Asymmetric synthesis of a selective endothelin A receptor antagonist

Autor:	Zhiguo J. Song, Yoshimi Tsuchiya, Shigemitsu Okada, Takayuki Nemoto, Matthew M. Zhao, Atsushi Akao, Yoshiaki Kato, Koji Tomimoto, Kenji Niiyama, Hideki Jona, Toshiaki Mase
Rok vydání:	2002
Předmět:	chemistry.chemical_classification Ketone Stereochemistry Aryl Organic Chemistry Enantioselective synthesis Oxazoline Biochemistry Medicinal chemistry Formylation chemistry.chemical_compound chemistry Drug Discovery Pyridine Carbonylation Amination
Zdroj:	Tetrahedron. 58:3409-3415
ISSN:	0040-4020
DOI:	10.1016/s0040-4020(02)00280-6
Popis:	An asymmetric synthesis of a selective endothelin A receptor antagonist 1b is described. A highly substituted pyridine intermediate 11a was efficiently prepared via a mono-amination of inexpensive 2,6-dichloropyridine followed by a Vilsmeier formylation. Asymmetric conjugate addition of aryl lithium 14 to the chiral oxazoline 13 followed by hydrolysis afforded 15 in 90% ee. Pd(OAc)2/dppf catalyzed carbonylation followed by chemoselective addition of aryl lithium 18 gave ketone 19 . Diastereoselective reduction of the ketone with LS-Selectride® followed by concomitant activation of the resulting alcohol and cyclization gave the late intermediate 21 . Deprotection and purification by crystallization furnished the enantiomerically pure target molecule 1b in 10% overall yield from 11a .
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4d31d3a961ac6557655fed8240b8286b https://doi.org/10.1016/s0040-4020(02)00280-6 Zobrazit plný text záznamu Full Text from ScienceDirect