酰胺直接转化方法在(–)-Sedacryptine和(–)-Geissman-Waiss内酯合成中的应用

doi:10.6023/cjoc202408032

摘要/Abstract

酰胺是一类价廉易得的合成原料, 也是全合成重要的合成中间体. 由于酰胺在温和条件下的化学选择性直接转化有较高的步骤经济性, 因此具有重要的合成意义. 黄培强课题组于2010年报道了酰胺直接还原(脱氧官能化)反应, 随后又发展了一系列高化学选择性的酰胺还原与转化方法, 所发展的方法被国内外同行广泛地应用于多类生物碱和含氮药物的合成中. 此研究以该课题组发展的基于酰胺的脑文格(Knoevenagel-type)缩合反应及酰胺的化学选择性还原方法为关键步骤, 以简洁的合成路线(7步和4步)分别完成了生物碱(–)-Sedacryptine (1)的形式全合成和(–)-Geissman- Waiss内酯衍生物(3aS,6aS)-4-(4-甲氧基苄基)六氢-2H-呋喃[3,2-b]吡咯-2-酮(9)及其同系物(3aS,7aS)-4-(4-甲氧基苄基)六氢呋喃[3,2-b]吡啶-2(3H)-酮(10)的合成.

关键词: 酰胺, 脑文格反应, 铱-硼共催化还原, (–)-Sedacryptine, (–)-Geissman-Waiss内酯

Amides are not only a class of cheap and readily available feedstocks, but also important synthetic intermediates. Due to the high stability of amides, their transformation generally required multistep. The direct and chemoselective transformation of amides under mild conditions is highly desirable to approach step economy. However, it is quite challenging. In 2010, a general one-pot method for the direct conversion of lactams and amides into tertiary tert-alkyl-amines was developed by Huang et al. Since them, a handle of versatile methods for the chemoselective and direct transformation of amides have been developed from Huangʼs group in the last decade. The applicability of Huang’s amide-activation-annulation, reductive bis-alkylation of lactams/amides, direct transformation of secondary amides to nitriles, the reduction of amides with Tf₂O/ NaBH₄, among others, have been demonstrated by other research groups through the employment of Huangʼs methods to resolve their synthetic challenges. In this paper, formal total synthesis of (–)-sedacryptine (1) and total synthesis of (–)- Geissman-Waiss lactone derivative (3aS,6aS)-4-(4-methoxybenzyl)hexahydro-2H-furo[3,2-b]pyrrol-2-one (9) and (3aS,7aS)-4- (4-methoxybenzyl)hexahydrofuro[3,2-b]pyridin-2(3H)-one (10) have been achieved in seven steps and four steps. The strategy relies on the chemoselective one-pot Knoevenagel-type reaction of amides and iridium, and B(C₆F₅)₃ co-catalyzed deoxygenative reduction of tertiary amides developed from Huangʼs laboratory.

Key words: amide, Knoevenagel-type reaction, iridium and B(C₆F₅)₃ co-catalyzed reduction, (–)-Sedacryptine, (–)-Geiss- man-Waiss lactone

引用此文

徐业鹏, 阮义, 郑剑峰, 黄培强. 酰胺直接转化方法在(–)-Sedacryptine和(–)-Geissman-Waiss内酯合成中的应用[J]. 有机化学, 2025, 45(3): 988-995.

Yepeng Xu, Yi Ruan, Jianfeng Zheng, Peiqiang Huang. Synthesis of (–)-Sedacryptine and (–)-Geissman-Waiss Lactone by Applying Methods for the Direct Transformation of Amides[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 988-995.

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图/表 4

图式1. 酰胺的转化

Scheme 1. Transformation of amides

图式2. (–)-Sedacryptine (1)的逆合成分析

Scheme 2. Retrosynthetic analysis of (–)-sedacryptine (1)

图式3. (–)-Sedacryptine (1)的形式全合成

Scheme 3. Formal total synthesis of (–)-sedacryptine (1)

图式4. Geissman-Waiss内酯衍生物9和10的合成

Scheme 4. Synthesis of the derivatives of Geissman-Waiss lactone (9 and 10)

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