Stereochemical and Biochemical Mechanisms in Lignan Biosynthesis

在本研究开始之前，已有多篇关于连翘属植物木脂素生物合成的论文发表，并概述了其立体化学机制。另一方面，人们对其他植物中木脂素的生物合成知之甚少，特别是那些产生与连翘植物中木脂素相反的对映体的植物。本研究旨在阐明木脂素在多种植物中合成的立体化学机制。首先进行文献综述，总结了目前从各种植物中分离到的木脂素的旋光性标志。在数据分析的基础上，选择三种植物作为植物材料，探讨木脂素生物合成的立体化学机制：其次，从这些植物中分离出多种木脂素，手性高效液相色谱分析表明，其中许多木脂素与连翘属植物中的木脂素对映体相反，如从牛蒡中分离到与连翘属植物中（-）对映体相反的(+)-二异木脂树脂醇（78% e.e.e）。第三，从牛蒡中发现一种酶制剂可以催化非手性松柏醇对映选择性生成(+)-二异松柏树脂醇（20% e.e）。这是第一个酶促反应选择性地产生(+)-二异松脂醇对映体的例子。根据酶促反应和氘标记化合物投料实验的结果，建立了木脂素的生物合成途径。分析结果表明，不同的植物形成不同的对映体，并且在不同的植物中产生光纯木脂素的代谢步骤可能不同。综上所述，本研究揭示了连翘、牛蒡子和丁香属植物中木脂素合成的立体化学机制存在很大差异。少

Before the present investigation was started, several papers had been published on lignan biosynthesis in Forsythia plants, and outline of its stereochemical mechanisms was elucidated. On the other hand, little was known about lignan biosynthesis in other plants, especially those producing the lignans which are the opposite enantiomers to those occurring in Forsythia plants. The present investigation has dealt with elucidation of stereochemical mechanisms for lignan biosynthesis in various plants.First, literature survey was carried out to summarize sign of optical rotation of various lignans which were isolated so far from various plants. Based on the analysis of the data three plants were selected for plant materials to investigate stereochemical mechanisms in lignan biosynthesis in the present investigation : Arctium lappa, Wikstroemia sikokiana, and Phyllanthus sp. Second, various lignans were isolated from the plants, and chiral HPLC analysis showed that many of them are the oppos … More ite enantiomers to those occurring in Forsythia spp. For instance, (+) -secoisolariciresinol (78% e.e.) which is the opposite enantiomer to the (-) -antipode from Forsythia spp.was isolated from Arctium lappa. Third, an enzyme preparation from Arctium lappa was found to catalyze enantioselective formation of (+) -secoisolariciresinol (20% e.e.) from achiral coniferyl alcohol. This is the first example of an enzymatic reaction to produce (+) -secoisolariciresinol enantioselectively. Based on the results of the enzymatic reaction and feeding experiments with deuterium-labelled compounds biosynthetic pathways of the lignans were established.Analysis of the results indicated that different enantiomers are formed in different plants and that metabolic steps to produce the optically pure lignans are probably different in the plants. In conclusion, the present investigation revealed that there is a great diversity in stereochemical mechanisms for lignan biosynthesis in Forsythia, Arctium and Wikstroemia plants. Less