海洋生物中的体化合物的研究进展

甾体化合物是一类具有显著生理活性且广泛存在于自然界中的天然化合物。本文对近年来从海洋生物中分离得到的甾体化合物,根据其结构特征对它们进行了分类总结,并对其生物活性进行了阐述,以期对甾体药物的研究开发提供有用的参考。     

海洋生物中甾体化合物的研究进展

甾体化合物是一类具有显著生理活性且广泛存在于自然界中的天然化合物。本文对近年来从海洋生物中分离得到的甾体化合物,根据其结构特征对它们进行了分类总结,并对其生物活性进行了阐述,以期对甾体药物的研究开发提供有用的参考。     

海星动物化学成份的研究-罗氏海盘车中的皂苷元

报导了从罗氏海盘车中分离得到二个甾体皂苷元;20(R)-5α-孕甾-9(11)-烯-3β,6α,20-三醇和5α-孕甾-9(11)-烯-3β,6α-二醇-20-酮,并测定了它们的结构.     

天然产物的生物合成

<正> 天然产物的化学成份中有一些基本物质是各种生物体内部普遍存在的,象碳水化合物、蛋白质、核酸等,这些类型不是很多。第二级次生的构成物质类型则比较多,在这类天然产物的化学里研究最多的是脂肪酸及其衍生物以及含氮有机化合物,即生物碱,还有甾体、萜类、天然色素等。这些物质从表面上看起来好象互相没有关联,化学结构差别也很大,很难想象它们在生物体内的来源是相互有关的。     

海洋生物中具有生理活性的多羟基甾醇

多羟基甾醇是一类具有显著生理活性的天然化合物,广泛地存在于海洋生物当中.根据甾体中所含羟基的数目进行分类,综述了近几年来从海洋生物中分离得到的具有生理活性的多羟基甾醇的研究进展.     

海绵 Rhaphisia pallida Ridley 中甾类成分的质谱分析

介绍从南沙海域采集的ＲｈａｐｈｉｓｉａｐａｌｌｉｄａＲｉｄｌｅｙ海绵样品中分离得到的混合甾类样品，采用气相色谱质谱法鉴定其组分。应用质谱裂解规律结合计算机检索确定了十一种甾体化合物的结构，其中两个是首次在海绵生物中发现的甾体激素化合物。     

剑麻皂素中惕告吉宁和核柯配质的高速液相色谱分析

剑麻皂素中的惕告吉宁(Tigogenin)和核柯配质(Hecogenin)是合成甾体激素药物的重要天然原料之一,随着甾体激素合成制药工业的迅速发展,其需要量正日益增长。剑麻皂素中除主要成分惕告吉宁和核柯配质外,尚有少量的其他皂甙元。由于甾体皂甙元的结构非常相似,用一般化学方法较难分离和测定,近年来多采用     

6β-卤代-19-羟基-4-雄甾烯-3,17-双酮的分子内亲核取代反应

具有4-烯-3-酮结构的6β-卤代甾体化合物经强酸处理可以转变为大约1∶1的6β与6α卤代甾体化合物的混合物,混合物经分步结晶、柱层或薄层分离可以得到一定量的6α-卤代化合物。例如,6β-溴-4-雄甾烯-3,17-双酮在含有盐酸的甲醇中,45℃反应1小时,约50%的化合物转化为6α-溴代化合物。在寻     

胆固醇氢亚磷酸酯缀合物的简便合成

许多甾体磷酸酯具有重要的生物活性,例如脂质膜和甾体激素中的甾体磷酸酯缀合物.利用一些甾体类物质的体内转运机制,可以增加药物的靶向性,同时将糖和甾体相连可以增加甾体类药物水溶性.胆固醇是许多生物膜的关键结构单元,同时又是甾体激素和胆酸的生物合成前体.本文报道一种简便的合成胆固醇氢亚磷酸酯缀合物的合成方法,从这些氢亚磷酸酯出发可以进一步得到许多具有生物学意义的磷酸酯缀合物.     

