3-脱克拉定糖-3-酮基-6-O-甲基-10,11-脱氢-12-O-咪唑酰基-2''''-苯甲酰基红霉素A的合成

目的 合成制备泰利霉素的关键中间体。方法 以3-脱克拉定糖-3-酮基-6-O-甲基-2’-苯甲酰基红霉素A为起始原料，经过甲磺酯化、碱消除、咪唑酰基化三步成功地合成关键中间体3-脱克拉定糖-3-酮基-6—O-甲基-10，11-脱氢-12-O-咪酰基-2’-苯甲酰基红霉素A，并进行了工艺改进。结果与结论 新的合成工艺与未改进时相比，总收率提高10％，为科研和工业化生产奠定基础。     

3-脱克拉定糖-3-酮基-6-O-甲基-10,11-脱氢-12-O-咪唑酰基-2′-苯甲酰基红霉素A的合成

目的合成制备泰利霉素的关键中间体。方法以3-脱克拉定糖-3-酮基-6-O-甲基-2′-苯甲酰基红霉素A为起始原料,经过甲磺酯化、碱消除、咪唑酰基化三步成功地合成关键中间体3-脱克拉定糖-3-酮基-6-O-甲基-10,11-脱氢-12-O-咪酰基-2′-苯甲酰基红霉素A,并进行了工艺改进。结果与结论新的合成工艺与未改进时相比,总收率提高10%,为科研和工业化生产奠定基础。     

几种药物合成新工艺及制备新方法

酮内酯红霉素是第三代红霉素的杰出代表，该类化合物对耐药性病原体具有良好活性。其代表药物泰利霉素在临床上的成功使用，将大环内酯类药物的研究推向了新的高度。制备酮内酯化合物的必要步骤是将克拉霉素的3-克拉定糖水解脱除，     

2''''-乙酰基-3-酮基-10,11-脱水-6-O-甲氧基红霉素的合成

目的:合成泰利霉素中间体2'-乙酰基-3-酮基-10,11-脱水-6-O-甲氧基红霉素.方法:以6-O-甲氧基红霉素为起始原料,经脱水、酸水解、乙酰化和氧化得到目标产物.结果:以6-O-甲氧基红霉素计,总收率79.9%.目标产物的光谱数据与文献报道一致.结论:该方法合成操作简单,反应条件温和.     

第三代大环内酯类抗生素的结构改造及合成方法

酮内酯类抗生素是具有大环内酯结构的红霉素衍生物。大量耐药病原菌的迅速出现使红霉素类半合成抗生素临床应用出现了挑战,也促使了针对耐药菌的第三代酮内酯类药物的研发并取得了丰硕的研究成果,其代表药物为泰利霉素和喹红霉素。本文综述了近年来对酮内酯类抗生素C-6位、C-5位糖环、三环类、C-11,12位及C-12位等处结构修饰方面的新进展,重点介绍了第三代酮内酯半合成抗生素合成的方法研究。     

2’，4＂-二乙酰基红霉素-9-O-杂环烷基肟衍生物的合成及体内抗菌活性

目的设计合成2’，4＂-二乙酰基红霉素-9-O-杂环烷基肟衍生物，并对其体内抗菌活性进行评价。方法以红霉素为原料，经9位羰基肟化、肟羟基烷基化、2’，4＂-二羟基乙酰化3步反应制得目标化合物；选取有代表性的8个化合物评价其对小鼠感染所致败血症的治疗作用。结果与结论共制得18个未见文献报道的目标化合物，经MS,^1H—NMR确证结构；该类化合物具有较好的抗菌活性，其中化合物9n的活性优于对照药罗红霉素和克拉霉素。     

制备3-O-去红霉糖红霉素衍生物的新途径

目的 开发一种合成酮基内酯和酰基内酯常用中间体3-O-去红霉糖衍生物的新方法。方法 红霉素9(E)-（O-烷基)-肟衍生物与对甲基苯磺酸一水合物在DMF中于室温下反应选择性水解红霉素得到相应的3-O-去红霉糖衍生物。结果 高收率得到3-O-去红霉糖衍生物并利用MS、^13C-NMR、^1H—NMB和IR确定了其结构。结论 该方法是制备3-O-去红霉糖红霉素衍生物的简捷、有效的新途径。     

3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的 3位羟基红霉素衍生物。方法　以红霉素A为原料 ,经 9位酮基肟化 ,9位肟羟基 ,2′位羟基和 3′位二甲胺基同时苄基化 ,6位羟基甲基化 ,水解去 3位克拉定糖 ,氢化还原脱苄基 ,对甲基苄基或邻氯苄基取代 9位肟羟基等 6步反应 ,制得 3 羟基 6 O 甲基红霉素 9 肟基衍生物 ,其结构经1 3 CNMR ,FAB MS确证。结果　共制得 7个化合物 ,对其中 4个 (5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　 5 ,7,8对部分红霉素诱导耐药菌有一定的活性     

C克拉霉素的合成

首先用邻氯氯苄保护红霉素A9-肟衍生物,其次用三甲基硅胺保护2＇,4"-羟基,最后选择性甲基化6-羟基制得克拉霉素.     

