稳定烯醇结构3-氯-2-羟基-4-羰基-4-对甲苯基-2-丁烯酸乙酯的合成

以甲苯为起始原料,通过傅克-酰基化、Aldol反应合成了具有稳定烯醇结构的3-氯-2-羟基-4-羰基-4-对甲苯基-2-丁烯酸乙酯,反应过程生成了中间体3,3-二氯-2-羟基-4-羰基-4-对甲苯基丁酸乙酯,采用红外、核磁共振谱、HRMS产品进行了测定和结构表征。对反应机理进行了初步探讨。     

微波作用下1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑的合成及生物活性

采用微波和相转移催化法通过1-苯基-5-(4-苯基-1,2,4-三唑-5-巯基-3-甲硫基)四唑(2)与2-氯乙酰芳胺(3)反应高效、快速地合成了10种尚未见文献报道的1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑. 其结构经 IR, ¹H NMR, ¹³C NMR 和元素分析表征. 生物活性实验结果表明, 该类化合物在较低浓度下部分化合物对小麦芽有很好的促进作用.     

(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分

(S)-2-氨基-1,1-二苯基-1-丙醇是一种合成多种手性助剂的重要中间体,也用于外消旋屈昔多巴前体化合物的拆分。从价廉易得的L-丙氨酸出发,通过四步反应制得,总收率55.6%L-丙氨酸经甲酯化,苄氧羰基保护制得的L-2-苄羰基氨基丙酸甲酯与苯基溴化镁反应制得(S)-2-苄氧羰基氨基-1,1-二苯基-1-丙醇。是在5%Pd/C催化加氢下脱除苄氧羰基得到标题化合物。该制备方法涉及的中间体及目标化合物易于纯化,总收率高且重现性好。我们用制得的氨基醇能成功地拆分外消旋苏式屈昔多巴前体化合物3-3,4-二苄氧苯基)-N-苄氧羰基丙氨酸。     

气相色谱法测定不对称合成手性4-苯基-2-丁醇反应液中的3种组分

正手性4-苯基-2-丁醇为(R)-(-)-4-苯基-2-丁醇和(S)-(+)-4-苯基-2-丁醇的总称,是用途较广的手性药物中间体,通过它可以合成多种具有良好治疗效果的药物。如用于免疫调节的光学活性(R)-3-烷基羧酸[1]、抑制胃酸的分泌及抗胃溃疡活性的苯并噻唑类化合物[2]、合成镇静剂止痛药[3],治疗高血压     

微生物酶催化的不对称还原反应合成(S)-(+)-4-苯基-2-丁醇

以LB培养基培养Pseudomonas monteilii TA-5,将其整细胞作为生物催化剂（Cat）,催化4-苯基-2-丁酮(1)的不对称还原反应,对映选择性地合成了(S)-(+)-4-苯基-2-丁醇。在最佳反应条件［1 10 mmol·L^-1, c（Cat） 30 g cdw·L^-1, 10%丙三醇,pH 8.0, 300 r·min^-1,于30 ℃反应24 h］下,转化率82%, ee值91%。     

新型2，6-双（3，5-二取代吡唑基-1-羰基）吡啶的合成

报道了四种吡唑衍生物和它们四种新型的杂环酰胺衍生物的合成，它们是3，5-二甲基吡唑(1)，5-甲基-3-苯基吡唑(2)，3，5-二苯基吡唑(3)，5-甲基-3-二茂铁基吡唑(4)，2，6-双(3，5-二甲基吡唑基-1-羰基)吡啶(5)，2，6-双(5-甲基-3-苯基吡唑基-1-羰基)吡啶(6)，2，6-双(3，5-二苯基吡唑基-1-羰基)吡啶(7)和2，6-双(5-甲基-3-二茂铁基吡唑基-1-羰基)吡啶(8)．并对它们进行了元素分析，FT-IR，^1H NMR和^13C NMR等波谱分析．     

2-哌嗪基-4-苯基嘧啶衍生物的合成研究

以苯乙酮和苯胺衍生物为起始原料,通过缩合、环合、氯代反应,得到3种4-苯基-2-氯嘧啶衍生物,进而与苯基哌嗪盐酸盐反应,合成了12种带有不同取代基的2-哌嗪基-4-苯基嘧啶衍生物。该合成方法具有反应时间短、操作简便、副产物少的优点。各步产物均用MS,1H NMR,13C NMR表征。     

