1α-羟基去氢表雄酮的合成与应用研究进展

1α-羟基去氢表雄酮是合成马沙骨化醇的起始原料,也是合成维生素D类衍生物关键中间体和原料,具有良好的市场前景。标题化合物的合成研究已有半个多世纪的历史,但适于工业化的合成工艺尚待于开发。按起始原料不同对标题化合物合成方法和应用进行综述。合成标题化合物起始原料主要有1,4-雄烯二酮和去氢表雄酮。以去氢表雄酮为原料的合成方法又分为化学法和微生物法。     

黄体酮合成新工艺研究

以4-雄烯-二酮为原料,经过氰化、脱水、缩酮、氢化、格式和水解反应得到甾体孕激素类药物黄体酮,重量总收率高于65%。     

去氢表雄酮合成研究进展

去氢表雄酮对生命代谢活动起着重要的调节作用,具有抗衰老、抗肿瘤、抗抑郁等作用。综述了去氢表雄酮的几种合成方法,并对合成方法进行了分析总结。     

表雄酮的合成工艺改进

表雄酮是一种甾体激素类药物的中间体。以雄烯二酮(雄甾-4-烯-3,17-二酮)为原料,经3-羰基烯酯化反应、17-羰基缩酮保护反应,再经碱性水解,不经后处理而直接用钯碳还原,集水解还原于一锅,最后在醇的酸溶液中进行水解,得到目标化合物表雄酮。通过熔点、~1HNMR、~(13)CNMR、IR对中间体和目标化合物的结构进行了表征。优化了烯酯化反应中除水剂乙酰氯加入量、雄烯二酮与醋酸酐物质的量比、温度以及缩酮保护反应中除水剂原甲酸三甲酯的加入次数。通过改进,目标化合物表雄酮总产率为51.0%(以雄烯二酮计)。此路线各步反应产率较高、后处理简单、原料价格便宜、所用试剂毒性小,符合绿色化学的要求。     

甲睾酮的合成

4-雄烯二酮经过3位醚化反应、17位β环氧反应,17位开环反应,3位水解反应得到甲睾酮,总收率高达86%,适合工业化生产。     

薯蓣皂素下游产品7-酮基去氢表雄酮醋酸酯合成进展

薯蓣皂素下游产品种繁类多,生理活性显著,7-酮基去氢表雄酮醋酸酯是人工合成的一种活性物质,文章综述了近年来以去氢表雄酮为原料的通过烯丙位氧化合成7-酮基去氢表雄酮的研究进展,其趋势是朝着方便、绿色环保方向发展。     

DHEA母液物合成雄烯二酮工艺研究

以DHEA的母液物为原料,一步沃氏氧化合成雄烯二酮(4-AD),研究了环己酮的体积、异丙醇铝的质量与DHEA母液物的质量比例为:1∶0.01∶1(V/M/M),精制溶剂为乙酸乙酯、甲醇/二氯甲烷时,雄烯二酮产品总收率达65.6%;其结构经~1H NMR和ESI-MS确证。     

去氢表雄酮吡唑衍生物的合成及抗肿瘤活性研究

以去氢表雄酮为起始原料,经Claisen-Schmidt反应,再与芳基肼类化合物反应,获得具有吡唑结构的去氢表雄酮衍生物,产率80%～90%,其结构经~1H NMR,~(13)C NMR和ESI-MS表征,并用MTT法考察了其对人前列腺癌细胞DU-145的体外抑制活性。结果表明化合物B和C对DU-145均有一定抑制活性,其中化合物B对DU-145具有较好的抑制活性。     

一类甾体22-羧酸乙酯的简易合成方法

改进了一类甾体22-羧酸乙酯化合物的合成,以去氢表雄酮为原料,经过3步反应得到产物,优化条件下总收率69%。该工艺避免了复杂的柱层析纯化过程,具有工业化生产前景。     

醋酸阿比特龙的合成

以去氢表雄酮为原料,经与水合肼缩合、碘代、再与3-吡啶溴化镁发生偶联反应、乙酰化等4步反应合成了目标产物醋酸阿比特龙,总收率为51.4%。产物结构经1 HNMR、元素分析表征。     

