手性金属络合物催化剂在不对称合成中的应用

不对称合成是当前有机合成中热门研究领域，利用手性金属络合物催化剂催化不对称硅氢化、烷基化，以烯烃、酮、亚胺、醛等合成手性醇、手性胺、手性酮等具有很好的工业应用前景。本文论述了手性金属络合物催化剂在不对称硅氢化反应及其在二烷基锌对醛的不对称烷基化反应中的应用。     

不对称催化及药物合成——2001年诺贝尔化学奖的青睐

介绍了 2 0 0 1年度诺贝尔化学奖得主在催化不对称合成领域的研究成果     

D-脯氨酰胺的不对称合成研究

以L-脯氨酸为起始原料,运用不对称转换的方法,以S-酒石酸为拆分剂,合成D-脯氨酸。然后进一步以手性源技术通过上保护基、酯化、氨化和脱保护基等步骤,不对称合成D-脯氨酰胺。选择苄氧羰基氟为保护基,研究酰胺化的最佳实验条件是：氟甲酸乙酯与N-苄氧羰基-D-脯氨酸的物质的量此为1．1。温度-5℃,通氨1h（300mL／min）后,静置36h,用Pd／C催化剂通氢气脱保护基。D-脯氨酰胺的收率达到78．7％,比原不上保护基的路线收率提高1倍以上,光学纯度为99．3％,不易发生消旋等副反应。同时研究了pH值、温度及消旋时间对D-脯氨酰胺消旋的影响。     

有机钛化合物在不对称合成中的应用

综述了近年来有机钛化合物在不对称合成中的一些应用,阐述了有机钛化合物在不对称加成反应、不对称氧化反应、不对称硅氰化反应等方面的应用.     

去甲去氢斑蝥素新衍生物的合成

以顺丁烯二酸酐和呋喃为起始原料,经Diels-Alder[4+2]缩合反应,制备去甲去氢斑蝥素,同时在去甲去氢斑蝥素分子中引入电负性较大的氧原子、氮原子。去甲去氢斑蝥素经SN2取代、缩合和过氧酸氧化三步反应,合成了5,6-环氧去甲去氢斑蝥素衍生物,去甲去氢斑蝥素经S_N2取代、缩合、过氧酸氧化和取代四步反应,得到5,6-二羟基去甲去氢斑蝥素衍生物。所得化合物均经~1HNMR和ESI-MS确证。     

双功能有机硫脲催化剂在不对称合成中的应用

综述了双功能有机硫脲催化剂的发现,及其在Michael加成反应、Mannich反应及其它不对称合成反应中的应用,并展望了其应用前景。     

有机金属试剂与不对称合成

本文综述了有机金属试剂在不对称有纲合成中的应用,介绍了应用手性试剂进行不对称有机合成,以及应用手性催化剂进行不对称合成的方法。     

手性催化在不对称合成中的发展

介绍了手性化合物的重要性及其发展情况,从手性分子的制备、手性有机小分子催化的应用等方面总结了手性分子的研究进展,指出了手性分子的发展方向。     

Saquinavir mesylate的不对称合成研究进展

综述了治疗艾滋病药物Saquinavir mesylate的研究概况,对Saquinavir mesylate的不对称合成方法进行了归纳和总结,重点介绍了不对称还原、不对称醇醛缩合和Sharpless环氧化等反应在Saquinavir mesylate不对称合成中的应用。对今后Saquinavir mesylate不对称合成的研究动向进行了展望。     

Practical Consequences of Non‐Linear Effects in Asymmetric Synthesis

The fundamental principles of non‐linear effects (NLE) are reviewed. Particular emphasis is placed on the case of asymmetric amplification, since it allows one to perform useful chemistry with a non‐enantiopure chiral auxiliary. A strong asymmetric depletion in a catalytic reaction may lead to an underestimation of the actual enantioselectivity of the fully resolved ligand. The study of NLE's is also proving useful as a mechanistic tool in asymmetric catalysis. Similar concepts may be extended to chiral reagents or to kinetic resolution. 1. What is a Non‐Linear Effect in Asymmetric Synthesis? 2. The Conditions for Observing a Non‐Linear Effect in Enantioselective Catalysis 3. Some Simple Models of NLE in Enantioselective Catalysis 4. Comparison of the Sizes of Asymmetric Amplifications 5. Rates and Non‐Linear Effects in Asymmetric Catalysis 6. Non‐Linear Effects Involving Chiral Reagents 7. Mechanistic Applications of Non‐Linear Effects 8. Synthetic Applications 9. Concluding Remarks     

Synthesis and Biological Evaluation of Ferrocenylquinoline as a Potential Antileishmanial Agent

The emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. Herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against Leishmania donovani. 7‐Chloro‐N‐[2‐(1H‐5‐ferrocenyl‐1,2,3‐triazol‐1‐yl)ethyl]quinolin‐4‐amine ( 1 ) was generated by coupling an iron(II) ethynylferrocene species with 4‐(2‐ethylazido)amino‐7‐chloroquinoline using click chemistry. The synthesized compound 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Compound 1 showed promising anti‐promastigote activity, with an IC₅₀ value of 15.26 μM and no cytotoxicity toward host splenocytes. From the battery of tests conducted in this study, it appears that this compound induces parasite death by promoting oxidative stress and depolarizing the mitochondrial membrane potential, thereby triggering apoptosis. These results suggest that ferrocenylquinoline 1 is a suitable lead for the development of new antileishmanial drugs.     

