Synthesis of Spiromamakone A Benzo Analogues via Double Oxa-Michael Addition of 1,8-Dihydroxynaphthalene.

Abstract

Two benzo analogues of cytotoxic spiromamakone A, comprising carbon atoms with the same oxidation state and unsaturation degree as those of the natural products, are synthesized and biologically evaluated. Substitution of α,α'-dioxoketene dithioacetals, derived from 1,3-cyclopentanediones with protected (2-formylphenyl)magnesium bromide and 1,8-dihydroxynaphthalene, followed by deprotection, generated these analogues via an intramolecular aldol reaction. The cytotoxicity of benzo analogues and synthetic intermediates against cervical carcinoma HeLa cells shows the necessity of the 4-cyclopentene-1,3-dione moiety for biological activity.

• Authors: Hirokazu Tsukamoto, Shogo Hanada, Koichi Kumasaka, Noritaka Kagaya, Miho Izumikawa, Kazuo Shin-Ya, Takayuki Doi
• Journal: Organic letters (Org Lett) Vol. 18 Issue 19 Pg. 4848-4851 (10 07 2016) ISSN: 1523-7052 [Electronic] United States
• PMID: 27648608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)