海洋二聚吡咯-咪唑类生物碱

近20年来,大量二聚吡咯-咪唑类生物碱从海绵中分离得到,并表现出良好的生理活性。而这些分离上的进展,为确定该类化合物结构提供新的信息,更促进了生源合成的研究发展。这类化合物因其结构新颖性、多样性以及良好的生理活性而成为合成化学家们关注的焦点。由于该类天然产物分子结构的复杂性、分子中的高氮数(N/C ≈ 1 ∶2)以及不确定的绝对构型,使得这类分子的合成十分具有挑战性。本文主要综述了海洋二聚吡咯-咪唑类生物碱的分离和合成进展。     

吲哚生物碱Alsmaphorazine D的全合成

<正>Angew.Chem.Int.Ed.2015,54,879~882夹竹桃科鸡骨常山属植物广泛存在于非洲和亚洲的热带地区,目前已成为熟知的富含独特单萜吲哚骨架结构的杂环生物碱的主要来源.此类生物碱由于其生源合成途径的有趣性以及抗肿瘤、抗菌、抗炎、止咳和抗疟疾等显著的生理活性引起了化学家们很大的研究兴趣.最近,日本星药科大学药学系Morita课题组从生长于马来西亚的鸡骨常山属植物的呼吸根叶的提取物中分离得到了一类新的生物碱结构,并将其命名为Alsmaphorazines A~E.在此家族中,Alsmaphorazines D和E具有一种新颖的六氢吡咯[2,3-b]吡咯并二氮杂双环[3.3.1]壬烷核心结构,并且分子中含     

抗肿瘤生物碱Lamellarin N和Lamellarin L的研究进展

Lamellarins是一类从海洋无脊椎动物中分离的具有生物活性的吡咯生物碱,其中Lamellarin N(LMN)是Lamenllarin类化合物中的一员.LMN对一系列肿瘤细胞具有很高的细胞毒性,抑制蛋白激酶等活性,与具有强生物活性的Lamellarin D(LMD)相比更胜一筹.由于Lamellarin L(LML)结构和活性与LMN非常相似,因此对其提取分离、合成、生物活性及抗肿瘤细胞机理进行了综述.     

吡咯并二氢吲哚(+)-Flustramine B的立体选择性合成

吡咯并二氢吲哚和二吡咯并二氢吲哚代表着一类结构复杂的聚二氢吲哚生物碱,它们广泛存在于植物、海藻和两栖动物中[1].这类生物碱具有显著的生物活性,例如,从霉菌源分离出的( )-Flustramine B是缩胆囊肽和神经激肽受体的有力抗体[2].目前仅有Flustramine B的两个合成被报道,且两个都是外消旋形式[3].这里,我们将通过有机催化的吡咯并二氢吲哚的合成技术,一步对应选择性地合成Flustramine的溴-三环系统.     

植物内生真菌生物碱活性成分的研究进展

大量的生物碱从植物内生真菌中分离了出来, 并表现出良好的生物活性. 对植物内生真菌所产生的生物碱, 按照酰胺类、有机胺类、吡咯类、喹啉和异喹啉类、吲哚类、吡啶类、喹唑啉类进行了综述, 并且介绍了这些生物碱的生物活性.     

3,4-二芳基吡咯酮衍生物的合成和生物活性

考布他汀-A4(Combretastatins-A4,CA-4)是从天然产物中分离得到的抗癌活性化合物,其分子中Z-构型烯键易异构化转变为无抗癌活性的E-构型.以吡咯-2,5-二酮或吡咯-2-酮代替烯键,设计合成了4个新的CA-4类似物.它们的合成是以3,4-二甲氧基苯乙酮或3-氟-4-甲氧基苯乙酮为起始原料,经α-溴化、改良的Gabriel合成法、与3,4,5-三甲氧基苯乙酸缩合、环化-氧化或环化四步反应完成.其结构用1H NMR,13C NMR,ESI-MS及元素分析进行了表征.用MTT法测试了CA-4类似物对人白血病细胞HL-60、肝癌细胞SMMC-7721和肺腺癌细胞A549的体外抗肿瘤活性.初步结果表明,含氟化合物3,4-二芳基-2,5-吡咯酮(1b)的抗肿瘤活性接近CA-4,IC50值达到0.03～0.05μmol·L-1.     

