共查询到18条相似文献,搜索用时 171 毫秒
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单萜吲哚生物碱是一类具有重要药用价值的天然产物,但是在其宿主的生物含量很低;虽然通过有机化学的方法可以实现该类复杂结构化合物的全合成,但是难以大量快速获得,而且围绕核心骨架的进一步衍生化修饰也有一定的瓶颈.随着单萜吲哚生物碱生物合成途径的解析和合成生物学使能技术的发展,利用合成生物学策略结合化学半合成将是实现该类化合物的合成制造和通量结构衍生化的重要发展趋势.单萜吲哚生物碱基因元件的挖掘鉴定和生物合成途径的解析是进行合成生物学研究的前提条件.异胡豆苷是单萜吲哚生物碱合成的关键骨架化合物,由色胺和开环马钱子苷汇聚合成,这一过程被称为上游合成途径;以异胡豆苷为骨架形成各种单萜吲哚生物碱的过程称为下游合成途径.从这两个方面对近30年来单萜吲哚生物碱合成元件的发现和合成生物学研究进展进行了综述,为后续合成生物学的应用研究奠定基础. 相似文献
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喜树碱是从中国植物喜树(Camptotheca acuminata)中分离得到的抗癌生物碱 ,由于其独特的抗癌机理而成为抗癌药研究中的热门课题.喜树碱属于单萜吲哚生 物碱类,由色胺和secologanin缩合、衍生而来.它的仿生合成始于1972年,先后 有多人参加,直到1997年在经历了四分之一世纪之后才取得了成功.介绍喜树碱仿 生合成背后鲜为人知的故事. 相似文献
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以环烯醚萜类化合物龙胆苦苷为合成模块,利用拟单萜吲哚生物碱的仿生合成途径和组合化学的研究思路,与色胺类衍生物(吲哚结构的活性单元片段)通过缩合反应,首次合成了23个二吲哚甲烷类拟单萜吲哚生物碱类似物。利用核磁共振波谱(NMR)和高分辨质谱(HRMS)等谱学手段对合成化合物的结构进行了表征,并初步评价了其抗肿瘤活性和逆转耐药活性。活性结果表明,化合物4i脱掉糖基保护基后的化合物5i对3种肿瘤细胞系(TE-1,CAL-62和FaDu)的抑制作用强于阳性对照盐酸阿霉素(Dox)。通过与紫杉醇的联合用药,发现部分化合物如4m、4n、4o、4r等能够有效降低人肺癌细胞紫杉醇耐药株A549/Taxol对紫杉醇的耐药性,具有良好的逆转耐药潜力。 相似文献
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育亨宾类(Yohimbimes)和杂育亨宾类(Heteroyohimbines)如利血平(Reserpine,1)、阿吗新(Ajmalicine)等是具有重要心脑血管活性的天然吲哚生物碱。1980年 Roycr 和Lévy 在研究吲哚生物碱合成中偶然发现3α-杂育亨宾生物碱四叶萝芙灵(Tetraphylline,2)在先用氰基硼氢化钠和三氟醋酸,后用40%甲醛和氰基硼氢化钠处埋后,可直接一步得到2β,3α,7β-cis(B/C)-trans(C/D)的1,10-二甲基-2,7-二氢四叶萝芙灵(3a)。以后,此 相似文献
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3-乙酰基-1,4,6,7,12,12b-六氢吲哚[2,3-a]喹嗪(15,16)是吲哚生物碱及羟吲哚生物全合成中用途极广的通用建筑块。合成对映纯的15和16,一直是吲哚生物碱及羟吲哚生物碱全合成中的重要课题。Winterfeldt 首先报道了外消旋体15/16的合成及它与丙二酸二甲酯的高度立体选择性加成。为了改进阿马里新的全合成,Mandal 等1985年再次研究了 相似文献
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Alstonerine属于单萜吲哚生物碱,除其结构很有特征外,还报道对两株人肺癌细胞具有细胞毒性,因此,它自然就成为合成化学的重要目标.已经有多种合成策略用于构建这个结构体系:包括Pictet-Spengler反应和Dieckmann缩合反应、烯烃复分解关环反应、膦配体催化的[4+2]关环/Friedel-Craft环化、氮杂-Diels-Alder反应/分子内Heck反应、Pauson-Khand反应等.本工作根据构建环系的不同反应系统总结了Alstonerine的合成方法.大部分合成反应步骤较多,适合工业生产的有效合成方法还有待于进一步探索. 相似文献
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Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries 总被引:2,自引:0,他引:2
Loris EA Panjikar S Ruppert M Barleben L Unger M Schübel H Stöckigt J 《Chemistry & biology》2007,14(9):979-985
The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented. 相似文献
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Lutz-F. Tietze 《Angewandte Chemie (International ed. in English)》1983,22(11):828-841
The monoterpene glycoside secologanin is a key intermediate in the biosynthesis of most indole, cinchona, ipecacuanha, and pyrroloquinoline alkaloids, as well as of simple monoterpene alkaloids. More than a thousand alkaloids are formed from secologanin in vivo; this represents almost a quarter of this large group of natural products. It is also the parent compound of the secoiridoids. Many of the compounds derived from secologanin display a high degree of biological activity and are employed as pharmaceuticals, e.g., the dimeric indole alkaloid leurocristine (vincristine) which is used very successfully in the treatment of acute leukemia. A knowledge of the biosynthesis and biological reactions of secologanin provides a sound basis for the biosynthesis-orientated classification of numerous natural products and the taxonomy of many plants. Secologanin and structurally related substances can be synthesized in a few steps by stereocontrolled photochemical and thermal cycloadditions. Its biomimetic reaction with amines and amino acids yields other natural products and compounds of pharmacological interest. 相似文献
