Eckermann Ruben, Gaich Tanja
Institute of Organic Chemistry, Leibniz University of Hannover, Schneiderberg 1b, 30167, Hannover, Germany.
Department of Organic Chemistry, University of Konstanz, Universitätsstrasse 10, 78464, Konstanz, Germany.
Chemistry. 2016 Apr 11;22(16):5749-55. doi: 10.1002/chem.201505068. Epub 2016 Mar 2.
Experimental evidence is provided for the coherence of the double-bond geometry and the occurrence of "secondary cyclizations" in the biosynthesis of monoterpenoid indole alkaloids. Biosynthetically, akuammiline, C-mavacurine, and Strychnos alkaloids are proposed to be derived from the corynanthean alkaloid geissoschizine, a key intermediate in the biosynthetic pathway of these monoterpenoid indole alkaloids. This process occurs by so-called "secondary cyclizations" from geissoschizine or its derivatives. Although corynanthean alkaloids like geissoschizine incorporate E or Z double bonds located at C19-C20, the alkaloids downstream in the biosynthesis exclusively exhibit the E double bond. This study shows that secondary cyclizations preferentially occur with the E isomer of geissoschizine or its derivatives. This is attributed to the flexibility of the quinolizidine system of the corynanthean alkaloids, which can adopt a cis or trans conformation. For the secondary cyclization to take place, the cis-quinolizidine conformation is required. Experimental evidence supports the hypothesis that the E double bond of geissoschizine induces the cis conformation, whereas the Z double bond induces the trans conformation, which prohibits secondary cyclization of the Z compounds.
实验证据表明，在单萜吲哚生物碱的生物合成中，双键几何结构具有连贯性，且存在“二级环化”现象。从生物合成角度来看，阿枯米灵、C-马瓦库林和马钱子属生物碱被认为源自可利那生生物碱基索希嗪，它是这些单萜吲哚生物碱生物合成途径中的关键中间体。这个过程通过基索希嗪或其衍生物的所谓“二级环化”发生。尽管像基索希嗪这样的可利那生生物碱在C19 - C20位含有E型或Z型双键，但生物合成下游的生物碱仅呈现E型双键。本研究表明，二级环化优先发生在基索希嗪或其衍生物的E型异构体上。这归因于可利那生生物碱喹诺里西啶系统的灵活性，它可以采取顺式或反式构象。为了发生二级环化，需要顺式喹诺里西啶构象。实验证据支持这样的假设，即基索希嗪的E型双键诱导顺式构象，而Z型双键诱导反式构象，这阻止了Z型化合物的二级环化。