2-乙氧羰基-3-溴-4-甲基-5-甲酰基-吡咯的合成

2-乙氧羰基-3-溴-4-甲基-5-甲酰基-吡咯的合成;乙氧羰基二甲基吡咯;乙氧羰基溴二甲基吡咯;乙氧羰基溴甲基甲酰基吡咯     

一锅法合成开链片螺素-吡咯异喹啉羧酸乙酯

片螺素(Lamellarins)是一类从海洋软体动物中提取的具有良好生物活性的吡咯类生物碱.自1985年,Faulkner等首次从前腮亚纲软体动物中提取出片螺素A-D[1]后,国内外便开始对各类片螺素及其衍生物的全合成进行研究,至今相关合成报道络绎不绝[2][3].与此同时多种开链片螺素也是一类具有特殊生物活性的吡咯类生物碱,由于目前还未有关其提取的报道,因此对其进行合成具有重要意义.     

吲哚类生物碱的合成研究进展

吲哚类生物碱是具有吲哚分子骨架的一类化合物,具有多种良好的生理活性。文章综述了近年来新发现吲哚类生物碱的合成研究进展,介绍了(-)-Arboricine,(±)-cis-Trikentrin A,(-)-Corynantheidol等化合物的合成方法。     

金鸡纳碱衍生物催化的异氰酸酯与硝基烯的不对称形式[3＋2]环化反应

手性2,3-二氢吡咯是合成天然生物碱的重要中间体，而且可以很容易转化成多取代的吡咯烷，因此发展高效合成手性二氢吡咯的方法对于有机合成化学具有重要意义．不对称诱导和金属催化合成光学活性的吡咯烷的方法已有很多，但还没有不对称催化合成手性2,3-二氢吡咯的报道．金属化的异氰与不饱和烯烃可以环化生成消旋的二氢吡咯（Saegusa，T；Ito，Y．；Kinoshita，H．；Tomita，S．，Org．Chem．1971，36，3316），     

Dispacamide E and other bioactive bromopyrrole alkaloids from two Indonesian marine sponges of the genus Stylissa

Chemical investigation of methanolic extracts of the two Indonesian marine sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrrole alkaloids including 2 new metabolites. The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR, LR-MS and HR-MS analyses. All isolated compounds were assayed for their antiproliferative and protein kinase inhibitory activities. Several of the tested compounds revealed selective activity(ies) which suggested preliminary SARs of the isolated bromopyrrole alkaloids.     

Nagelamides K and L, dimeric bromopyrrole alkaloids from sponge Agelas species

Two new dimeric bromopyrrole alkaloids, nagelamides K (1) and L (2), have been isolated from Okinawan marine sponges Agelas species, and the structures and stereochemistry were elucidated from spectroscopic data. Nagelamide K (1) is a bromopyrrole alkaloid possessing a rare piperidinoiminoimidazolone ring with an aminoimidazole ring and a taurine unit, while nagelamide L (2) is a unique dimeric bromopyrrole alkaloid containing an ester linkage. Nagelamides K (1) and L (2) exhibited antimicrobial activity.     

Agesamides A and B, bromopyrrole alkaloids from sponge Agelas species: application of DOSY for chemical screening of new metabolites

Diffusion-ordered NMR spectroscopy (DOSY) is a versatile and powerful NMR technique and a noninvasive analytical method for mixture analysis that does not require prior physical separation of the analytes. In our search for new metabolites from natural resources, DOSY was applied for constituent analysis of crude bromopyrrole fractions separated from an Okinawan marine sponge Agelas sp. so that two new bromopyrrole alkaloids, agesamides A (1) and B (2), have been isolated. The structures and relative stereochemistry of 1 and 2 were elucidated from spectroscopic data.     

