Studies on the biosynthesis of paraherquamide A and VM99955.: A theoretical study of intramolecular Diels-Alder cycloaddition
Studies on the biosynthesis of paraherquamide A and VM99955.: A theoretical study of intramolecular Diels-Alder cycloaddition
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DOI：
10.1021/jo020564g
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发表时间：
2003-04-04
影响因子：
3.6
通讯作者：
Williams, RM
中科院分区：
文献类型：
--
作者：
Domingo, LR;Zaragozá, RJ;Williams, RM
在B3LYP/6-31G*水平上对2-氮二烯模型的分子内Diels-Alder反应进行了量子化学研究，以阐明生物合成对苯二胺A和VM99955的环化步骤的立体化学特征。这些环加成反应通过与[4+2]过程相关的协同过渡态进行。沿竞争路径的能量分析表明，当氧吲哚的环加成反应表现出很大的反选择性时，吲哚对形成C20立体中心表现出较低的同步选择性，而对于还原的叔胺形式来说，该选择性较大。β-甲基脯氨酸环的C14甲基的存在对异戊二烯骨架的SYN方法产生了沿反应坐标的低阻碍，这与实验发现的低表面选择性一致。对分子间和分子内Diels-Alder反应实验模型的亲电性和活化参数的分析揭示了控制这些生物合成环化反应的几个重要因素。计算结果与已有的实验数据吻合较好。
Intramolecular Diels-Alder reactions of 2-azadiene models have been studied quantum chemically at the B3LYP/6-31G* level in order to elucidate the stereochemical features of the cyclization step involved in the biosynthesis of paraherquamide A and VM99955. These cycloadditions take place through concerted transition states associated with [4 + 2] processes. Analysis of the energies along the competitive paths reveals that while the cycloadditions of the oxindoles present a large anti selectivity, the indoles show a low syn selectivity for the formation of the C20 stereogenic center that is larger for the reduced tertiary amide form. The presence of the C14 methyl of the beta-methylproline ring produces a low hindrance along the reaction coordinate for the syn approach of the isoprene framework, in agreement with the low facial selectivity found experimentally. An analysis of the electrophilicity and activation parameters for experimental models of the inter- and intramolecular Diels-Alder reactions reveals several significant factors controlling these biosynthetic cyclizations. The results are in reasonable agreement with the available experimental data.