Total Synthesis of (-)-Cephalotaxine
Total Synthesis of (-)-Cephalotaxine
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DOI：
10.1021/jo00106a023
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发表时间：
1995
影响因子：
3.6
通讯作者：
Naohiro Isono;M. Mori*
中科院分区：
文献类型：
--
作者：
Naohiro Isono;M. Mori*
Cephalotaxine (1) is the major alkaloid of Cephalotaxus harringtonia var. drupacae. The possible antileukemic activity of harringtonine, homoharringtonine, isohar-ringtonine, and deoxyharringtonine, which are its ester derivatives, has stimulated numerous studies directed toward synthetic cephalotaxine (1). Thereby, several elegant total syntheses of racemic cephalotaxine have been achieved.* 1 We herein report the total synthesis of (—)-cephalotaxine by a short sequence of steps. The planning of the synthesis of (—)-cephalotaxine (1) was based on the following points. The unique skeleton, a l-azaspiro [4.4] nonane, fused benzazepine system, would be prepared by the reaction of 2 with stannyl anion generated from Me3SiSnBu3 and F~ as developed by us. 2 For the synthesis of optically active cephalotaxine, the optically pure starting material 2 would be obtained from D-(+)-proline via 5 by Seebach’s procedure. 3 The methylenedioxy group on the aromatic ring does not favor the cyclization of the seven-membered ring4 (Scheme 1). As expected, we were able to obtain compound 2a in optically active form. Namely, alkylation of 5, 3 prepared from D-(+)-proline, afforded compound 6 in good yield, which was converted into the vinyl iodide 7 by the usual method. 5 Hydrolysis of 7 with 10% sulfuric acid, 6 followed by treatment with Boc20 andthen CH2N2, gave compound 8. Deprotection of the Boc group with CF3-