Syntheses of manzacidins: a stage for the demonstration of synthetic methodologies

Manzacidins, a family of bromopyrrole alkaloids, have attracted much attention from the synthetic community due to their intriguing structures, bearing chiral tertiary and secondary stereocentres in a 1,3-relationship, and biological activities. In this article, we summarise the approaches for the preparation of manzacidins using novel synthetic methodologies. Organocatalysis and Lewis acid catalysis, as well as transition-metal catalysis, offered efficient ways to access these molecules.     

Nagelamides M and N, new bromopyrrole alkaloids from sponge Agelas species

Two new bromopyrrole alkaloids, nagelamides M (1) and N (2), have been isolated from an Okinawan marine sponge Agelas species, and the structures and stereochemistry were elucidated from the spectroscopic data. Nagelamide M (1) is a novel bromopyrrole alkaloid possessing a 2-amino-octahydropyrrolo[2,3-d]imidazole ring with a taurine unit, while nagelamide N (2) is a new bromopyrrole alkaloid possessing a 2-amino-tetrahydroimidazole-4-one ring with a taurine unit and 3-(dibromopyrrole-2-carboxamido)propanoic acid moiety. Nagelamides M (1) and N (2) exhibited antimicrobial activity.     

Nagelamide J, a novel dimeric bromopyrrole alkaloid from a sponge Agelas species

A novel dimeric bromopyrrole alkaloid, nagelamide J (1), with antimicrobial activity has been isolated from an Okinawan marine sponge Agelas species, and the structure and stereochemistry were elucidated from spectroscopic data. Nagelamide J (1) is the first bromopyrrole alkaloid possessing a cyclopentane ring fused to an amino imidazole ring.     

Misenine,a Novel Macrocyclic Alkaloid with an Unusual Skeleton from the Mediterranean Sponge Reniera sp

PolycycJic marine alkaloids containing 3-alkylpyridine or partially reduced 3-alkylpyridine as basic building blocks represent an emerging and intriguing group of bioactive natural products from marine sponges. Since halitoxin,² the first example of this kind of alkaloid, was reported in 1978, many related alkaloids have been discovered from sponges of the order Haplosclerida. All of these alkaloids, in spite of formally exhibiting quite different frameworks, could biogeneticaliy derive from bis-3-alkylpyridine or reduced bis-3-alkylpyridine units. In the last decade, the knowledge of this fascinating group of compounds has increased remarkably. A recent review has exhaustively studied occurrence, distribution, plausible biogenetic origin and relatedness, as well as biological activities, of 3-alkylpyridine derived marine alkaloids.³     

Organocatalytic enantioselective formal synthesis of bromopyrrole alkaloids via aza-Michael addition

An unprecedented organocatalytic enantioselective formal synthesis of bromopyrrole alkaloid natural products is reported. An organocatalytic aza-Michael addition using pyrroles as the N-centered nucleophile is utilized as the enantioselective step to construct the nitrogen-substituted stereogenic carbon center in bromopyrrole alkaloids in good yield and excellent enantioselectivity. The aza-Michael product is converted via lactamization using a Staudinger-type reductive cyclization to the key intermediate, which was previously used in the total synthesis of bromopyrrole alkaloid natural products.     

A journey under the sea: the quest for marine anti-cancer alkaloids

The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many are now being tested in various phases of clinical trials. Recently, marine-derived alkaloids, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to also exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and tubulin polymerization, and induction of apoptosis and cytotoxicity. Two tunicate-derived alkaloids, aplidin and trabectedin, offer promising drug profiles, and are currently in phase II clinical trials against several solid and hematologic tumors. This review sheds light on the rich array of anti-cancer alkaloids in the marine ecosystem and introduces the most investigated compounds and their mechanisms of action.