SYMMETRY-DRIVEN SYNTHESIS OF INDOLE ALKALOIDS - ASYMMETRIC TOTAL SYNTHESES OF (+)-YOHIMBINE, (-)-YOHIMBONE, (-)-YOHIMBANE, AND (+)-ALLOYOHIMBANE
SYMMETRY-DRIVEN SYNTHESIS OF INDOLE ALKALOIDS - ASYMMETRIC TOTAL SYNTHESES OF (+)-YOHIMBINE, (-)-YOHIMBONE, (-)-YOHIMBANE, AND (+)-ALLOYOHIMBANE
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DOI：
10.1021/ja00099a019
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发表时间：
1994-10-05
影响因子：
15
通讯作者：
TANOL, M
中科院分区：
文献类型：
--
作者：
AUBE, J;GHOSH, S;TANOL, M
报道了目标生物碱的全不对称合成。合成涉及对映体纯的（S，S）-1，3，3a，4，7，7a-六氢-2（H）-茚-2-酮7及其内消旋异构体5的制备。然后使用氧氮丙啶合成/重排方案将每种酮转化为扩环内酰胺。应用Bischler-Napieralski环结构沿着适当的官能团变换，分别从介观或C-2-对称酮中得到对映体富集的别育亨烷或育亨烷.衍生自（S，S）-酮的顺式-5，6-二乙酰氧基化合物（18）用作全合成更高度官能化的生物碱的起始原料。因此，含吲哚侧链的位点特异性插入通过立体选择性形成氧氮丙啶，然后通过其立体特异性重排来实现。该序列的选择性允许在C-17和C-18（育亨宾编号）处区分醇并合成Delta 18，19-育亨宾。使用标准化学方法将该α，β-不饱和酮转化为（-）-育亨宾或（+）-育亨宾。
Total asymmetric syntheses of the target alkaloids are reported. The syntheses involve the preparation of enantiomerically pure (S,S)-1,3,3a,4,7,7a-hexahydro-2(H)-inden-2-one 7 and its meso isomer 5. Each ketone is then converted into a ring-expanded lactam using an oxaziridine synthesis/rearrangement protocol. The applications of Bischler-Napieralski ring constructions along with appropriate functional group transformations afford enantiomerically enriched alloyohimbane or yohimbane from the meso- or C-2-symmetric ketones, respectively. A cis-5,6-diacetoxy compound (18) derived from the (S,S)-ketone served as the starting material for the total syntheses of the more highly functionalized alkaloids. Accordingly, a site-specific insertion of the indole-containing side chain was accomplished via stereoselective formation of an oxaziridine followed by its stereospecific rearrangement. The selectivity of this sequence allowed for the differentiation of alcohols at C-17 and C-18 (yohimbine numbering) and the synthesis of Delta 18,19-yohimbone. This alpha,beta-unsaturated ketone was converted into either (-)-yohimbone or (+)-yohimbine using standard chemistry.