GENERAL STRATEGIES FOR THE SYNTHESIS OF INDOLE ALKALOIDS - TOTAL SYNTHESES OF (+/-)-RESERPINE AND (+/-)-ALPHA-YOHIMBINE
GENERAL STRATEGIES FOR THE SYNTHESIS OF INDOLE ALKALOIDS - TOTAL SYNTHESES OF (+/-)-RESERPINE AND (+/-)-ALPHA-YOHIMBINE
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DOI：
10.1021/ja00254a036
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发表时间：
1987-09-30
影响因子：
15
通讯作者：
GRZEJSZCZAK, S
中科院分区：
文献类型：
--
作者：
MARTIN, SF;RUEGER, H;GRZEJSZCZAK, S
吲哚类生物碱的简捷、全合成（.+-.）-利血平(1)和(.+-.)- α。-育亨宾(4)是通过应用分子内Diels-Alder反应的一般策略来完成的，该策略可以方便地构建包含目标天然产物的基本D/E环亚基的功能化氢异喹啉环体系。因此，三烯酰胺23的热裂解产生了环加合物24，它很容易由丙炔醇通过六个步骤组装而成。随后将24加工成关键中间体32，它包含利血平E环中所有五个连续的立体中心，只需要四个额外的步骤。D/E环亚基32的再功能化产生仲胺48，转化为（。+-。）-利血平(1)与6-甲氧基色氨酸溴依次烷基化，然后汞离子诱导氧化环化。不饱和内酰胺30是利血平全合成的中间体(1)，也是相关吲哚生物碱（。+-。）-。α的前体。育亨宾(4)。在这种情况下，30通过一系列简单的反应转化为双环胺60，再经过催化加氢和氢解生成仲胺61。61与色氨酸溴偶联，随后在标准条件下氧化环化得到(.+-.)-. α。育亨宾(4)。利用胺60作为合成新型生物碱（.+-）的中间体。19日,20-dehydro -.alpha。-育亨宾(5)不成功。
The concise, total syntheses of the indole alkaloids (.+-.)-reserpine (1) and (.+-.)-.alpha.-yohimbine (4) have been completed by the application of a general strategy that features an intramolecular Diels-Alder reaction for the facile construction of the functionalized hydroisoquinoline ring system that comprises the essential D/E ring subunit of the target natural products. Thus, thermolysis of the trienic amide 23, which was readily assembled in six steps from propargyl alcohol, delivered the cycloadduct 24. Subsequent elaboration of 24 into the key intermediate 32, which bears all five of the contiguous stereogenic centers present in the E ring of reserpine, required only four additional steps. Refunctionalization of the D/E ring subunit 32 provided the secondary amine 48, which was converted into (.+-.)-reserpine (1) by sequential alkylation with 6-methoxytryptophyl bromide followed by mercuric ion induced, oxidative cyclization. The unsaturated lactam 30, which was an intermediate in the total synthesis of reserpine (1), also served as a precursor to the related indole alkaloid (.+-.)-.alpha.-yohimbine (4). In the event, 30 was converted by a straightforward sequence of reactions into the bicyclic amine 60, which was subjected to catalytic hydrogenation and hydrogenolysis to afford the secondary amine 61. Coupling of 61 with tryptophyl bromide and subsequent oxidative cyclization under standard conditions afforded (.+-.)-.alpha.-yohimbine (4). Efforts to employ the amine 60 as an intermediate in a synthesis of the novel alkaloid (.+-.) 19,20-dehydro-.alpha.-yohimbine (5) were unsuccessful.