S38-62脂肪胺的氮杂MichaeI反应Varala R等[Synlett,2006．（10）：1549]

脂肪胺和α，β-不饱和羰基化合物的水溶液，以3mol％硝酸铈铵为催化剂，室温搅拌制得相应的B．氨基羰基化合物。环状仲胺5～30min即可完成；芳香胺不反应。20例收率55％～99％。     

(2β,3α,16β,17β)-3,17-双乙酰氧基-2,16-双哌啶基-5α-雄甾烷的合成

目的合成泮库溴铵和维库溴铵的中间体(2β,3α,16β,17β)-3,17-双乙酰氧基-2,16-双哌啶基-5α-雄甾烷。方法以表雄酮为原料,经磺酰化、消除、乙酰化、环氧化、取代、乙酰化反应合成目标化合物。结果所得产物及中间体经核磁共振谱确认。结论所设计合成路线可行,总收率30.4%,可用于工业生产。     

罗库溴铵的合成工艺研究

目的研究罗库溴铵的合成工艺。方法以2β-（4-吗啉基）-16β-（1-毗咯烷基）-3α,17β-二羟基-5α-雄甾烷为原料,经乙酰化,再选择性水解得到17p乙酰化物,然后与烯丙基溴成盐得到罗库淡铵。考察了乙酰化、选择性水解的条件,同时分离得到3a,17β-二乙酰化物。结果与结论罗库决铵及其中间体的结构经核磁共振氢谱（1H-NMR）、碳谱（^13C-NMR）,质谱（ESI-MS）确证,总收率59．6％。     

从醛合成芳香酯或酰胺

以醇或仲胺为溶剂，碱性条件下，带吸电子基的芳香醛与丙酮氰醇25℃反应3h，可分别得相应的酯或酰胺。酯24例收率58％～92％，酰胺3例收率54％～63％。α，β-不饱和醛在上述反应条件下得相应的饱和酯，9例收率57％～93％。     

萘酚用硝酸铈铵氧化生成联萘酚

2-萘酚在甲醇或乙腈中加硝酸铈铵室温反应 10～ 15 h,可高收率地氧化偶联生成相应的联萘酚。 4例收率 89%～94%。但 2 -萘酚和 3-羟基 - 2 -萘酸甲酯的反应收率仅 47%萘酚用硝酸铈铵氧化生成联萘酚@王先恒     

阿加曲班的合成方法研究

通过硝基-L-精氨酸与3-甲基喹啉-8-磺酰氯缩合,再与（2R,4R）-4-甲基-2-哌啶甲酸乙酯缩合,经过酯水解,氢化,精制共五步反应,高收率地合成了抗血栓药物阿加曲班,该合成方法操作简单,工艺稳定,产品纯度较好,适合工业化生产。     

苯乙哌啶合成的改进

目的：改进苯乙哌啶的合成方法,使之更适合工业化生产。方法,以N,N－双（β-氯乙基）对甲苯磺酰胺为原料,利用液－液相转移催化方法制得1－对甲苯磺酰基－4－氰基哌啶,再经水解,酯化,缩合,成盐等步骤,合成了苯乙哌啶。结果：总收率可达51．8％,结论：此合成方法适合工业化生产。     

(2R,4R)-4-甲基-2-哌啶甲酸乙酯的合成工艺改进

目的 优化(2R,4R)-4-甲基-2-哌啶甲酸乙酯的合成工艺.方法 以S-(-)-α-甲基苄胺为原料,与乙醛酸乙酯反应得到[(S)-1-苯乙基亚胺基]乙酸乙酯,与异戊二烯进行环合后,再经不对称氢化和脱保护反应制得(2R,4R)-4-甲基-2-哌啶甲酸乙酯.结果 总收率从17.0％提高至47.6％.结论 本工艺可有效地降低生产成本.     

口服低分子量非肽类胃素抑制剂阿利克仑的合成研究

本文通过对胃素抑制剂阿利克仑合成的三个重要中间体（2R）-3-甲基-2-（4-甲氧基-3-（3-甲氧丙氧基）苄基）-1-丁醇（中间体1）、（2S,4E）-异丙基-5-氯-4-戊烯酸甲酯（中间体2）、3-氨基-2,2-二甲基丙酰胺（中间体3）的合成路线分别从原料、反应条件、收率等方面对每条路线优劣进行了评价,以求找到最佳的工业化生产合成路线。     

爱维莫潘关键中间体的合成

目的研究爱维莫潘关键中间体2-[(S)-2-{[(3R,4R)-4-(3-羟基苯基)-3,4-二甲基哌啶基]甲基}-3-苯基丙酰氨基]乙酸乙酯的合成工艺。方法以(3R,4R)-3-(3,4-二甲基-4-哌啶基)苯酚为起始原料,经加成、缩合、水解、酰化得到目标产物。结果经4步合成了目标产物,总收率为27%,目标化合物结构经1H-NMR确证。结论本合成方法原料易得,反应条件温和,适合大规模制备。     