C克拉霉素的合成

首先用邻氯氯苄保护红霉素A9—肟衍生物,其次用三甲基硅胺保护2′,4″-羟基,最后选择性甲基化6—羟基制得克拉霉素。     

Three new lignans from the seeds of Saussurea involucrata

Three new lignans, arctigenin-4-O-(6'-O-acetyl-β-d-glucoside) (1), arctigenin-4-O-(2'-O-acetyl-β-d-glucoside) (2), and arctigenin-4-O-(3'-O-acetyl-β-d-glucoside) (3), together with two known lignans, were isolated from the seeds of Saussurea involucrata. Their structures were established by spectroscopic methods, mainly 1D and 2D NMR, and mass spectral analysis.     

MGCD0103的合成工艺改进

目的改进MGCD0103的合成工艺。方法以3-乙酰吡啶为原料,与N,N-二甲基甲酰胺二甲缩醛缩合后,与4-胍基甲基-苯甲酸环合,再与邻苯二胺缩合得到MGCD0103。结果与结论目标化合物经1H-NMR和MS鉴定,改进后的工艺合成路线缩短、反应条件温和,总收率为42%(以3-乙酰吡啶计,提高了16%),生产成本显著降低,更适合工业化生产。     

2-Acetylpyridine thiosemicarbazones. 10. 2-Propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine thiosemicarbazones as potential antimalarial agents

In view of the antimalarial properties observed for many 2-acetylpyridine thiosemicarbazones, a series of N4,N4-disubstituted thiosemicarbazones derived from 2-propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine was prepared for evaluation against the malaria parasite, Plasmodium berghei, in the mouse. The thiosemicarbazones were made by the reaction of methyl hydrazinecarbodithioate with a 2-acylpyridine to give the intermediate methyl 3-[1-2-pyridinyl)alkylidene]hydrazinecarbodithioates. Reaction of the latter with 3-azabicyclo[3.2.2]nonane, 1-(2-pyridinyl)piperazine, or 1H-hexahydroazepine gave the requisite thiosemicarbazones. The three thiosemicarbazones derived from 3-azabicyclo[3.2.2]nonane were most effective, the greatest potency being exhibited by 3-azabicyclo-[3.2.2]nonane-3-thiocarboxylic acid 2-[1-(2-pyridinyl)butylidene]hydrazide (4) which cured 4/5 mice at a dose of 160 mg/kg. In contrast to the related thiosemicarbazones derived from 2-acetylpyridine, virtually no toxic effects were observed in the series described here.     

2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents

In view of the antimalarial activity in mice of 2-acetylpyridine thiosemicarbazones, a series of analogous 1-oxides was prepared for evaluation. Their synthesis was achieved by the reaction of 2-acetylpyridine 1-oxide with methyl hydrazinecarbodithioate to give methyl 3-[1-(2-pyridinyl 1-oxide)ethylidene]hydrazinecarbodithioate (II). Reaction of the latter intermediate with secondary amines afforded the desired 2-acetylpyridine 1-oxide thiosemicarbazones (III). Reduction of the azomethine linkage of II with NaBH4 gave methyl 3-[1-(2-pyridinyl 1-oxide)ethyl]-hydrazinecarbodithioate (IV) whose S-methyl group was then displaced by amines to give a 1-[1-(2-pyridinyl 1-oxide)ethyl]thiosemicarbazide, V. Antimalarial activity of III was evaluated against both Plasmodium berghei in the mouse and Plasmodium falciparum in an automated in vitro test system. In both cases, 2-acetylpyridine 1-oxide thiosemicarbazones were found to be less active than the corresponding de-1-oxide analogues. When compounds V were evaluated against Plasmodium berghei in the mouse, a diminution of activity was similarly seen in comparison to the analogues not bearing the 1-oxide moiety.     

