New biologically active rubiginones from Streptomyces sp

Four new polyketides, named rubiginone D2 (2), 4-O-acetyl-rubiginone D2 (3), rubiginone H (6) and rubiginone I (7) were isolated from the cultures of Streptomyces sp. (strain G? N1/5). Their structures were established by a detailed spectroscopic analysis. The absolute configuration of 3 was determined by derivatization with chiral acids (Helmchen's method). The rubiginones inhibit the growth of some Gram-positive bacteria and are cytostatically active against different tumor cell lines.     

Genoketides A1 and A2, new octaketides and biosynthetic intermediates of chrysophanol produced by Streptomyces sp. AK 671

The new aromatic polyketides genoketide A1, genoketide A2 and prechrysophanol glucuronide are biosynthetic intermediates of the octaketide chrysophanol. They were isolated from the alkaliphilic strain Streptomyces sp. AK 671 together with the new metabolite chrysophanol glucuronide. The structures of the compounds were elucidated by mass spectrometry and NMR methods. Genoketide A2 exhibited a slight and prechrysophanol glucuronide a more pronounced inhibition of the proliferation of L5178y lymphoma cells.     

17 -Propadienyl, 17 -propynyl, and 17 -trifluoropropynyl analogs of 6,6-difluoronorethindrone

The synthesis of analogs of 6,6-difluoronorethindrone (la) is reported. The new compounds, each of which are potent oral progestational agents, are ( )-6,6-difluoronorgestrel (lb), 17 beta-hydroxy-6,6-difluoro-17alpha-propadienyl-4-estren-3-one (lc), 17beta-hydroxy-6,6-difluoro-17alpha-(1-propynyl)-4-estren-3-one (ld), and 17 beta-hydroxy-6,6-difluoro-17alpha-(3,3,3-trifluoropropynyl)-4-estren-3-o ne (le). The 6,6-gem-difluoro group is an important means for enhancing the progestational activity of parent compounds. Compounds lc,ld, and le were prepared from a common precursor, 6,6-difluoro-4-estrene-3,17-dione 3-ethylene ketal. The findings indicate that 6,6-difluoro steroids are stable towards a variety of reagents. The experimental procedures are summarized.     

组合生物合成研究进展

组合生物合成是通过对微生物代谢途径中一些酶的编码基因进行操作,从而获得许多新的“非天然”天然产物。本文重点介绍聚酮合酶（PKSs）和非核糖体多肽合酶（NRPSs）的分类、作用机制及其杂合系统在组合生物合成应用研究中相关报道。另外,对于PKSs和NRPSs在大肠埃希荫中的异源表达也作了简单介绍。     

Aurafuron A and B, new bioactive polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria). Fermentation, isolation, physico-chemical properties, structure and biological activity

New antibiotic polyketides, named aurafuron A (1) and B (2) were isolated from culture extracts of myxobacteria of the species Stigmatella aurantiaca and Archangium gephyra, strain Ar 10844. By multi-step chromatography 1 and 2 were separated from a variety of other non-related co-metabolites, and their structures elucidated by spectroscopic methods as new 5-alkenyl-3 3(2H)-furanones. Aurafurons inhibited the growth of some filamentous fungi and additionally, aurafuron B was weakly active against few Gram-positive bacteria. Both compounds also showed cytotoxic activity against the mouse fibroblast cell line L929.     

Two glucosylated angucyclines from deep-sea-derived Streptomyces sp. PKU-MA01297

Angucyclines are aromatic polyketides produced by type II polyketide synthase (PKS) exclusively from actinomycetes. These natural products contain hydrolyzable sugar moieties that attach to various positions of the polyketide skeleton and expand the structural diversity. We here report the isolation of two new angucyclines (1 and 2) from the deep-sea-derived Streptomycessp. PKU-MA01297, which was isolated from a sediment sample collected at a depth of 3202 meters from the Indian Ocean. The structures of the two new compounds were elucidated based on comprehensive methods, including NMR, MS and CD analysis. Compounds 1 and 2 featured a 1-O-β-d-glucopyranosyl moiety that has not been reported for angucyclines. Several biological activity assays, including antibacterial, cytotoxicity and anti-inflammatory assays, were carried out, and compounds 1 and 2 showed no activities. These results set the stage for biosynthetic research and more biological activity assays in the future.     

Neuraminidase inhibitory polyketides from the marine-derived fungus Phoma herbarum

Two new polyketides, arthropsadiol C (1) and massarilactone H (2), together with six known derivatives (3-8) were isolated from the culture broth of the marine-derived fungus Phoma herbarum. Their structures were elucidated on the basis of spectroscopic methods, including 2D?NMR techniques. Compounds 2, 4, 5, and 8 showed moderate neuraminidase inhibitory activity with IC(50) values ranging from 4.15 to 9.16?μM.     