一种β，γ-不饱和醛的合成及其光化学反应研究

目的设计合成β,γ-不饱和醛,并研究其光化学反应机制,为天然产物及其中间体的光化学合成提供新的参考。方法以异丁醛为原料,经缩合、醛基保护、氧化、Wittig反应、脱水、脱保护基6步反应制得目标化合物。用高压汞灯照射目标化合物后所得产物与β,γ-不饱和甲基酮进行比较分析。结果目标化合物的结构经高分辨质谱、核磁共振谱确证。目标化合物经光照后发生NorrishI型裂解反应,与β,γ-不饱和甲基酮相比,没有发生ODPM重排反应。结论甲基对β,γ-不饱和酮（醛）的光化学反应行为有一定的影响。     

头霉素关键中间体7-MAC的合成方法改进

目的改进头霉素关键中间体7α-甲氧基-7β-氨基-3-[（1-甲基-1H-四氮唑-5-基）硫甲基]头孢-3-烯4-羧酸二苯甲酯（7-MAC）的合成方法。方法以7-氨基-3-乙酰氧甲基头孢烯酸（7-ACA）为原料,经亲核取代反应合成3-（1-甲基-1胁四氮唑-5-基）硫甲基-7-氨基头孢烯酸（2）,2经取代．消除反应、酯化反应制得7-甲硫亚胺-3-[（1-甲基-1H-四氮唑-5-基）硫甲基]头孢-3-烯4-羧酸二苯甲酯（5）,在中间体5的7α位引入甲氧基制得目标化合物7-MAC。结果与结论目标化合物的结构经质谱、核磁共振氢谱确证,总收率为60％以上,纯度为99．1％,透光率高于75％。该方法反应条件温和,得到的产品质量好,有利于工业化生产。     

抗2型糖尿病药西他列汀关键手性中间体的合成研究

目的合成2型糖尿病治疗药西他列汀的关键手性中间体。方法以2,4,5-三氟苯乙酸为原料,与2,2-二甲基-1,3-二烷-4,6-二酮缩合、脱羧得到3-氧代-4-(2,4,5-三氟苯基)丁酸甲酯,然后与R-α-苯乙胺缩合、不对称还原、脱除苄基保护基,再经Boc保护、水解得到西他列汀关键手性中间体(R)-3-(叔丁氧羰基氨基)-4-(2,4,5-三氟苯基)丁酸。结果与结论以总收率59.5%合成了西他列汀关键手性中间体,该合成路线具有步骤少、操作简便、收率高、立体选择性好、反应条件温和的特点。     

Novozym435催化布洛芬甲酯的不对称醇解反应

目的制备S(+)-布洛芬。方法以布洛芬甲酯为原料,利用酶催化的不对称转酯反应,将R(-)-布洛芬甲酯转化为R(-)-布洛芬丁酯,反应条件:布洛芬甲酯,10 g(100 mmol);Novozym 435,10 g;正丁醇,5.9 g(80 mmol);温度,39℃;时间,8~10h。结果不对称转酯反应的收率为83%,将得到的S(+)-布洛芬甲酯进行水解得S(+)-布洛芬,其收率为90%,光学纯为93%ee。结论该本反应体系下,酶可以被回收利用,绿色经济,该方法有工业放大的潜力。     

左旋盐酸去甲基苯环壬酯的合成新方法

目的 合成新型 M4 受体选择性拮抗剂左旋盐酸去甲基苯环壬酯。方法 以苄胺为原料制备 N,N-二乙氧基甲基苄胺,该苄胺与环己酮反应、选择性还原,再与(R)-α-苯基-α-环戊基-α-羟基乙酸甲酯反应,经氢化、成盐得到目标产物左旋盐酸去甲基苯环壬酯,总收率为 8.0%。结果与结论 目标化合物的结构经元素分析、核磁共振氢谱、质谱确证。新方法操作简便,以新旧合成路线中共有的贵重原料(R)-α-苯基-α-环戊基-α-羟基乙酸甲酯计算,产品收率较原方法提高了10.6%,降低了成本,且利于环保。     

非达司他的合成工艺改进

目的改进醛糖还原酶抑制剂非达司他的合成工艺和提高收率。方法以对氟苯甲醚和马来酸酐为起始原料,经傅-克反应、关环、酰化,得到(2S)-6-氟-3,4-二氢-4-羰基-N-[(S)-1-苯乙基]-2H-苯并吡喃-2-羧酸胺,再用浓HCl水解得羧酸,然后和乙腈及碳酸铵关环成螺环化合物,再和正丙醇成酯,然后和氨气的甲醇溶液氨解,经过8步反应得目标化合物非达司他。结果总收率从5.1%提高到26.7%(以对氟苯甲醚计),目标化合物的结构经IR、MS和1H-NMR谱确证。结论非达司他的改进工艺适合于工业化生产,提高了工业化生产的批产量。     

