Dr. Nolan R. Mente for providing phosphonate 18 . Financial support in the form of an ACS Division of Medicinal Chemistry predoctoral fellowship (to J.J.T.), a Shriner Fellowship from the University of Iowa (to J.J.T.), from the Roy J. Carver Charitable Trust, and the NIH (R41CA126020 via Terpenoid Therapeutics, Inc.) is gratefully acknowledged.