A NEW SYNTHETIC ENTRY TO PENTACYCLIC STRYCHNOS ALKALOIDS - TOTAL SYNTHESIS OF (+/-)-TUBIFOLIDINE, (+/-)-TUBIFOLINE, AND (+/-)-19,20-DIHYDROAKUAMMICINE
A NEW SYNTHETIC ENTRY TO PENTACYCLIC STRYCHNOS ALKALOIDS - TOTAL SYNTHESIS OF (+/-)-TUBIFOLIDINE, (+/-)-TUBIFOLINE, AND (+/-)-19,20-DIHYDROAKUAMMICINE
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DOI：
10.1021/jo00313a017
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发表时间：
1990-12-21
影响因子：
3.6
通讯作者：
BOSCH, J
中科院分区：
文献类型：
--
作者：
AMAT, M;LINARES, A;BOSCH, J
提出了一种新的五环马钱子生物碱的合成方法。 它包括通过吲哚3-位上的环化从包含生物碱的环ABCD的适当N-取代四环系统闭合五元E环。 通过亚磺酰基乙酰胺4和6的Pummerer重排，从氯乙酰胺12或从双（甲硫基）乙酰胺10 b（环外酰胺羰基）进行关键环化的尝试导致失败。 在第一种情况下，分别以良好的产率形成二硫代缩醛9和10。 从醇13或从吲哚失活的缩醛15和二硫代西缩醛18的环化也是不成功的：从最初形成的氧鎓或硫鎓中间体16得到非环化产物。 用DMTSF处理N-未取代的吲哚二硫缩醛23，环化反应以49%的产率令人满意地完成。 将所得的五萜类化合物25转化为20-脱乙基tubifolidine（27）。 从仲胺32a制备的二硫缩醛41 a进行类似的处理，得到五肽42 a，由其合成生物碱tubifoline、tubifolidine和19，20-二氢阿库米辛。
A new strategy for the synthesis of pentacyclic Strychnos alkaloids has been developed. It consists in the closure of the five-membered E ring by cyclization upon the indole 3-position from a suitably N-substituted tetracyclic system embodying rings ABCD of the alkaloids. Attempts to effect the key cyclization either by Pummerer rearrangement of sulfinylacetamides 4 and 6, from chloroacetamide 12, or from bis(methylthio)acetamide 10b (exocyclic amide carbonyl group) resulted in failure. In the first case dithioacetals 9 and 10, respectively, were formed in good yields. Cyclization from alcohol 13 or from the indole-deactivated acetal 15 and dithiocetal 18 were also unsuccessful: noncyclized products coming from the initially formed oxonium or thionium intermediates 16 were obtained. Cyclization was satisfactorily accomplished in 49% yield by treatment of the N-unsubstituted indole dithioacetal 23 with DMTSF. The resulting pentacycle 25 was converted to 20-deethyltubifolidine (27). A similar treatment from dithioacetal 41a, prepared from the secondary amine 32a, afforded pentacycle 42a, from which the alkaloids tubifoline, tubifolidine, and 19,20-dihydroakuammicine were synthesized.