Lewis碱协助的 Lewis酸催化醇脱水合成烯烃及二氢吡喃开环合成2-肉桂基取代1,3-二羰基化合物

醇脱水是合成烯烃的重要方法之一。全球每年约有15%的苯乙烯是通过1-苯乙醇在酸性条件下脱水反应生产。虽然人们对该反应进行了较为深入的研究,但是当使用活性较高的1-苯乙醇衍生物为底物时,由于得到的取代苯乙烯产物具有较高的反应性,在脱水过程中会发生聚合而导致反应选择性降低,因此有必要探索适宜在高活性1-苯基乙醇脱水反应中应用的催化剂体系。
　　本文借助酸碱协同催化方法考察了1-(4-甲氧基苯基)乙醇制备4-甲氧基苯乙烯的反应。发现三苯基磷与 AlCl3构建的 Lewis碱/Lewis酸协同催化体系在硝基甲烷中可以接近定量的收率得到4-甲氧基苯乙烯。 Lewis碱/Lewis酸协同催化体系有效避免了4-甲氧基苯乙烯的二聚现象。底物拓展研究显示该方法具有很好的底物普适性,对多种取代苯乙烯的收率均超过80%。机理研究表明,1-(4-甲氧基苯基)乙醇在酸作用下先生成碳正离子,三苯基磷作为偶极性的电子给体不但能在一定程度上稳定该苄基碳正离子,而且抑制了其与4-甲氧基苯乙烯之间的亲电反应,进而最大化了脱质子生成4-甲氧基苯乙烯的选择性。
　　将Lewis碱协助的 Lewis酸催化提高反应选择性策略用于2-苯基-3,4-二氢吡喃衍生物合成2-肉桂基-1,3-二羰基化合物的开环反应。该类取代二氢吡喃在酸催化剂作用下也可生成苄基碳正离子,但是该中间体易受分子间和分子内亲电反应影响,反应选择性不高。而当使用单质碘/三苯基磷协同催化体系时,2-苯基-3,4-二氢吡喃衍生物能高选择性地实现开环反应,得到反式2-肉桂基-1,3-二羰基化合物。该类1,3-二羰基化合物具有丰富的反应性,是一类重要的合成子。     

5,10,15,20-四(4-羧基苯基)卟啉的微波合成

利用微波加热法,由5,10,15,20-四(4-甲氧羰基苯基)卟啉水解合成了四(4-羧基苯基)卟啉,并对反应条件进行了探讨。结果表明：以吡啶为溶剂,氢氧化钾为催化剂,以65W的微波功率辐射30rnin,可使5,10,15,20-四(4．甲氧羰基苯基)卟啉完全水解。反应时间是传统加热法用时的1/48。     

反式-3-苯基-12-取代环十二酮的合成及晶体结构

以环十二酮为原料,经2-碘酰基苯甲酸(IBX)氧化制备2-环十二烯酮,在醋酸钯和三苯基磷催化下,2-环十二烯酮与苯硼酸反应制得3-苯基环十二酮.经3-苯基环十二酮与不同试剂发生区域选择性反应制备了一系列新的3-苯基-12-取代环十二酮衍生物,采用核磁共振波谱(NMR)和液相色谱-高分辨质谱(HRMS)表征了其结构.在溶液中结晶,获得了4个代表性化合物的单晶并进行X射线衍射分析,结果表明,3-苯基-12-取代环十二酮晶体中的十二元环仍采取[3333]-2-酮构象,2个取代基为反式构型,取代基存在2种情形:2个取代基在同一条边上,苯基位于与羰基间隔1个亚甲基的β-角碳反向位,而另1个取代基位于与羰基另一侧相邻的α-角碳顺向位;或2个取代基在2条边上,苯基位于与羰基间隔1个亚甲基另一条边的β-边碳外向位,而另1个取代基位于与羰基另一侧相邻并在同一条边的α-边碳外向位,量子力学计算结果与晶体衍射分析结果一致.     

CoPc在八面沸石笼中的原位合成及性能研究

采用苯酐－尿素路线，对CoPc金属配合物在八面沸石超笼中原位合成进行了考察，并采用多种物化手段和催化反应对所制备的CoPcY进行了详细的表征。结果表明，该制备路线是一简便有效的合成路线，采用该路线可在八面沸石超笼中原位合成CoPc金属配合物并将之固定于八面沸石中。在该制备方法中合成温度、离子交换所采用的盐类型及催化剂对CoPc金属配合物在八面沸石超笼中的合成及所制备的CoPcY在环己烷氧化反应中的催化性能有很大的影响，其中180 ℃为最佳合成温度，氯化钴较适合作为交换的盐类。在八面沸石超笼中原位合成的CoPc金属配合物在温和的反应条件下对环己烷氧化具有良好催化活性，转化数TON最高可达5 000以上。     

Synthesis of a 3,4,5-trimethoxybenzoyl ester analogue of epigallocatechin-3-gallate (EGCG): a potential route to the natural product green tea catechin, EGCG

The synthesis of a trimethoxybenzoyl ester (D-ring) analogue of epigallocatechin-3-gallate (EGCG) is described. The versatile synthesis route can be used to synthesize A, B, and D ring analogues of EGCG and involves a key cyclization of the chalcone to the 3-flavene. This synthesis provides a possible route to the polyphenolic green tea natural product EGCG.     

