METHODS FOR INDOLE ALKALOID SYNTHESIS - A STUDY OF THE COMPATIBILITY OF THE INDOLE 2,3-QUINODIMETHANE STRATEGY FOR THE SYNTHESIS OF 16-METHOXY-SUBSTITUTED ASPIDOSPERMA-TYPE ALKALOIDS - SYNTHESIS OF (+)- AND (-)-16-METHOXYTABERSONINE
METHODS FOR INDOLE ALKALOID SYNTHESIS - A STUDY OF THE COMPATIBILITY OF THE INDOLE 2,3-QUINODIMETHANE STRATEGY FOR THE SYNTHESIS OF 16-METHOXY-SUBSTITUTED ASPIDOSPERMA-TYPE ALKALOIDS - SYNTHESIS OF (+)- AND (-)-16-METHOXYTABERSONINE
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DOI：
10.1021/ja00215a039
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发表时间：
1988-03-30
影响因子：
15
通讯作者：
MAGNUS, P
中科院分区：
文献类型：
--
作者：
CARDWELL, K;HEWITT, B;MAGNUS, P
以4-甲氧基-2-硝基苯胺（5）为原料，经5步反应合成1-甲氧羰基-6-甲氧基-3-甲酰基-2-甲基吲哚（10），总收率28%。由10和2-（苯硫基）乙胺在用酰氯（±）- 12得到六环加成物14（64%）。通过在含有2，6-二叔丁基-4-甲基吡啶的甲苯中用三氟乙酸酐处理，将其转化为亚砜15，随后转化为七环加合物20。在没有这种受阻的布朗斯台德基地的情况下，15人被减少到14人。20的平均值给出α，.贝塔不饱和酰胺21，完成脱乙基系列。在手性乙基系列中，所需的[2.2.1]手性助剂22（X = Cl）由26合成，如方案III所述。制备了22的两种对映异构体。亚胺11与（+）-22缩合得到六氢吡喃31，其通过Pummerer顺序和逆Diels-桤木反应转化为α，贝塔不饱和酰胺34.脱硫和伴随的还原得到35，其中通过使用硫代内酰胺脱氢程序重新引入6，7-双键以提供38（X = S）。去除硫代酰胺基团并用Vilsmeier试剂取代得到3-醛40，其经氧化、甲基化和脱保护得到（-）-16-甲氧基他勃松宁（4）。使用（-）-22的相同序列给出4的对映体。
4-Methoxy-2-nitroaniline (5) is converted into 1-carbomethoxy-6-methoxy-3-formyl-2-methylindole (10) in an overall yield of 28% through five steps. The derived imine from 10 and 2-(phenythio)ethylamine on treatment with acid chloride (.+-.)-12 gave hexacyclic adduct 14 (64%). It was converted into sulfoxide 15 and subsequently to heptacyclic adduct 20 by treatment with trifluoroacetic anhydride in toluene containing 2,6-di-tert-butyl-4-methylpyridine. In the absence of this hindered Bronsted base, 15 was reduced back to 14. Thermolysis of 20 gave .alpha.,.beta.-unsaturated amide 21, completing the deethyl series. In the chiral ethyl series the required [2.2.1] chiral auxiliary 22 (X = Cl) was synthesized from 26, as outlined in Scheme III. Both enantiomers of 22 were prepared. Condensation of imine 11 with (+)-22 gave hexacycle 31, which was converted by the Pummerer sequence and retro-Diels-Alder reaction into .alpha.,.beta.-unsaturated amide 34. Desulfurization and concomitant reduction gave 35, in which the 6,7-double bond was reintroduced by using the thiolactam dehydrogenation procedure to provide 38 (X = S). Removal of the thioamide group and formylation with the Vilsmeier reagent gave the 3-aldehyde 40, which on oxidation, methylation, and deprotection provided (-)-16-methoxytabersonine (4). An identical sequence using (-)-22 gave the antipode of 4.