An Expedient Synthesis of LAF389, a Bengamide B Analogue

Autor:	Lech Ciszewski, Thomas J. Blacklock, Wenming Liu, Xu David, Kapa Prasad, Kevin Vargas, Oljan Repic, Liladhar Murlidhar Waykole, Joanna Szewczyk, George T. Lee, Calienni John Vincent
Rok vydání:	2003
Předmět:	chemistry.chemical_classification chemistry Bengamide B Yield (chemistry) Organic Chemistry Organic chemistry Physical and Theoretical Chemistry Aldehyde Combinatorial chemistry Lactone
Zdroj:	Organic Process Research & Development. 7:856-865
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op0341162
Popis:	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, e-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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5cf6712c3af18cd5a7ea5c52697e1008 https://doi.org/10.1021/op0341162 Zobrazit plný text záznamu