Silvestrol

In support of the preclinical development of silvestrol at NCI, DSCB has completed the preparation of multigram quantities of the natural product silvestrol through total synthesis, using previously reported methodology¹ as the template for the scale-up work.

1. (a) Adams, Tim E, El Sous, Mariana, Hawkins, Bill C, Hirner, Sebastian, Holloway, Georgina, Khoo, Mui Ling, Owen, David J, Savage, G Paul, Scammells, Peter J, Rizzacasa, Mark A; Total synthesis of the potent anticancer Aglaia metabolites (-)-silvestrol and (-)-episilvestrol and the active analogue (-)-4'-desmethoxyepisilvestrol, J. Am. Chem. Soc. 2009, 131, 1607-16. (b) Liu, Tao, Nair, Somarajan J, Lescarbeau, André, Belani, Jitendra, Peluso, Stéphane, Conley, James, Tillotson, Bonnie, O'Hearn, Patrick, Smith, Sherri, Slocum, Kelly, West, Kip, Helble, Joseph, Douglas, Mark, Bahadoor, Adilah, Ali, Janid, McGovern, Karen, Fritz, Christian, Palombella, Vito J, Wylie, Andrew, Castro, Alfredo C, Tremblay, Martin R; Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors, J. Med. Chem. 2012, 55, 8859-78. (c) Gaudouin, B, Jones II, G, Porco Jr, J; A biomimetic approach to the rocaglamides employing photogeneration of oxidopyryliums derived from 3-hydroxyflavones, J. Am. Chem. Soc. 2004, 126, 13260-13621.