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.     

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.     

片螺素中间体——2,4,5-三甲氧基-α-卤代苯乙酮的合成研究

片螺素[1](Lamel larin)及其类似生物碱是近年来自海洋生物中分离得到的一种海洋活性物质,迄今为止发现有39种[1][2]。所有的片螺素都具有一定的生物活性[3]。但由于海洋生物中片螺素具有含量低,分离困难等特点,因而其合成研究是十分有意义的。本课题组在国家自然基金资助下,设     

海洋软体动物活性物质——片螺素(lamellarin)及其类似生物碱的研究进展<

综述了海洋软体动物活性物质片螺素及其类生物碱的提取、分离、结构确定以及合成路线的研究进展, 并简要介绍了该类物质的生物活性.     

过渡金属催化合成吡咯-2-甲酸酯的研究进展

吡咯-2-甲酸酯广泛存在于生物活性分子中,在医药领域具有十分重要的应用,因此吡咯-2-甲酸酯类化合物的合成研究受到了广泛关注.过渡金属催化的环加成反应在合成吡咯骨架方面应用广泛,具有区域选择性专一的优点.且过渡金属配体导向的C-N键构筑方法具有原子步骤经济性较高、效率高、反应条件温和以及选择性高等优点.按照过渡金属催化剂分类,对吡咯-2-甲酸酯的[3+2]、[4+1]与[2+2+1]等成环反应的合成方法进行综述,介绍了过渡金属催化吡咯-2-甲酸酯化合物的机理及其应用,并对吡咯-2-甲酸酯的合成进行了展望.     

2H-吡咯的简易合成方法:金催化与路易斯酸催化的组合应用

报道了利用金催化与铜催化相结合合成5-氨基-2H-吡咯的方法. 首先通过均相金催化异恶唑与炔酰胺反应生成α-亚胺金卡宾中间体, 再经[3+2]环加成反应合成并分离出5-氨基-3H-吡咯, 然后通过铜催化的去酰基化和基团迁移反应来实现3H-吡咯向2H-吡咯的转化. 该方法不但操作简单、反应条件温和、官能团兼容性良好, 而且还能进行克量级放大. 这项研究为合成具有重要生物活性的5-氨基-2H-吡咯化合物提供了广谱实用的合成方法.     

普莱克尼啶及其类似生物碱的研究进展

普莱克尼啶(Plakinidines)及其类似生物碱是从海洋软体动物中提取的、含有吡咯并吖啶和吡啶并吖啶稠环结构的生物碱。其中普莱克尼啶是人类从海洋生物提取物中发现的第一类含有吡咯并吖啶稠环结构的生物碱,并表现出很好的抗寄生虫和抗癌等生物活性。本文综述了普莱克尼啶及其类似生物碱的提取、分离、结构确定、生物活性以及化学合成研究进展。     

Plakinidines生物碱的研究进展

Plakinidines是从海洋生物中分离得到的一种活性物质,也是人们首次发现具有吡咯[2,3,4-kl]吖啶骨架结构的天然产物,相应的生物活性探讨与合成工作也相继地展开.在本文中,结合本课题组的合成工作报道plakinidines的发现、生物活性以及相关的合成进展.     

吡咯并[1,2-a]喹喔啉类化合物合成研究进展

吡咯并[1,2-a]喹喔啉类化合物是广泛存在于天然产物和生物活性分子中一类重要的含氮杂环化合物.因而,吡咯并[1,2-a]喹喔啉骨架,特别是取代的吡咯并[1,2-a]喹喔啉的合成具有重要理论和实际意义.较全面总结近几十年里吡咯并[1,2-a]喹喔啉和4,5-二氢吡咯并[1,2-a]喹喔啉类化合物的合成研究进展,对该领域所存在的问题和局限性进行了总结并对今后的发展作出展望.     

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.     

5-(1-芳基-1-吡咯-2-基)-1氢-四唑类化合物的合成与表征

利用阳极氧化反应, 将一系列N-芳基吡咯电氰化, 区域专一地得到吡咯氰化物2, 分离收率为76%~85%. 将其与叠氮化钠反应, 合成了一系列具有潜在血管紧张素Ⅱ受体(AT)拮抗活性的新型四唑化合物. 该合成路线的原料易得, 并以阳极氰化芳香氮杂环引入氰基为关键步骤, 可作为在芳香氮杂环上引入四唑基团的通用合成路线.     

Spectroscopic and theoretical study on peramine and some pyrrolopyrazinone compounds

The comparative analysis of IR and Raman spectra of peramine and its four derivatives in solid state was carried out. The harmonic vibrational frequencies, infrared intensities, and Raman scattering activities were calculated at density functional B3LYP methods with 6-311++G(d,p) basis set. For the predicted spectra, a potential energy distribution of normal modes was also calculated. For peramine derivatives the conjugation effect of pyrrole with pyrazinone ring was observed as a result of introduction of double bond. Moreover, ¹H NMR analysis indicated that pyrrole protons are deshielded in comparison with the pyrrolopyrazinone model ring system.     

