7-取代吲哚类化合物合成及官能团化研究进展

7-取代吲哚化合物是合成药物及精细化学品的重要中间体.本文综述了近15年金属Pd催化的7-取代吲哚化合物的制备方法,将其分成直接合成法和吲哚7位官能团化法两类,对每一类的反应过程和机理进行了详细介绍和评述.     

竹红菌甲素和吲哚类化合物的相互作用

本文利用吸收光谱,荧光光谱研究了竹红菌甲素(以下简称HA)和吲哚类化合物的相互作用。发现HA和吲哚类化合物在一定条件下可形成复合物。这种复合物带有电荷转移性质。吲哚环上带有给电子取代基,位阻小,溶剂的极性大和溶液呈中性有利于该复合物的形成。     

用2-甲基吲哚作偶合剂测定克仑特罗片

试验了用2-甲基吲哚测定克仑特罗片的新方法。克仑特罗在酸性溶液中被亚硝酸钠重氮化后,能与2-甲基吲哚偶合成黄色化合物,该化合物的最大吸收波长λmax389nm,摩尔吸光系数ε为2.36×104L.mol-1.cm-1,该法线性范围0~24mg/L,最低检测限为0.14mg/L,有色化合物至少稳定2h,此法适用于药品生产中的质量监控。     

酶法合成中色氨酸的测定

建立了光度测定酶法合成中色氨酸含量的新体系。该检测体系不仅能准确地测定产物色氨酸的含量，且对底物吲哚能同时测定。有效地避免了其他色氨酸测定方法底物吲哚的干扰，通过标准加入法色氨酸及吲哚的回收率分别为９７．８％～１０３．３％，９７．６％～１０３％。实验证明该体系简单、实用，测定结果可靠。     

5，11-二乙基吲哚[3，2-b]咔唑的合成及光谱特性

以苯肼为原料,与1,4-环己二酮反应,制得环己胺-1,4-二酮一二苯腙,再在硫酸、醋酸强酸性环境下闭环制得吲哚[3,2-b]咔唑,经N-烷基化反应制得乙基取代基的吲哚[3,2-b]咔唑衍生物．本文合成方法使其产率由参考文献的64％提升到80％,其结构经’HNMR表征,并初步研究了该化合物的光谱性质．     

从甲基萘油中萃取吲哚的研究

用溶剂萃取法从甲基萘油中萃取吲哚.主要研究了不同溶剂、溶剂比、萃取温度、萃取时间和萃取级数对BO3和DMNO的吲哚萃取率的影响,结果表明,两种甲基萘油均采用正庚烷-三甘醇作萃取剂效果较好,BO3:三甘醇:正庚烷=1:1:2、DMNO:三甘醇:正庚烷=2:1:2为佳,萃取温度为30～40℃时较好,萃取理论级数取N=10比较适合,但萃取时间对BO3、DMNO的吲哚萃取率的影响较小.在对常规的双溶剂萃取研究的基础上,提出了吲哚加盐萃取方法.结果表明,在吲哚萃取过程中加入NaSCN和CH3COOK,不但能降低非极性物质在极性溶剂中的溶解度,提高吲哚的萃取选择性,而且还能够提高吲哚的萃取率.     

Gene Discovery in Gelsemium Highlights Conserved Gene Clusters in Monoterpene Indole Alkaloid Biosynthesis

Genome mining is a routine technique in microbes for discovering biosynthetic pathways. In plants, however, genomic information is not commonly used to identify novel biosynthesis genes. Here, we present the genome of the medicinal plant and oxindole monoterpene indole alkaloid (MIA) producer Gelsemium sempervirens (Gelsemiaceae). A gene cluster from Catharanthus roseus, which is utilized at least six enzymatic steps downstream from the last common intermediate shared between the two plant alkaloid types, is found in G. sempervirens, although the corresponding enzymes act on entirely different substrates. This study provides insights into the common genomic context of MIA pathways and is an important milestone in the further elucidation of the Gelsemium oxindole alkaloid pathway.     

Expanding the Diversity of Plant Monoterpenoid Indole Alkaloids Employing Human Cytochrome P450 3A4

Human drug-metabolizing cytochrome P450 monooxygenases (CYPs) have enormous substrate promiscuity; this makes them promising tools for the expansion of natural product diversity. Here, we used CYP3A4 for the targeted diversification of a plant biosynthetic route leading to monoterpenoid indole alkaloids. In silico, in vitro and in planta studies proved that CYP3A4 was able to convert the indole alkaloid vinorine into vomilenine, the former being one of the central intermediates in the ajmaline pathway in the medicinal plant Rauvolfia serpentina (L.) Benth. ex Kurz. However, to a much larger extent, the investigated conversion yielded vinorine (19R,20R)-epoxide, a new metabolite with an epoxide functional group that is rare for indole alkaloids. The described work represents a successful example of combinatorial biosynthesis towards an increase in biodiversity of natural metabolites. Moreover, characterisation of the products of the in vitro and in planta transformation of potential pharmaceuticals with human CYPs might be indicative of the route of their conversion in the human organism.     

色氨酸酶重组基因表达及其酶法合成L-色氨酸

为实现色氨酸酶高效、低成本催化合成L-色氨酸,利用p ET30a为载体在宿主细胞E.coli BL21(DE3)中重组表达了产气肠杆菌(Enterobacter aerogenes)来源的色氨酸酶,以丙酮酸、吲哚和氨为底物,探究其酶学性质,考察了反应温度、起始p H、底物摩尔比对酶促反应的影响,并利用丙酮酸发酵液为底物酶法合成L-色氨酸。结果表明,色氨酸酶重组表达成功,色氨酸酶最佳反应条件为:温度35℃,起始p H=9.0,底物摩尔比n(吲哚)∶n(丙酮酸)=0.6∶1,底物丙酮酸浓度为0.17 mol/L。利用重组色氨酸酶全细胞催化100 m L浓度为0.57 mol/L丙酮酸发酵液,流加浓度为4.27 mol/L吲哚酒精溶液6.5 m L,反应28 h后,L-色氨酸浓度达0.25 mol/L,吲哚摩尔转化率达91.8%。