Total synthesis of (+)-cortistatin A
Total synthesis of (+)-cortistatin A
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DOI：
10.1002/anie.200803550
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Chen, David Y-K.
中科院分区：
文献类型：
--
作者：
Nicolaou, K. C.;Sun, Ya-Ping;Chen, David Y-K.
血管生成是一种重要的生理现象，其失衡可能导致几种疾病状态，包括恶性、炎症、缺血性、感染性和免疫性疾病。[1]一段时间以来，血管生成的抑制被认为是改善这种状况的有吸引力的方法。随着近年来第一批抗血管生成药物的问世，寻找新的血管生成抑制剂成为当务之急。2006年[2]和2007年[3，4]，小林研究小组发现了一系列具有显著抗血管生成特性的甾体生物碱，这些甾体生物碱具有有效的抗增殖活性。从海绵Corticium simplex中分离出来，并命名为corticostatin，这些分子拥有一个七环骨架，具有氧杂双环-[3，2，1]辛烯和一些异喹啉结构基序。从皮质抑素家族的11个天然存在的成员中，皮质抑素A（1，方案1; IC 50 = 1.8 nm，
Angiogenesis is an important physiological phenomenon whose imbalance may result in several disease states, including malignant, inflammatory, ischaemic, infectious, and immune disorders.[1] The inhibition of angiogenesis has been considered for some time as an attractive way to improve such conditions. With the recent introduction of the first antiangiogenic agents to treat cancer and blindness, the search for new inhibitors of angiogenesis assumed a new level of priority and urgency.In 2006 [2] and 2007,[3, 4] the Kobayashi research group disclosed a series of novel steroidal alkaloids possessing remarkable anti-angiogenic properties that endow them with potent anti-proliferative activities. Isolated from the sponge Corticium simplex, and named cortistatins, these molecules boast a heptacyclic skeleton featuring an oxabicyclo-[3, 2, 1] octene and, some, an isoquinoline structural motif. From the 11 naturally occurring members of the cortistatin family, cortistatinA (1, Scheme1; IC50= 1.8 nm against