Metal-carbenoid mediated CH-functionalization of pyrroles with methyl 2-diazo-3,3,3-trifluoropropionate

Metal-catalyzed CH-functionalization of pyrrole and its derivatives via insertion of CF3-carbene generated from methyl 2-diazo-3,3,3-trifluoropropionate was studied. The reactions are completed within few minutes upon heating in toluene in the presence of 1 mol.% of commercially available copper trifluoroacetylacetonate. These reaction conditions allow simultaneous introduction of trifluoromethyl and methyl carboxylate groups into the aromatic pyrrole ring. Conditions for C(2)-selective monofunctionalization of NH-pyrroles were developed.     

Selective Double Functionalization of meso‐Tetraphenylporphyrin Complexes on the Same Pyrrole Unit by Tandem Electrophilic/Nucleophilic Aromatic Substitution

The mono‐nitrated meso‐tetraphenylporphyrin (TPP) complex 2 could be readily functionalized on the substituted pyrrole ring with yields of up to 83%. These transformations were achieved via aromatic substitution with carbanions generated from diverse functionalized compounds containing different leaving groups ( 3a – g , Scheme 1). The resulting TPP compounds 4a – g , bearing two different β‐substituents on the same pyrrole ring, may be further manipulated. This, in turn, should allow one to tune the solubility of TPP derivatives used in photodynamic cancer therapy.     

Synthesis and biological evaluation of 3-substituted-indolin-2-one derivatives containing chloropyrrole moieties

Eighteen novel 3-substituted-indolin-2-ones containing chloropyrroles were synthesized and their biological activities were evaluated. The presence of a chlorine atom on the pyrrole ring was crucial to reduce cardiotoxicity. The presence of a 2-(ethyl-amino)ethylcarbamoyl group as a substituent at the C-4' position of the pyrrole enhanced the antitumor activities notably. IC50 values as low as 0.32, 0.67, 1.19 and 1.22 μM were achieved against non-small cell lung cancer (A549), oral epithelial (KB), melanoma (K111) and large cell lung cancer cell lines (NCI-H460), respectively.     

Preparation of pyrrole and pyrrolidine derivatives of pyrimidine. 1‐(2‐pyrimidinyl)pyrrole ‐ an inhibitor of X. phaseoli and X. malvacearum

Pyrrole and pyrrolidine derivatives of pyrimidine were prepared in which the nitrogen atom of the pyrrole or pyrrolidine ring is bonded directly to the 2‐ or 4‐carbon atom of the pyrimidine ring. Pyrrole derivatives were prepared by the dry distillation of an intimate mixture of an aminopyrimidine with mucic acid and by the reaction of a chloropyrimidine with potassium pyrrole. Pyrrolidine derivatives were prepared by the reaction of a chloropyrimidine with pyrrolidine and, in a single instance, by the catalytic hydrogenation of a pyrimidinylpyrrole. At a concentration of 200 mcg/mL, 1‐(2‐pyrimidinyl)pyrrole inhibited two plant pathogenic bacteria — Xanthomanus phaseoli (pathogenic on the bean plant) and Xanthomanus malvacearum (pathogenic on the cotton plant).     

Thermolysis of 1-dialkylaminoanthraquinones — New method for the synthesis of anthra[1, 9-bc]pyrrole derivatives

1-Dialkylaminoanthraquinones undergo cyclization to give anthra[1,9-bc]pyrrole derivatives on thermolysis in pyridine and other polar solvents. The cyclization proceeds through intramolecular rearrangement of 1-dialkylaminoanthraquinones to anthra[1,9-de]-1,3-oxazine derivatives and through subsequent contraction of the 1,3-oxazine ring to a pyrrole ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1360–1363, October, 1975.     

Synthesis and Diels-Alder reactions of the benzo[4,5]thieno [2,3-c]pyrrole ring system

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system and its derivatives, as well as their Diels-Alder reactions with DMAD and N-phenylmaleimide are reported. A new synthesis of the benzo[4,5]thieno[2,3-d]pyridazine ring system is also described.     

Synthesis of pyrrole and indole quinoxalinone and oxazinone derivatives by intramolecular copper-catalyzed reactions

Intramolecular N-arylation of pyrrole and indole carboxamides and carboxylates linked with a pendant haloarene by Cu-catalyzed reactions to synthesize pyrrole and indole quinoxalinone and oxazinone derivatives is reported. The ring closure reactions were carried out by conventional heating and MW irradiation. The use of conventional heating affords moderate to good yields of the quinoxalinone and oxazinone derivatives (34-72%), while by using MW heating the best results are obtained (41-99%).     

Synthesis of N-benzyl-des-D-ring lamellarin K via an acyl-Claisen/Paal-Knorr approach

Lamellarin K is a complex pyrrole natural product and member of the lamellarin family – a group of natural products known for their potent biological activities, such as, antiproliferative activity and inhibition of P-gp mediated drug efflux pumps. We herein describe the synthesis of the N-benzyl-des-D ring analogue of lamellarin K using a route that centres on an acyl-Claisen reaction to eventually prepare a highly-functionalised 1-aryl-4-methyl-1,4-diketone. Paal-Knorr pyrrole formation using this diketone undergoes auto-oxidation to give a fully-substituted 5-formyl pyrrole which was converted into the natural lactone B ring. Antiproliferative testing of the N-benzyl-des-D ring analogue gave an IC₅₀ of 2.63 μM against the MDA-MB-231 breast cancer cell line.