Biomimetically inspired total synthesis and structure activity relationships of 1-O-methyllateriflorone.: 6π electrocyclizations in organic synthesis
Biomimetically inspired total synthesis and structure activity relationships of 1-O-methyllateriflorone.: 6π electrocyclizations in organic synthesis
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DOI：
10.1021/ja040037
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发表时间：
2004-05-05
影响因子：
15
通讯作者：
Xu, H
中科院分区：
文献类型：
--
作者：
Nicolaou, KC;Sasmal, PK;Xu, H
报道了1- o -甲基红芴酮(2)的全合成。该分子的笼状结构域的构建涉及仿生Claisen/Diels-Alder级联，而新的螺胞嘧啶-内酯框架是由前体16a内的分子内Michael反应产生的，羧酸残基作为亲核试剂。这一发现可能与自然界形成红叶红花的生物合成途径有关。本文还描述了一个有趣的级联序列，涉及容易的6t电环化，导致复杂的苯并吡喃系统。本文还包括了一个小文库的红叶花酮类似物和相关系统的生物学评价，这些系统在这类化合物中建立了第一个SAR。对肿瘤细胞最有效的化合物有2,16b, 56, 58和59。
The total synthesis of 1-O-methyllateriflorone (2) is described. The construction of the cage-like domain of the molecule involved a biomimetic Claisen/Diels-Alder cascade, whereas the novel spiroxa-lactone framework was generated by an intramolecular Michael reaction within precursor 16a involving the carboxylate residue as the nucleophile. This finding might bear on the biosynthetic pathway by which nature forms lateriflorone. Described herein is also an interesting cascade sequence involving facile 6 T electrocyclizations which leads to complex benzopyran systems. The biological evaluation of a small library of lateriflorone analogues and related systems establishing the first SAR within this class of compounds is also included. Among the most active compounds against tumor cells are 2, 16b, 56, 58, and 59.