甾体类天然产物^13C—核磁共振数据的计算机检索

本文报道了一种小型甾体类天然产物~(13)C-NMR数据库及检索系统。系统具有名称、结构、化学位移和分子式等多种检索功能。能有效地辅助人们对甾体类天然产物~(13)C-NMR图谱的解析。系统采用BASIC语言编写,编译后运行。经在IBM PC/XT机上运行得到了比较满意的结果。     

Isolation, biological significance, synthesis, and cytotoxic evaluation of new natural parathiosteroids A-C and analogues from the soft coral Paragorgia sp

Three unusual new steroid thioesters, parathiosteroids A-C (1a-3a), were isolated from the 2-propanol extract of the soft coral Paragorgia sp. collected in Madagascar. Their structures, determined by detailed spectroscopic analysis, were confirmed by synthesis and represent the first isolation of natural steroids bearing a C22 thioester in their side chain. These compounds displayed cytotoxicity against a panel of three human tumor cell lines at the micromolar level. The preparation of several analogues revealed structure/activity relationships in this type of steroids, for example, that the XCH2CH2NHCOCH3 moiety (X = S, O, NH) in the side chain is essential for the antiproliferative activity, and a low degree of oxidation in the A-ring results in higher bioactivity. These natural products could be biosynthetic intermediates in the steroid side chain degradation pathway involving activation with CoA and beta-oxidations.     

Antiferromagnetic interaction achieved by a 3-D supramolecular CuII complex with pyrazino-fused TTF as the ligand, [CuCl2(BP-TTF)

The diffusion reaction of TBA2Cu(II)Cl4 (TBA = tetrabutylammonium) and a N-containing organic donor, BP-TTF [=bis(pyrazino)tetrathiafulvalene], yielded a 3-D supramolecular Cu complex, [CuCl2(BP-TTF)] (1). The magnetic measurement of 1 exhibits an antiferromagnetic interaction by fitting a Bonner-Fisher model from 2 to 300 K with S = 1/2 and J = -3.5 K between Cu(IotaIota) mediated by self-assembling donor columns.     

Optical properties of bis(pyrazino)tetrathiafulvalene salts

The optical reflectance and absorption spectra of (BPTTF)₂BF₄[where BPTTF is bis(pyrazino) tetrathiafulvalene] and similar salts are reported for a wide spectral region.     

An efficient one-pot three-step domino synthesis of substituted bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones)

A convenient and efficient one-pot three-step domino approach to bis(pyrazinothienopyrimidinones) from ethyl 3-(triphenylphosphoranylideneamino)-thieno[2,3-b]pyrazine-6-carboxylate 1 has been developed. In this method, treatment of phosphazene 1 with a mixture of isocyanates, nitrogen, sulfur, and oxygen bis(nucleophiles) and K₂CO₃ in refluxing THF regioselectively furnishes the corresponding bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones) in satisfactory to good yields. This methodology is highly versatile and efficient for the generation of these functionalized bis(triheterocyclic) compounds that are not readily available by other synthetic methods.     

Molecular recognition thermodynamics and structural elucidation of interactions between steroids and bridged bis(beta-cyclodextrin)s

