A highly efficient synthesis of the erythrina and B-homoerythrina skeleton by an AlMe3-mediated domino reaction
A highly efficient synthesis of the erythrina and B-homoerythrina skeleton by an AlMe3-mediated domino reaction
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DOI：
10.1002/anie.200460283
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Tietze, LF
中科院分区：
文献类型：
--
作者：
El Bialy, SAA;Braun, H;Tietze, LF
开发高效、环保的合成方法是现代化学的重要任务。在这种情况下，多米诺骨牌的概念被证明是非常成功的。[1]在多米诺骨牌反应中，键和新的官能团被构建，这些键和新的官能团又在相同的条件下在随后的步骤中进一步反应，形成新的键和官能团。形成的键越多，产物的复杂性越高，多米诺骨牌反应的质量就越大。已经报道了过多的两步多米诺骨牌反应，但三步转化是例外。在这里，我们描述了一种新的多米诺骨牌反应，用于连续步骤构建三个键，使其能够有效地访问冬虫夏草和B-高红藻生物碱的骨架。刺参生物碱是一类广泛的、结构有趣的天然产物，具有广泛的生物活性。[3]这一家族的许多化合物显示出类似箭毒的活性，以及降压、镇静和中枢神经系统抑制的特性。[4]在多米诺骨牌概念的背景下，刺参和B-高红藻生物碱2a和2b的骨架的逆合成通过N-酰亚胺离子3a和3b以及金属酰胺4a和4b得到了胺5a和环己烯衍生物6a和6b(方案1)。中间体N-酰亚胺离子3可以通过在分子内将伯甲酰胺[5]的铝络合物与4中的乙酸烯醇酯部分加成，然后消除醋酸而形成。可以通过伯胺5与烯醇醋酸酯6的酯功能反应原位获得铝络合物。
The development of efficient and environmentally acceptable synthetic methods is an important task of modern chemistry. In this context the domino concept has proved to be very successful.[1] In domino reactions bonds and new functionalities are constructed, which, in turn, react further in subsequent steps under identical conditions to form new bonds and functionalities. The larger the number of bonds formed and the higher the complexity of the product is the greater is the quality of a domino reaction. A plethora of twostep domino reactions have been reported, but three-step transformations are the exception. Here we describe a novel domino reaction for the construction of three bonds in sequential steps that allows efficient access to the skeleton of the erythrina and B-homoerythrina alkaloids. The erythrina alkaloids [2] such as erysodine (1) are a widespread, structurally interesting class of natural products with extensive biological activity.[3] Many compounds of this family exhibit curare-like activity as well as hypotensive, sedative, and CNS depressant properties.[4]The retrosynthesis of the skeleton of the erythrina and B-homoerythrina alkaloids 2a and 2b within the context of the domino concept leads to the amine 5a and the cyclohexene derivatives 6a and 6b via the N-acyliminium ions 3a and 3b and the metalated amides 4a and 4b (Scheme 1). The intermediate N-acyliminium ions 3 could be formed by an intramolecular addition of an aluminum complex of the primary carboxamide [5] to the enol acetate moiety in 4 with subsequent elimination of acetic acid. The aluminum complex might be accessible in situ by reaction of the primary amine 5 with the ester function of the enol acetate 6.