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As part of a general project on the chemistry of alkaloid analogues, the synthesis of derivatives 5 , of 4,5,6,6a,7,12-hexahydroisoquinolino[8,l-ab]carbazole, which can be considered as ring D indole analogues of the aporphine skeleton, was investigated. Compounds of this type are of interest on two grounds. Firstly it is conceivable some may occur naturally; and secondly, they may display unusual pharmacological properties, since the side-chain configuration of the tryptophan residue is intermediate between that present in lysergic acid diethylamide and the yohimbine-reserpine type alkaloids. 相似文献
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The Double‐Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis 下载免费PDF全文
Ruben Eckermann Prof. Dr. Tanja Gaich 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(16):5749-5755
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. 相似文献
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Jukiya Sakamoto Yuhei Umeda Kenta Rakumitsu Prof. Dr. Michinori Sumimoto Prof. Dr. Hayato Ishikawa 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(32):13516-13524
A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α-cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)-strictosidine, which is an important intermediate in biosynthesis. This two-step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)-strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)-strictosamide, (−)-neonaucleoside A, (−)-cymoside, and (−)-3α-dihydrocadambine. 相似文献
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[reaction: see text] New types of four gelsenicine-related oxindole alkaloids were isolated from the leaves of Gelsemium elegans Benth. Gelsedilam (1) and 14-acetoxygelsedilam (2) are the first examples of 18,19-nor-type monoterpenoid indole alkaloids. Gelsefuranidine (3) and gelseiridone (4) have, respectively, an additional furan residue or an iridoid unit on the gelsenicine-related monoterpenoid indole alkaloid. 相似文献
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Two new oxindole alkaloids, rankiniridine (1) and humanteniridine (2), having a nitrogen-carbon linkage between a humantenine-type monoterpenoid indole alkaloid and a monoterpene unit with an iridoid skeleton, were isolated from Gelsemium rankinii and Gelsemium elegans, respectively. 相似文献
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Yousuke Yamada 《Tetrahedron》2008,64(33):7690-7694
Four new gelsedine-type oxindole alkaloids (1-4) were isolated from the leaves and branches of Gelsemium elegans, together with 10 known alkaloids. The structures of the new alkaloids were determined by spectroscopic analyses and partial synthesis from known compounds. Gelsecrotonidine (1), 14-hydroxygelsecrotonidine (2), and 11-methoxygelsecrotonidine (3) possess an additional C2 unit with an acetic acid residue compared to gelsenicine-related monoterpenoid indole alkaloids. 14-Hydroxygelsedilam (4) is an 18,19-nor-type monoterpenoid indole alkaloid. 相似文献