Synthesis of the proposed structure of mucoxin via regio- and stereoselective tetrahydrofuran ring-forming strategies
Synthesis of the proposed structure of mucoxin via regio- and stereoselective tetrahydrofuran ring-forming strategies
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DOI：
10.1021/jo052073c
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发表时间：
2006-02-17
影响因子：
3.6
通讯作者：
Borhan, B
中科院分区：
文献类型：
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作者：
Narayan, RS;Borhan, B
描述了所提出的粘蛋白 (1) 结构的对映选择性全合成。 Mucoxin 是一种从 Rollinia 粘膜生物活性叶提取物中分离出来的番荔枝苷元，是第一个含有羟基化三取代四氢呋喃 (THF) 环的乙酰苷元。该天然产物是一种针对MCF-7（乳腺癌）细胞系的高效且特异性的抗肿瘤剂（与阿霉素相比，ED50 = 3.7 x 10(-3) mu g/mL，ED50 = 1.0 x 10(-2) mu g/mL）。本文描述的全合成以两个区域选择性和立体选择性THF成环反应为特征。使用亚甲基中断的环氧二醇的高度区域选择性环化获得2,3,5-三取代的THF部分(C13-C17)，并通过1,2-n-三醇环化策略方便地组装2,5-二取代的THF环(C8-C12)。合成材料及其两种非对映异构体的光谱数据与天然产物的报告数据不匹配。在对合成分子进行详细光谱分析的基础上，我们推断光谱差异是由于天然产物的立体化学错误分配造成的。
An enantioselective total synthesis of the proposed structure of mucoxin (1) is described. Mucoxin, an annonaceous acetogenin isolated from bioactive leaf extracts of Rollinia mucosa, is the first acetogenin containing a hydroxylated trisubstituted tetrahydrofuran (THF) ring. This natural product is a highly potent and specific antitumor agent against MCF-7 (breast carcinoma) cell lines (ED50 = 3.7 x 10(-3) mu g/mL compared to adriamycin, ED50 = 1.0 x 10(-2) mu g/mL). The total synthesis described herein features two regio- and stereoselective THF ring-forming reactions. The 2,3,5-trisubstituted THF portion (C13-C17) was accessed using a highly regioselective cyclization of a methylene-interrupted epoxydiol, and the 2,5-disubstituted THF ring (C8-C12) was conveniently assembled via a 1,2-n-triol cyclization strategy. The spectral data of the synthetic material and two of its diastereomers did not match the reported data for the natural product. On the basis of detailed spectroscopic analysis of the synthesized molecule, we reason that the spectral discrepancies are due to stereochemical misassignment of the natural product.