Enantioselective synthesis of 5-LO inhibitor hydroxyureas. Tandem nucleophilic addition-intramolecular cyclization of chiral nitrones

被引：36

作者：

Lantos, I

Flisak, J

Liu, L

Matsuoka, R

Mendelson, W

Stevenson, D

Tubman, K

Tucker, K

Zhang, WY

Adams, J

Sorenson, M

Garigipati, R

Erhardt, K

Ross, S

机构：

[1] Department of Chemistry, SmithKLine Beecham Pharmaceuticals, King of Prussia, PA 19406

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1997年 / 62卷 / 16期

关键词：

D O I：

10.1021/jo9621736

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.

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页码：5385 / 5391

页数：7

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