吲哚衍生物合成与应用的研究进展

综述了以苯胺衍生物(或硝基苯衍生物)为原料合成吲哚衍生物的方法和吲哚衍生物的应用。吲哚类化合物的合成方法主要有：Fischer合成法,苯胺衍生物合成法,硝基衍生物合成法和Nenitzescu合成法等。吲哚衍生物在制药、染料和香料等领域有重要应用。参考文献105篇。     

单萜吲哚生物碱的合成生物学研究进展

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.     

无过渡金属催化条件下合成3,3'-二吲哚甲烷衍生物的最新进展（英文）

3,3'-二吲哚甲烷类化合物是一类重要的吲哚生物碱,其结构单元广泛存在于天然产物、功能性材料以及合成药物分子中.因其具有多样的生物活性和功能,如抗氧化、抗炎症、抗血管生成、抗菌以及抗癌活性等,构筑3,3'-二吲哚甲烷类杂环化合物备受关注.传统的合成方法,尤其是对称结构的3,3'-二吲哚甲烷类化合物的合成主要在化学量的Br?nsted酸或Lewis酸存在下,吲哚衍生物与羰基化合物经傅-克反应缩合得到.而过渡金属的使用可引起化合物中金属残留以及环境污染.总结和探讨了从2010年至今3,3'-二吲哚甲烷类化合物的合成方法,尤其是对无过渡金属参与条件下,对称结构的3,3'-二吲哚甲烷类化合物以及非对称结构3,3'-二吲哚甲烷类化合物制备的最新进展以及相应的反应机理,旨在为该类化合物生物活性测试提供重要的理论依据和技术支持.     

对映纯吲(口朶)喹嗪的合成

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     

吲哚与硝基烯的Friedel-Crafts反应的研究进展

吲哚作为核心结构广泛存在于生物碱和药物中,吲哚衍生物在生物体的生理活动中起着重要的作用,其中吲哚和硝基烯的Friedel-Crafts是生成吲哚衍生物的重要方法.按照反应中催化剂种类的不同分为:(1)无催化剂,(2)离子液体催化剂,(3)金属盐催化剂,(4)配合物催化剂,(5)Br nsted酸催化剂,(6)有机小分子催化剂,(7)其他类型催化剂.对吲哚与硝基烯的Friedel-Crafts反应的情况进行了综述.     

基于龙胆苦苷的二吲哚甲烷类拟单萜吲哚生物碱类似物合成及其抗肿瘤、逆转紫杉醇耐药活性研究

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。     

聚吲哚及其衍生物的荧光光谱

在三氟化硼乙醚及其混合电解质中,吲哚及其衍生物阳极氧化可以获得高质量的聚吲哚及其衍生物膜:聚吲哚、聚(5-甲基吲哚)、聚(5-硝基吲哚)、聚(5-氰基吲哚)、聚(5-溴吲哚).它们可溶于DMSO和THF中.聚吲哚及其衍生物具有良好的荧光性质;单体的发射光谱与取代基有关,而聚合物的发射光谱几乎不受取代基的影响.电子离域程度增大,使得聚合物的激发和发射光谱红移,宽的分子量分布则会使聚合物的激发和发射光谱变宽.     

Fischer吲哚合成法的研究进展

吲哚及其衍生物具有某些生物活性, 其合成方法很多. 其中Fischer吲哚合成是最便捷和经济的合成方法, 应用最多. 对此法近十年来的合成工艺进行了综述和评价.     

Cu(OTf)_2和脯氨亚磺酰胺共同催化吲哚与N-磺酰醛亚胺的Friedel-Crafts反应

3-取代吲哚甲胺衍生物因其多种生物活性而备受关注.吲哚与N-磺酰醛亚胺的Friedel-Crafts反应是制备3-取代吲哚甲胺衍生物的主要方法,但反应中通常会伴随大量的双吲哚甲烷化合物的生成.应用Cu(OTf)_2和脯氨亚磺酰胺共同催化吲哚与N-磺酰醛亚胺的Friedel-Crafts反应,可以选择性地合成3-取代吲哚甲胺衍生物,产率为65%~93%.该方法具有底物适用性好、反应条件温和、操作简单等优点.     

Leuconolam-Leuconoxine-Mersicarpine系列单萜吲哚生物碱的全合成研究进展

Leuconolam-leuconoxine-mersicarpine生物碱是一类主要从夹竹桃科蕊木属植物中分离得到、相互之间具有生源关系的单萜吲哚生物碱,展现出丰富的结构复杂性和多样性.这类吲哚生物碱的大多数成员都具有抗炎症、抗肿瘤等显著的生物活性.综述了国内外有机合成化学家对该类天然产物的全合成研究进展.     

Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa

The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.     

单萜吲哚生物碱的仿生合成

单萜吲哚生物碱因其骨架和官能团的丰富变化,加上它们的生物活性,多年来 一直哟引着一代又一代的化学家对其进行结构和合成研究,它们的共同生物合成前 体strictosidine是由色胺和单萜苷secologanin缩合形成的。自从secologanin可 以大量得到以后,以它为原料沿着可能的生物合成路线合成天然生物碱即仿生合成 就成为一个重要的研究领域。它对于理解和阐释生物碱的生物合成过程,为提供天 然来源极少的生物碱供药理试验及对促进有机合成化学的发展等都是有重要意义。 这方面的研究也取得了许多重要进展,成功合成了一些重要的单萜吲哚生物碱,如 育亨宾类、钩藤碱、异钩藤碱、卡得宾、利血平类似物、喜树碱等。     

Kopsifolines A–F: a New Structural Class of Monoterpenoid Indole Alkaloids from Kopsia

Six new indole alkaloids, named kopsifolines A–F ( 1 – 6 ), with an unprecedented hexacyclic carbon skeleton, constituting a new structural group of monoterpenoid indole alkaloids, were obtained from the leaf extract of a Malayan Kopsia species, and their structures were established by spectroscopic analysis.     

Two new monoterpenoid indole alkaloids from Tabernaemontana divaricata

Two new monoterpenoid indole alkaloids, tabervarines A (1) and B (2), along with seven known monoterpenoid indole alkaloids, were isolated from the methanol extract of the twigs and leaves of Tabernaemontana divaricata. The structures including the absolute configurations of the new alkaloids were elucidated based on MS, NMR, and ECD calculation. The in vitro cytotoxic activities of the isolated alkaloids against several human cancer cell lines were also evaluated.     

Bioinspired Transformations Using Strictosidine Aglycones: Divergent Total Syntheses of Monoterpenoid Indole Alkaloids in the Early Stage of Biosynthesis

A series of bioinspired transformations that are applied to convert strictosidine aglycones into monoterpenoid indole alkaloids is reported. The highly reactive key intermediates, strictosidine aglycones, were prepared in situ by simple removal of a silyl protecting group from the silyl ether derivatives, and converted selectively via bioinspired transformations under substrate control into heteroyohimbine- and corynantheine-type, and akagerine and naucleaoral related alkaloids. Thus, concise, divergent total syntheses of 13 monoterpenoid indole alkaloids, (−)-cathenamine, (−)-tetrahydroalstonine, (+)-dihydrocorynantheine, (−)-corynantheidine, (−)-akagerine, (−)-dihydrocycloakagerine, (−)-naucleaoral B, (+)-naucleidinal, (−)-naucleofficines D and III, (−)-nauclefiline, and (−)-naucleamides A and E, were accomplished in fewer than 13 steps.     

云南蕊木茎中的抗炎吲哚生物碱

应用多种色谱和波谱学方法,从云南蕊木(Kopsia officinalis)茎中分离鉴定了27个单萜吲哚生物碱,包括7个新化合物kopsiofficines A～G和20个已知化合物.此外,建立脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症模型,通过测定IL-1β, PGE2和TNF-α炎症因子释放评价生物碱的抗炎活性.结果表明, kopsiofficines A (1), kopsiofficines B (2),kopsiofficines D(4),kopsiofficines F(6),kopsiofficines G(7), 12-methoxykopsine(11),kopsinoline(15),(-)-N-methoxy-carbonyl-11,12-methylenedioxykopsinaline(16),kopsinine(18)和kopsinic acid(20)表现出显著的抗炎活性,与阳性对照(地塞米松)基本相当.研究发现C-5位丙酮基取代的单萜吲哚生物碱的抗炎活性明显强于原型生物碱,推测丙酮基可能是抗炎活性的药效促进基团,研究结果为进一步的结构修饰...     

The Double‐Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis

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.     

Three New Monoterpenoid Indole Alkaloids from Ervatamia flabelliformis

The three new monoterpenoid indole alkaloids 1 – 3 were isolated from the stems of Ervatamia flabelliformis. The structures were elucidated on the basis of spectral analysis and chemical derivatization.     

Discovery of Natural Co-occurring Enantiomers of Monoterpenoid Indole Alkaloids

Two new pairs of monoterpenoid indole alkaloids (MIAs) enantiomers as well as their new congeners were isolated from stems of Tabernaemontana bovina Lour.(Apocy...     

Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium elegans benth

[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.