氟氯氰菊酯的合成

本文通过比较两种不同的合成路线介绍了氟氯氰菊酯的合成方法。以对氟苯甲醛为起始原料,经过溴化、缩醛化、醚化、水解、酯化合成氟氯氰菊酯,总收率45%。该工艺具有原料易得、反应步骤少等特点。     

Effects of Dehydroepiandrosterone (DHEA) on Hepatic Lipid Metabolism Parameters and Lipogenic Gene mRNA Expression in Broiler Chickens

The aim of the present study was to identify the effects of dehydroepiandrosterone (DHEA) on hepatic lipid metabolism parameters and lipogenic gene mRNA expression in broiler chickens. A total of 72 1-day-old broiler chicks received a common basal diet with DHEA added at either 0 (control), 5 or 20 mg/kg feed. In the present study, the hepatic triglyceride (TG) concentration was significantly lower in male and female broilers that had bed administered DHEA than in control birds. In contrast, DHEA administration caused a marked rise in the hepatic non-esterified fatty acid (NEFA) concentration in both male and female broilers and also increased lipase (HL) activity in male broilers, while in female birds, no significant differences were observed in HL activity. The expression of peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase I (CPTI) mRNA was decidedly enhanced following treatment with DHEA, and a similar tendency was also observed in the expression of acyl-Coenzyme A oxidase 1 (ACOX1). However, no significant differences were observed in the expression of either sterol regulatory element binding protein-1c (SREBP-1c) or acetyl CoA carboxylase (ACC) mRNA, except for a decline in the expression of ACC in females treated with 5 mg DHEA/kg. Numerous peroxisomes without a core and an increased number of peroxisomes were evident during morphological observations of broiler livers, in animals that had been treated with DHEA. Overall, the results of the present study indicated that DHEA accelerated lipid catabolism by direct regulation of hepatic lipid metabolism and by induction of relevant gene expression.     

对氯苯甲酰氯的合成

对氯苯甲酰氯是合成杀菌剂烯酰吗啉和药物吲哚美辛的一个重要中间体。以对氯甲苯为原料,经氯化、水解反应合成对氯苯甲酰氯,总收率为94.6%,产品含量为99.3%。     

顺式那格列奈的合成

首次报道了抗糖尿病新药那格列奈异构体-顺式那格列奈的合成方法。实验中将4-异丙基苯甲酸溶于醋酸中,在催化剂作用下氢化得4-异丙基环己甲酸的顺反异构体混合物,经过硫脲及N-羟基琥珀酰亚胺处理而得顺式4-异丙基环己甲酸琥珀酯,再与D-苯丙氨酸甲酯盐酸盐反应,然后于碱性条件下水解得到顺式那格列奈.以起始原料4-异丙基苯甲酸计,顺式顺式那格列奈纯度为98.8%,总收率为7.63%。     

4''''-羟基-4-联苯甲酸的合成

以4-羟基联苯为原料,经酯化、傅-克酰基化、相转移催化下的苄基化、氯仿反应、催化氢解等反应,合成了标题化合物,总收率57.8%.化合物4'-苄氧基-4-乙酰基联苯、4'-苄氧基-4-联苯甲酸的结构经 1HNMR、IR、MS及元素分析确证.与文献比较,该路线选择性好、产率较高.     

托拉塞米合成研究

以4-羟基吡啶为起始原料。依次经磺化、氯化、酰胺化、取代、缩合反应得到成品。总收率为37．9％,并对合成工艺进行了优化,工艺适合于工业化生产。     

4-溴甲基二苯甲酮的合成研究

以 4 甲基二苯甲酮和溴素为原料 ,四氯化碳为反应和重结晶溶剂 ,经溴化反应合成了 4 溴甲基二苯甲酮。优惠工艺条件 :反应温度 80℃ ,反应时间 4h ,原料配比为 1∶1(mol) ,产品收率≥ 5 8% ,含量≥ 99%。     

Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.