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2–4%, a DEX content of 50–85 μg/mg, and a degree of succinylation of 64–68%. The size of the obtained particles was 400–1100 nm, and the ζ-potential was −30 to −33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8–10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.     

Synthesis and Biological Evaluation of Imidazopyridine–Oxindole Conjugates as Microtubule‐Targeting Agents

A library of imidazopyridine–oxindole conjugates was synthesised and investigated for anticancer activity against various human cancer cell lines. Some of the tested compounds, such as 10 a , 10 e , 10 f , and 10 k , exhibited promising antiproliferative activity with GI₅₀ values ranging from 0.17 to 9.31 μM . Flow cytometric analysis showed that MCF‐7 cells treated by these compounds arrested in the G₂/M phase of the cell cycle in a concentration‐dependent manner. More particularly, compound 10 f displayed a remarkable inhibitory effect on tubulin polymerisation. All the compounds depolarised mitochondrial membrane potential and caused apoptosis. These results are further supported by the decreased phosphorylation of Akt at Ser473. Studies on embryonic development revealed that the lead compounds 10 f and 10 k caused delay in the development of zebra fish embryos. Docking of compound 10 f with tubulin protein suggested that the imidazo[1,2‐a]pyridine moiety occupies the colchicine binding site of tubulin.     

一种非对称双尾阳离子表面活性剂的合成及表面活性研究

以N,N-二甲基丙二胺、1-溴-十四烷、辛酸等为原料,通过酰化和季铵化反应合成了3个非对称双尾阳离子表面活性剂,用IR和1HNMR表征了中间体和目标产物。酰胺化反应的最佳条件为:投料比n(正辛酸)∶n(N,N-二甲基丙二胺)=1∶1.1,反应温度为120℃,反应时间为10 h。目标产物的最低表面张力(γCMC)均在20～30mN/m,临界胶束浓度(CMC)均在10-5～10-6 mol/L,γCMC和CMC均远低于结构类似单尾表面活性剂的γCMC和CMC。双尾阳离子表面活性剂的泡沫半衰期(T1/2)为22～31 min,泡沫稳定性强于单尾表面活性剂。     

新型甲硝唑-苯腙类化合物的设计、合成及抗菌活性研究

以甲硝唑、对羟基苯甲醛及取代肼为原料,经过3步反应,以较高产率合成得到一类新型的甲硝唑-苯腙类化合物,其结构经~1HNMR、~(13)CNMR和元素分析确证,所得化合物经抗菌活性筛选研究。结果表明,大部分化合物都具有较强的抗菌活性。其中以(E)-4-(2-(4-(2-(2-甲基-5-硝基-1H-咪唑-1-基)乙氧基)苯亚甲基)肼基)苯磺酰胺活性最好,对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和枯草芽孢杆菌的最低抑制浓度分别为1.56、0.78、0.39和0.39μg/m L。     

Asymmetric Synthesis of 2,3,4‐Trisubstituted Functionalised Tetrahydrofurans via an Organocatalytic Michael Addition as Key Step

The organocatalytic Michael addition of various aldehydes to (2E,4E)‐ethyl 5‐nitropenta‐2,4‐dienoate has been achieved under the catalysis of diphenylprolinol trimethylsilyl ether furnishing the products in good to excellent yields (61–94%) and high stereoselectivities (dr up to >98:2, ee=97 to >99%). Starting from these Michael adducts, 2,3,4‐trisubstituted functionalized tetrahydrofurans are available in two steps by reduction of the aldehyde followed by an intramolecular oxa‐Michael addition in good yields (54–76%) and stereoselectivities (dr up to >95:5, ee=97 to >99%).     

新型白藜芦醇吡唑衍生物的合成工艺研究

在氢氧化钠存在下,白藜芦醇衍生物(E)-2,4-二甲氧基-6-(4-甲氧基苯乙烯基)苯甲醛与丙酮经Claisen-Schmidt缩合反应合成化合物B,收率为77.68%。化合物B和对甲苯磺酰肼在氢氧化钠为缚酸剂,(n-Bu)4NBr为相转移催化剂且用量为化合物B的2 equiv的条件下,于80℃反应12 h,得到产物(E)-3-(2-(4-甲氧基苯乙烯基)-4,6-二甲氧基苯基)-5-甲基-1H-吡唑,收率为59.13%。该方法具有合成成本低、工艺操作简便和经济性好等优点。     

α-芳基丙酸不对称合成研究进展

对近年来α—芳基丙酸类非甾体抗炎药光学纯品不对称合成方法从傅氏烷基化、重排反应、α—位的甲基化反应、Sharpless反应、格氏交叉偶联反应、氢化反应、羰化反应、酶催化反应这八个方面进行了总结和概述(特别是(S)—萘普生的合成),从中反映近年来不对称合成的新趋势。     

不对称合成中催化剂的回收利用研究进展

由于不对称合成中所用催化剂多数为金属配体,合成困难且价格昂贵,因此对不对称合成中催化剂的回收与再利用的研究有重大意义,本文对这一研究领域的现状作一概述。     

一种应用催化不对称硼氢化反应合成S-布洛芬的新方法

以4-异丁基苯乙酮为原料,发展了一条简洁的S-布洛芬不对称合成方法。经4步反应得到具有光学活性的S-布洛芬,光学纯度e.e.达到66%,总收率为61%,其关键步骤为一步催化不对称硼氢化1,1-二取代末端烯烃。