雷斯青霉菌中的一个新萘醌类化合物

目的 基于OSMAC策略指导下研究雷斯青霉菌Penicillium raistrickii次级代谢产物的多样性及抗肿瘤活性研究。方法 采用大米作为培养基,静置发酵获得粗提物。对粗提物采用硅胶柱层析、LH20凝胶色谱、半制备高效液相色谱(PHPLC)和半制备薄层色谱法(PTLC)等方法,对总浸膏进行分离纯化;利用波谱技术包括核磁共振(NMR)和质谱(MS)等技术结合文献报道数据,确定所得化合物结构;利用CCK8法评价所得化合物对HepG2肿瘤细胞增殖抑制活性。结果 从雷斯青霉菌中共分离鉴定了10个化合物,包括2个萘醌类化合物(1~2),4个色原酮类化合物(3~6)和4个??酮类化合物(7~10),其结构分别鉴定为7-carbomethoxy-2,8-dimethoxy-5-hydroxy-l,4-naphthoquinone (1),2,7-dimethoxy-5-hydroxy-1,4-naphthoquinone (2),5-甲基-2-乙基-7-羟基色原酮 (3)、2,5-二甲基-7-羟基色原酮(4),2-甲基-5-羧甲基-7-羟基色原酮(5),lamellicolic anhydride (6),1,3,6-trihydroxy-8-methyl xanthone (7),1,6-dihydroxy-3-methoxy-8-methyl xanthone (8),1,5,6-trihydroxy-3-methoxy-8-methyl xanthone (9)和1,3,5,6-tetrhydroxy-8-methyl xanthone (10)。结论 从雷斯青霉菌大米静置发酵物中分离得到了10个聚酮类化合物化合物,其中化合物1为新萘醌衍生物,化合物3为新色原酮类天然产物。所得化合物对HepG2细胞无增殖抑制活性。     

Cladosins F and G,two new hybrid polyketides from the deep-sea-derived Cladosporium sphaerospermum 2005-01-E3

Two new fungal hybrid polyketides, cladosins F (1) and G (2), with rare 6(3)-enamino-8,10-dihydroxy-tetraketide system were discovered from the deep-sea-derived fungus Cladosporium sphaerospermum 2005-01-E3 guided by OSMAC approach. Their structures were elucidated on the basis of comprehensive spectroscopic analyses, and cytotoxicity, antitubercular, anti-influenza A H1N1 virus, and NF-κB inhibitory activities were evaluated.     

Identification of impurities in the production of terbinafine hydrochloride

The purity of the parent substance of (E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine (terbinafine) is evaluated via TLC identification of the main impurities appearing during its synthesis via alkylation of N-methylnaphth-1-ylmethylamine with 1-chloro-6,6-dimethyl-2-hept-2-en-4-yne The possible formation of impurities including N-methyl-N,N-di(methylnaphth-1-yl)amine, N-methylnaphth-1-ylmethylamine, N-methylnaphth-2-ylmethylamine, (E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine, (Z)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine, (E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-2-ylmethylamine, and (Z)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-2-ylmethylamine was confirmed by means of countersynthesis. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 8, pp. 45–47, August, 2006.     

Acetophenone derivatives and sesquiterpene from Euphorbia ebracteolata

Two new acetophenone derivatives and a new sesquiterpene, along with four known acetophenone compounds, were isolated from the roots of Euphorbia ebracteolata. The structures of the new compounds were identified as 2,2',4,4'-tetrahydroxy-6,6'-dimethoxy-3,3'-dimethyl-7,5'-bisacetophenone, 2,4-dihydroxy-6-methoxy-3-methylacetophenone 4-O-alpha-L-arabinofuranosyl-(1-->6)-beta- D-glucopyranoside and decahydro-1a,4a,7,7-tetramethyl-1H-cycloprop[e]azulene-2,5-diol (1a R,2 R,4a S,5 S,7a R,7b R) using 1D and 2D NMR spectroscopy and X-ray crystallography.     

Two new compounds from Cynanchum amplexicaule

A new phenolic glycoside, sinapic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and a new sucrose ester, 6,6'-di-O-sinapoylsurcose (3), were isolated from the roots of Cynanchum amplexicaule (Sieb. et Zucc.), along with two known compounds, 6-O-[E]-sinapoyl-d-glucopyranoside (2) and sibricose A1 (4). Their structures were elucidated on the basis of both chemical and spectroscopic methods.     