Novel synthesis method of ester free trimethylene carbonate derivatives

Ester free poly(trimethylene carbonate) (PTMC) derivatives show biocompatibility and biodegradability and do not generate any acidic compounds after decomposition. Their syntheses methods are limited however, hampering their material application. Herein, we established a novel synthesis route of ester free trimethylene carbonate (TMC) derivatives. The novel synthesis route was described using six aldehydes and one ketone as starting compounds. The key reaction is the selective deprotection from two protected hydroxyl groups in the cyclic acetal structure by diisobutylaluminium hydride. This novel synthesis route means that it is possible to convert aldehyde group to ether groups in the side chain of TMC. Conventionally, only a substituent derived from a primary alcohol was introduced into the side chain. We therefore succeeded in decreasing the number of reaction steps from five to three, compared with the conventional route. Furthermore, the development of a novel synthesis route enabled the introduction of substituents derived from secondary alcohols, anticipating the creation of further types of ester free TMC derivatives.     

Utility of the ammonia-free Birch reduction of electron-deficient pyrroles: total synthesis of the 20s proteasome inhibitor, clasto-lactacystin beta-lactone

A new synthesis of the 20S proteasome inhibitor clasto-lactacystin beta-lactone is described. Our route to this important natural product involves the partial reduction of an electron deficient pyrrole as a key step. By judicious choice of enolate counterion, we were able to exert complete control over the stereoselectivity of the reduction/aldol reaction. Early attempts to complete the synthesis by using a C-4 methyl substituted pyrrole are described in full, together with our attempts to promote regioselective elimination of a tertiary alcohol. The lessons learnt from this first approach led us to develop another, and ultimately successful, route that introduced the C-4 methyl group at a late stage in the synthesis. Our successful route is then described and this contains several highly stereoselective steps including a cis-dihydroxylation and an enolate methylation. The final synthesis proceeds in just 13 steps and in 15 % overall yield making it an extremely efficient route to this valuable compound.     

奥斯米韦合成进展

在综述神经氨酸酶抑制剂发展现状的基础上, 重点介绍了奥斯米韦的合成研究进展: 以(−)-奎尼酸、(−)-莽草酸、D-甘露糖和由苯及其衍生物为原料合成奥斯米韦的方法; 烯类化合物经Diels-Alder 反应合成奥斯米韦的方法.     

An alternative synthesis of the non-small cell lung carcinoma drug afatinib

Afatinib (BIBW2992) is the anticancer drug developed by Boehringer Ingelheim. This work is reporting the synthesis of the afatinib using a new route by Ullmann-Goldberg reaction from corresponding 4-anilinoquinazoline iodide as the last step in the synthesis. This route was not described previously and it could be used for synthesis of afatinib analogues.     

Function-Oriented and Modular (+/−)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors

Described herein is a function-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-κB inhibitors and dependent on the local environment of the Michael acceptor moieties.     

Single-step thermal carburization synthesis of Supported molybdenum carbides from molybdenum-containing methyl-silica

A novel synthesis route to obtain highly dispersed molybdenum carbides in porous silica is described. The synthesis was carried out by a single-step heat treatment of molybdenum-containing and methyl-modified silica (Mo-M-SiO2) in argon atmosphere at 973 K. Mo-M-SiO2 precursor was facilely obtained via a one-pot synthesis route, using (NH4)6Mo7O24 4H2O (AHM) as molybdenum sources and polymethylhydrosiloxane (PMHS) as silica sources at the initial synthetic step. The optimal C/Mo molar ratio in reaction system for complete carburization of molybdenum species was 7. The carburization process of molybdenum species followed a nontopotactic route involving a MoO2 intermediate phase, which was evidenced by XRD, N2 adsorption-desorption and in situ XPS. Formation mechanism of Mo-M-SiO2 precursor was also proposed by observation of the reaction between AHM and PMHS with TEM. Furthermore, by adding TEOS into silica sources and adjusting TEOS/PMHS mass ratio, crystal phase of molybdenum carbides transferred from β-Mo2C to α-MoC1-x, and SiO2 structure changed from microporous to micro/mesoporous. Catalytic performances of samples were tested using CO hydrogenation as a probe reaction. The supported molybdenum carbides exhibited high selectivity for higher alcohol synthesis compared with bulk β-Mo2C and α-MoC1-x.     

De novo asymmetric synthesis of (−)-nanaomycin A

The de novo asymmetric total synthesis of (?)-nanaomycin A is described. The entirely linear route required only 13 steps from commercially available starting materials (3% overall yield). Key transformations include a Claisen rearrangement, an asymmetric dihydroxylation, a regioselective tosylation, a diastereoselective intramolecular Friedel-Crafts alkylation and a nitrile hydrolysis. As the route relies on a Sharpless asymmetric dihydroxylation it is equally amenable for the synthesis of (+)-nanaomycin A.     

Total synthesis of mevashuntin

The total synthesis of (±)-mevashuntin, a structurally unique naturally occurring pyrano-naphthoquinone-thiazolone, is described. The route is centered upon a late stage regioselective Diels-Alder reaction between two highly functionalized components, as well as an improved protocol for the one pot synthesis of benzothiazolones from ortho-bromoaryl isothiocyanates. The strategy results in a highly convergent route, providing access to the natural product in 11 steps from 3-(4-methoxyphenoxy)propanol and confirming its relative stereochemistry.