A series of bridged bis(beta-cyclodextrin(CD))s (2-7) were synthesized, i.e., bridged bis(beta-CD)s 2 and 3 bearing binaphthyl or biquinoline tethers and bridged bis(beta-CD)s 4-7 possessing dithiobis(benzoyl) tether, and their complex stability constants (KS), enthalpy (DeltaH degrees), and entropy changes (DeltaS degrees) for the 1:2 inclusion complexation with representative steroids, deoxycholate, cholate, glycocholate, and taurocholate, have been determined in an aqueous phosphate buffer solution of pH 7.20 at 298.15 K by means of titration microcalorimetry. The original conformations of bridged bis(beta-cyclodextrin)s were investigated by circular dichroism and 1H ROESY spectroscopy. Structures of the inclusion complexes between steroids and bridged bis(beta-CD)s in solution were elucidated by 2D NMR experiments, indicating that anionic groups of two steroid molecules penetrate, respectively, into the two hydrophobic CD cavities in one 6,6'-bridged bis(beta-CD) molecule from the secondary rim to give a 1:2 binding mode upon inclusion complexation. The results obtained from titration microcalorimetry and 2D NMR experiments jointly demonstrate that bridged bis(beta-CD)s 2, 3 and 5-7 tethered by protonated amino group possessing different substituted groups can enhance not only the molecular binding ability toward steroids by electrostatic interaction but also molecular selectivity. Thermodynamically, the resulting 1:2 bis(beta-CD)-steroid complexes are formed by an enthalpy-driven process, accompanied by smaller entropy loss. The increased complex stability mainly results from enthalpy gain, accompanied by large conformational change and extensive desolvation effects for the 1:2 inclusion complexation between bis(beta-CD)s and steroids.     

An expedient synthesis of the proposed biosynthetic precursor of the oxepine natural product,janoxepin

An efficient synthetic route to the putative biosynthetic intermediate of the anti-plasmodial natural product janoxepin is described. This novel enamine-containing pyrazino[2,1-b]quinazoline-3,6-dione, and its synthetic precursors, should be of value in studies to elucidate the biosynthetic pathway leading to the oxepine family of natural products. The cornerstones of the synthesis are amide coupling, pyrazino[2,1-b]quinazoline-3,6-dione construction and aldol introduction of the enamine.     

Synthesis of a peralkynylated pyrazino[2,3-g]quinoxaline

[structure: see text] The synthesis of a hexaethynyl[2,3-g]pyrazinoquinoxaline and its crystal structure are reported. Starting from tetraaminobenzoquinone, condensation to bis(triisopropylsilyl)hexadiyne-2,3-dione affords 2,3,7,8-tetrakis(triisopropylsilylethynyl)pyrazino[2,3-g]quinoxaline-5,10-dione. Reaction with TIPS-CC-Li followed by reduction with hypophosphite in the presence of KI furnished the title molecule in a yield of 62%. Pd catalysis is not involved in any of these steps.     

Synthesis of (+)-cortistatin A

Cortistatin A is a marine steroid with highly selective and perhaps mechanistically unique antiangiogenic activity. Herein we report a synthesis of this natural product by way of "cortistatinone", an intermediate ideally suited for investigating the key pharmacophore of the cortistatin family. The synthesis begins with a terrestrial steroid and traverses a route to cortistatin A through the discovery of unique chemical reactivity. Specifically, we demonstrate the first example of a directed, geminal C-H bisoxidation, a new fragmentation cascade to access expanded B-ring steroid systems, a chemoselective cyclization to install the hallmark oxabicycle of the cortistatin family, and a remarkably selective hydrogenation reaction, which should find extensive use in future syntheses of the cortistatins and designed analogues. The synthesis displays a level of brevity, efficiency, and practicality that will be crucial in evaluating the medicinal potential of this fascinating class of marine steroids.     

Recent advances (1995-2005) in fluorinated pharmaceuticals based on natural products

This present report is devoted to the recent advances, in these last 10 years, in fluorinated analogues of natural products developed as pharmaceuticals, marketed, registered or in clinical development. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids and prostaglandins.     

Antimycobacterial natural products

This review covers the literature published between January 1990 and December 2002 (inclusive) for natural products with reported antimycobacterial activity, with 248 citations to 352 compounds isolated from both terrestrial and marine sources The compounds are presented in order of chemical type, namely lipids/fatty acids and simple aromatics phenolics and acetogenic quinones, peptides, alkaloids, terpenes (monoterpenoids, diterpenes, sesquiterpenes, sesterterpenes and triterpenes) and steroids.