Steroids and polyketides from Uvaria hamiltonii stem bark

Two known steroids, stigmasterol and 6b-hydroxystigmasta-4,22-dien-3-one (1) and two unusual polyketides, cis-4-hydroxymellein (2) and trans-4-hydroxymellein (3) were isolated from the stem bark of Uvaria hamiltonii. The structures of the compounds were elucidated independently by high-resolution 2D-NMR techniques and confirmed by comparison with previously reported values.     

Two new ɑ-pyrone derivatives from the endophytic Diaporthe sp. ECN371

Journal of Natural Medicines - Diaportholides A (1) and B (2), two polyketides with ɑ-pyrone moieties, were isolated from the cultures of an endophytic Diaporthe sp. ECN371 isolated from Orixa...     

TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282

Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.     

组合生物合成聚酮类药物研究进展

在筛选和发展新型微生物药物方面组合生物合成日益成为生物、化学和医药界关注的重点。基于聚酮类（PK）天然产物的独特化学结构和良好生物活性，研究它们的生物合成机制，将为合理化遗传修饰生物合成途径获得结构类似物提供遗传和生物化学的基础，实现利用现代生物学和化学的技术手段在微生物体内进行药物开发的目的。现综述近年来组合生物合成技术的基本原理、聚酮合酶的基本作用机制以及合成途径的改造情况等。     

Polyketides from the fungus Penicillium decumbens

Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and trichopyrone B (2), together with two known polyketides, sorbicillin (3) and penicillone A (4), have been isolated from the cultures broth of the fungus Penicillium decumbens. Their structures were elucidated by extensive spectroscopic analysis. All isolated compounds were evaluated for their antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal activity toward Candida albicans Y0109 with a MIC value of 50 μM. Moreover, compounds 3 and 4 exhibited selective cytotoxicity against the human hepatocellular carcinoma (QGY-7703) cell line with the IC₅₀ values of 32.5 and 22.8 μM, respectively.     

Total syntheses of surinone B,alatanones A–B,and trineurone A

The total syntheses of four polyketides, surinone B (1), alatanones A–B (2–3), and trineurone A (4) were accomplished through an efficient and unified strategy via one-pot C-acylation reaction coupling 1,3-cyclohexadiones with EDC-activated acids under mild conditions. Alatanone A (2) was found to be a potent anti-microbial agent against Gram-positive and Gram-negative bacteria with MIC 31.25 μg/ml while alatanone B (3) was found to be a potent anti-fungal agent against Cladosporium cladosporioides with MIC 62.5 μg/ml compared to cycloheximide MIC 125 μg/ml. Our methodology allows performing kilogram scale of these scarce polyketides for the development of new antimicrobials.     

Tripodalsporormielones A–C,unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems

A chemical investigation on Sporormiella sp. led to the isolation and structural elucidation of tripodalsporormielones A–C (1–3), a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bridged and fused ring systems. These polyketides with cage-like skeletons were characterized as a high non-protonated carbon-containing system, which resulted in few HMBC correlations observed and made the accurate structures hard to be obtained by NMR. Especially, some signals of non-protonated sp² carbons are weak and even unobservable in compound 1. In order to establish the structure of 1, the calculated NMR with DP4 evaluation was applied to determine the structure from the plausible structure candidates obtained from the detailed NMR analysis. Based on NMR experiments and calculated NMR, the structures of isolated compounds were established and confirmed by X-ray technology. Through chiral isolation, the optically pure enantiomers of 1 and 3 were obtained, and their absolute configurations were determined based on ECD quantum chemical calculation. Based on the isolated compounds and our previous work, 1–3 would be derived from 3-methylorcinaldehyde, and their plausible biosynthetic mechanism was proposed. Furthermore, 1 exhibited obvious short-term memory improvement activity on an Alzheimer''s disease fly model.KEY WORDS: Tripodalsporormielones, Cage-like polyketides, 3-Methylorcinaldehyde, Alzheimer''s disease     

当归中新的二聚苯酞衍生物

目的深入研究中药当归Angelica sinensis的化学成分。方法用硅胶柱色谱法和光谱分析法分离和鉴定化学成分。结果除3个已知的苯酞类结构外，从当归中又分离到1个新的二聚苯酞衍生物和一对几何异构体，经光谱分析鉴定其结构分别为Z-3′,8′,3′a,7′a-四氢-6,3′,7,7′a–二聚藁本内酯-8′-酮(1)、Z,Z′-6,6′,7,3′a-二聚藁本内酯(2)和2的8位几何异构体(3)。结论化合物1为新的二聚苯酞类衍生物，3为首次从当归中鉴定的二聚苯酞类衍生物。