A bioinspired Ugi/Michael/aza-Michael cascade reaction in aqueous media: natural-product-like molecular diversity.
A bioinspired Ugi/Michael/aza-Michael cascade reaction in aqueous media: natural-product-like molecular diversity.
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DOI：
10.1002/anie.201103567
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发表时间：
2011-09
影响因子：
--
通讯作者：
Soumava Santra;P. Andreana
中科院分区：
文献类型：
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作者：
Soumava Santra;P. Andreana
快速构建多样化和复杂的分子结构需要化学知识的环境，以应对合成挑战。[1-3]例如，具有季碳中心的生物相关螺环框架以区域和立体特异性方式从简单底物组装，多年来已经取得了实质性进展。[4]在这种情况下，多组分反应（MCR），伴随着涉及级联过程已成为强大的战略组装更高的有序结构。[5]这些反应可以在一次转化中依次产生多个立体中心[6]，从而绕过耗时且昂贵的纯化。[7]最终，从MCR的级联过程，其中构建复杂的分子结构的主题是从事战略，提供了一个重大的挑战，在现代有机化学。作为一个正在进行的研究计划的一部分，朝着开发独特的级联反应，使用MCR产生生物相关的，多样化的，小的，复杂的分子，我们特别感兴趣的螺环结构含有氮杂和/或氧杂螺[4.5]癸烷（1;方案1）。[8]因此，我们开始设计一种用于构建石蒜科生物碱（+）-普利卡明（2），[9]（+）-tazettine（3），[10]（+）-加兰他敏的合成策略（4; Reminyl，Razadyne，Nivalin），[11] and Erythrina alkaloid（+）-erythratinone（5;[12]方案1），因为这些和其他家族成员表现出抗胆碱能、抗肿瘤、抗癌、免疫抑制和镇痛特性。[13]此外，已知该家族的成员抑制各种细胞周期进展（例如，肿瘤进展中的G 0/G1期，HIV-1中的G2/M期），并已发现其在精神分裂症和阿尔茨海默病的治疗性治疗中的应用。[13]化合物2-5都具有四环含氮结构，其含有5，6，6-或5，7，6-稠合的氮杂螺环核，其支撑季碳中心，5是唯一的例外。在1957年，巴顿提出石蒜科生物碱都是由共同的双酚生物合成前体去甲颠茄碱（6）衍生而来，[14]
The rapid construction of diverse and complex molecular architectures requires a milieu of chemical knowledge poised for undertaking synthetic challenges.[1–3] As an example, biologically relevant spirocyclic frameworks possessing quaternary carbon centers that assemble in a regio-and stereospecific manner from simple substrates have seen substantial advancements over the years.[4] In this light, multicomponent reactions (MCRs) that concomitantly involve cascade processes have emerged as powerful strategies for assembling higher-ordered structures.[5] These reactions can sequentially generate multiple stereocenters in a single transformation,[6] thus bypassing time-consuming and costly purification.[7] Ultimately, strategizing cascade processes from MCRs, in which the theme of constructing complex molecular architectures is engaged, provides a substantial challenge in modern-day organic chemistry. As a part of an ongoing research program toward the development of unique cascade reactions using MCRs to generate biologically relevant, diverse, small, and complex molecules, we were particularly interested in spirocyclicarchitecture-containing aza-and/or oxaspiro [4.5] decanes (1; Scheme 1).[8] Thus, we embarked on devising a synthetic strategy for the construction of Amaryllidaceae alkaloids (+)-plicamine (2),[9](+)-tazettine (3),[10](À)-galanthamine (4; Reminyl, Razadyne, Nivalin),[11] and Erythrina alkaloid (+)-erythratinone (5;[12] Scheme 1), as these and other family members exhibit anticholinergic, antitumor, anticancer, immunosuppressive, and analgesic properties.[13] In addition, members of this family are known to inhibit various cell-cycle progressions (eg, Go/G1 phase in tumor progression, G2/M phase in HIV-1), and have found applications in the therapeutic treatment of schizophrenia and Alzheimer s disease.[13]Compounds 2–5 all possess tetracyclic nitrogenous structures containing a 5, 6, 6-or 5, 7, 6-fused azaspiro cyclic core that underpins a quaternary carbon center, with 5 as the lone exception. In 1957, Barton proposed that all the Amaryllidaceae alkaloids were derived from the common bisphenol biosynthetic precursor norbelladine (6),[14] which is assembled