An Expedient Synthesis of LAF389, a Bengamide B Analogue
Organic Process Research & Development2003Vol. 7(6), pp. 856–865
Citations Over Time
David D. Xu, Liladhar Waykole, John Calienni, Lech Ciszewski, George T. Lee, Wenming Liu, Joanna Szewczyk, Kevin Vargas, Kapa Prasad, Oljan Repič, Thomas J. Blacklock
Abstract
An optimized, convergent, safe synthesis of LAF389 (9), an anti-cancer agent analogous to bengamide B, is described. Starting from α-d-glucoheptonic (d-glycero-d-gulo-heptonic acid) γ-lactone (10), the lactone 15 was constructed in five steps. Major improvements were made in the preparation of the aldehyde precursor 14 and subsequent olefination to yield 15 via a modified Julia protocol. This olefination was significantly improved by using TMSCl as an additive. The second fragment of the drug substance, ε-caprolactam 7, was obtained in two one-pot operations from (5R)-5-hydroxy-l-lysine (1). Finally, opening 15 with 7 using sodium 2-ethyl hexanoate (Na-EH) gave 8, which on deprotection yielded LAF389.
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