A practical synthesis of (Z)-debromohymenialdisine.
A practical synthesis of (Z)-debromohymenialdisine.
复制标题
(Z)-去溴处女膜醛的实用合成。
DOI：
10.1021/jo991277o
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Horne,DA
中科院分区：
文献类型：
--
作者：
BarriosSosa,AC;Yakushijin,K;Horne,DA
(Z)-Debromohymenialdisine [(Z)-DBH (1)], first isolated1a in 1980 from the caribbean sponge Phakellia flabellata, is a biologically significant member of the “oroidin” family of sponge metabolites. 2 Its corresponding (E) isomer is also known, having been isolated in 1996 from the common shallow-water sponge Stylotella aurantium. 3 Recently, a number of reports centering on (Z)-DBH and related analogue hymenialdisine (2) 1b have appeared describing the modulation of protein kinase C and the proinflammatory transcription factor, nuclear factor κB (NFκB). 4 NFκB is believed to be involved in the regulated gene expression of the inflammatory enzyme, cyclooxygenase (COX-II). 4b Together, these proteins play important roles as mediators of inflammation associated with arthritis. In addition, DBH has been shown to slow joint deterioration and cartilage degradation associated with osteoarthritis in animal models and is currently under development as a promising new drug candidate. 5 At present, there is no known pharmaceutical agent for the treatment of osteoarthritis, which is the most common manifestation of arthritic disease. Ongoing investigations have reached the point where a practical synthesis of DBH is needed for preclinical/clinical trials. Only limited supplies are available from natural sources. To address this problem, we report6 a practical synthetic approach to (Z)-DBH (1) as well as the first synthesis of (Z)-3-bromohymenialdisine (3), a sponge metabolite from