Synthesis and biological activity of certain derivatives of oxazinomycin and related oxadiazole nucleosides

Oxazinomycin was converted into 2',3',5'-tri-O-acetyloxazinomycin (2) and 2',3'-O-isopropylideneoxazinomycin (3), respectively. Compound 3 was iodinated and reduced to provide 5'-deoxy-2',3'-O-isopropylideneoxazinomycin (5) which, after acid hydrolysis, provided 5'-deoxyoxazinomycin (6). Alternatively, the iodination of oxazinomycin followed by catalytic hydrogenation also provided 6. Oxazinomycin was treated with 2-acetoxybenzoyl chloride to provide 3'-O-acetyl-2'-chloro-2'-deoxyoxazinomycin (8) which, after reduction with tributyltin hydride, provided 3'-O-acetyl-2'-deoxyoxazinomycin (9). Oxazinomycin was also converted into oxazinomycin 5'-phosphate (10) and into O4,2'-anhydrooxazinomycin (11). 1,2,4-Oxadiazole-3,5-dione (12) was glycosylated to provide 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-oxadiazole-3,5-dione (13) which, after deacetylation, provided 2-beta-D-ribofuranosyl-1,2,4-oxadiazole-3,5-dione (14). Similarly, 12 provided 2-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3,5-dione (17); 14 was also converted into the corresponding 2',3'-O-isopropylidene derivative 15. Compound 14 showed significant antiviral activity against herpes simplex virus type 1, in vitro.     

A potent multisubstrate analogue inhibitor of human thymidylate synthetase

The synthesis of an 8-deazafolate analogue of the intermediate in the methylation of 2'-deoxyuridylate is described. Alkylation of diethyl 5,6,7,8-tetrahydro-8-deazafolate with 3'-O-acetyl-5-(bromomethyl)-2'-deoxyuridine 5'-[bis-(trichlorethyl) phosphate], followed by removal of the trichloroethyl groups with a Zn/Cu couple and mild saponification, gave the target inhibitor N-[4-[[[2-amino-3,4,5,6,7, 8-hexahydro-4-oxo-5-[(2'-deoxyuridin-5-yl)methyl]-pyrido[3,2-d] pyrimidin-6-yl]methyl]amino]benzoyl]-L-glutamic acid 5'-monophosphate. The free nucleoside and the 5'-(methyl phosphate) diester were similarly prepared. Each of these reactions yielded a pair of diastereoisomers about C-6 of the reduced deazafolate in approximately a 1:1 ratio. These diastereoisomeric mixtures were evaluated as inhibitors of thymidylate synthetase derived from human tumor (HeLa) cells. The 5'-monophosphate was a potent inhibitor, competitive with respect to both 2'-deoxyuridylate (Ki = 0.06 microM) and tetrahydrofolate (Ki = 0.25 microM). In contrast, the nucleoside and the nucleotide methyl ester were poorer inhibitors by more than 3 orders of magnitude, attesting to the importance of the anionic function at the nucleoside 5'-position in the affinity of an inhibitor for the enzyme active site.     

3-吡啶乙酸盐酸盐的合成

目的:合成3-吡啶乙酸盐酸盐.方法:以烟酸为起始原料,经酯化、缩合反应制得3-乙酰吡啶.3-乙酰吡啶经3-吡啶硫代乙酰吗啉,再水解、酸化得到3-吡啶乙酸盐酸盐.结果与结论:反应条件温和,原料价廉易得,适合工业化生产,以烟酸计,总收率达51.0%.     

替比夫定3'-O-乙酰基-5'-O-苯基-N-烷基磷酰胺类化合物的合成及体外活性的评价(英文)

本文合成了一系列替比夫定3′-O-乙酰基-5′-O-苯基-N-烷基磷酰胺类化合物,用EI-MS,~1H NMR和~(13)C NMR确证了这些化合物的结果。我们评价了这些化合物在体外的活性。在合成的化合物中,化合物6d和6f的活性比替比夫定强。     

黄花败酱中甙元与单糖链皂甙的分离鉴定

从黄花败酱根茎和根的丙酮提取物中用柱层析方法分离出3个单体化合物,经化学反应和光谱分析鉴定为:齐墩果酸、常春藤皂甙元和常春藤皂甙元-3-0(2'-0-乙酰基)-α-L-阿位伯吡喃糖甙.     

Gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones: synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase

A series of gallium(III) and iron(III) complexes with five different 4N-substituted alpha-N-heterocyclic thiosemicarbazones, viz., 2-acetylpyridine N,N-dimethylthiosemicarbazone (1), 2-acetylpyridine N-pyrrolidinylthiosemicarbazone (2), acetylpyrazine N,N-dimethylthiosemicarbazone (3), acetylpyrazine N-pyrrolidinylthiosemicarbazone (4), and acetylpyrazine N-piperidinylthiosemicarbazone (5), with the general formula [GaLCl2] (HL = 1 and 2) and [ML2][Y] (M = Ga, HL = 1-5, Y = PF6; M = Fe, HL = 1-5, Y = FeCl4 and PF6) were synthesized and characterized by elemental analysis, a number of spectroscopic methods (NMR, IR, UV-vis), mass spectrometry, and X-ray crystallography. The in vitro antitumor potency was studied in two human cancer cell lines (41M and SK-BR-3). The central metal ions exert pronounced effects in a divergent manner: gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands. The capacity of ligand 1 and its Ga(III) and Fe(III) complexes to destroy the tyrosyl radical of the presumed target ribonucleotide reductase is reported.