Thiol reactivity and its impact on the ciliate toxicity of α,β-unsaturated aldehydes, ketones, and esters

A recently introduced chemoassay has been used to determine second-order rate constants of the electrophile-nucleophile reaction of 15 α,β-unsaturated aldehydes with glutathione. The respective kGSH values vary for more than 3 orders of magnitude, and are within the range determined previously for 31 α,β-unsaturated ketones and esters. Structure-reactivity analyses yield distinct relationships between kGSH and structural features of the compounds. Moreover, increasing kGSH increases the aldehyde toxicity toward ciliates in terms of 48 h-EC50 values (effective concentration yielding 50% growth inhibition of Tetrahymena pyriformis within 48 h). A respective log-log regression equation including both kGSH and the octanol/water partition coefficient, Kow, yields a squared correlation coefficient of 0.96. Comparative analysis with corresponding data for 15 ketones and 16 esters reveals systematic differences between the three compound classes with regard to the individual contributions of hydrophobicity and electrophilic reactivity to aquatic toxicity. The former is particularly pronounced for aldehydes, while the ester toxicity is largely governed by reactivity, with ketones showing an intermediate pattern that is more similar to the one of esters than of aldehydes. It follows that within the Michael acceptor domain of α,β-unsaturated carbonyls, a distinction between aldehydes and nonaldehydic derivatives appears necessary when employing electrophilic reactivity as a component for the quantitative prediction of their reactive toxicity toward aquatic organisms.     

Natural Moroccan clays: Comparative study of their application as recyclable catalysts in Knoevenagel condensation

Natural Moroccan clay samples from different regions were purified via simple washing, activated and extensively analyzed by various characterization techniques. A comparative study of these clays as recyclable heterogeneous catalysts for the Knoevenagel condensation was undertaken in EtOH/water as solvent under mild conditions; high yield of the desired α,β-unsaturated products was obtained in a short reaction period (~ 30 min). The recyclable solid catalyst was effective for several runs indicating that these purified clays are potentially eco-friendly heterogeneous catalysts; assorted α,β-unsaturated carbonyl compounds were synthetized in high yields (~ 98%) at 40 °C.     

The mycotoxin patulin reacts with DNA bases with and without previous conjugation to GSH: implication for related α,β-unsaturated carbonyl compounds?

The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and products derived thereof, is known to induce gene, chromosome, and genome mutations in vitro, its mutagenicity correlating inversely with intracellular GSH levels. Thus, the reactivity of PAT against DNA bases and nucleosides in the absence and presence of GSH and glutathione S-transferases (GSTs) was investigated under cell-free conditions using HPLC mass spectrometry techniques for identification of reaction products. Adduct formation with all four nucleobases as well as with purine base nucleosides occurred even in the presence of GSH, revealing several adducts of PAT, mono- and disubstituted with nucleobases/nucleosides as well as novel GSH–PAT adducts. In addition, novel mixed GSH–PAT–nucleobase adducts were observed. These adducts exhibited a ketohexanoic acid-type structure of the PAT molecule, C6 substituted with GSH and linking C1 of PAT with nitrogens of nucleobases/nucleosides via an amide bond. Formation of GSH–PAT–adenine adducts was not prevented by GSTs, and excess of GSH needed to reduce their formation was higher than for PAT–adenine adducts. The formation of mixed GSH–DNA base adducts has not been described for PAT or any other α,β-unsaturated carbonyl before, although the reaction mechanism seems to be applicable to a variety of α,β-unsaturated carbonyls occurring in food and in the environment.     

蒙古黄芪化学成分研究

目的研究蒙古黄芪的化学成分。方法采用硅胶柱色谱、凝胶柱色谱方法进行分离纯化,利用波谱分析法结合理化性质确定化合物结构。结果从蒙古黄芪的乙酸乙酯和正丁醇萃取部分中共分离得到14个化合物,分别鉴定为（6aR,11R）-9,10-二甲氧基紫檀烷-3-O-β-D-葡萄糖苷（1）,（3R）-2′-羟基-3′,4′-二甲氧基异黄烷-7-O-β-D-葡萄糖苷（2）,5′-羟基-3′-甲氧基异黄酮-7-O-β-D-葡萄糖苷（3）,芒柄花苷（4）,（6aR,11R）-3-羟基-9,10-二甲氧基紫檀烷（5）,（3R）-7,2′-二羟基-3′,4′-二甲氧基异黄烷（6）,5′,7-二羟基-3′-甲氧基异黄酮（7）,芒柄花素（8）,黄芪甲苷（9）,黄芪皂苷II（10）,蔗糖（11）,腺嘌呤核苷（12）,十六烷酸单甘油酯（13）,十六烷酸（14）。结论化合物5,7,11～14为首次从黄芪属植物中分离得到,化合物6为首次从蒙古黄芪中分离得到。