Biomimetic total synthesis of gambogin and rate acceleration of pericyclic reactions in aqueous media
Biomimetic total synthesis of gambogin and rate acceleration of pericyclic reactions in aqueous media
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DOI：
10.1002/anie.200462211
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Wartmann, M
中科院分区：
文献类型：
--
作者：
Nicolaou, KC;Xu, H;Wartmann, M
Gambogin（1，方案1）具有不寻常的分子结构，并对HeLa和HEL细胞系表现出细胞毒性（MIC：分别为6.25和3.13 μg mLA ± 1）。[1]1996年从Garcina hamburyi的藤黄树脂中分离出来，这种天然存在的物质为新的合成技术和生物工具的开发提供了有趣的合成挑战和机会。在此，我们报告了一种仿生[2]的全合成方法[3]，并观察到在质子溶剂中，特别是在水中，Claisen重排和Claisen/Diels-Alder级联反应[4]的急剧速率加速。我们对gambogin分子的逆合成计划（1），其与forbesione和lateriflorone [5]的相似性影响了我们的想法，如方案1所示。因此，在环A（苯并吡喃环，非对映异构体的混合物）上应用逆克莱森重排[6]，解开了炔属苯型化合物2，其可以从3a通过O-
Gambogin (1, Scheme 1) has an unusual molecular architecture and exhibits cytotoxic properties against the Hela and HEL cell lines (MIC: 6.25 and 3.13 μg mLÀ1, respectively).[1] Isolated from the gamboge resin of Garcina hamburyi in 1996, this naturally occurring substance provides an intriguing synthetic challenge and an opportunity for the development of new synthetic technology and biological tools. Herein we report a biomimetic [2] total synthesis of gambogin [3] and the observation of dramatic rate accelerations of the Claisen rearrangement and the Claisen/Diels–Alder cascade reaction [4] in protic solvents, most notably in water.Our retrosynthetic plan for the molecule of gambogin (1), whose resemblance to forbesione and lateriflorone [5] influenced our thinking, is shown in Scheme 1. Thus, applying a retro-Claisen rearrangement [6] on ring A (benzopyran ring, mixture of diastereomers) unraveled the acetylenic benzenoid compound 2, which could be derived from 3a through O-