分光光度法测定环氧化物浓度与环氧化物水解酶活性

研究了在弱碱性条件下 ,利用环氧化物与 4- (对硝基 )苄基吡啶之间的显色反应测定环氧化物含量 ,进而计算环氧化物水解酶活性的分光光度法。对于缩水甘油苯基醚 ,其最低检出浓度为 4.5 μmol/L,所生成染料的摩尔吸光系数 ε为 2 .2 0× 1 0 3L· mol- 1· cm- 1。在 4.5～ 30 0 μmol/L的浓度范围内 ,测量的精密度可达 0 .9%。     

二氧化碳与环氧化物共聚催化剂研究进展

二氧化碳是主要的温室气体,也是最丰富的C1资源.利用二氧化碳与环氧化物共聚生成可生物降解的聚碳酸酯是目前研究的热点之一.就目前的研究情况而言,二氧化碳与环氧化物共聚反应存在的主要问题是催化效率低、催化剂成本高、反应条件苛刻、共聚物产率较低以及催化剂分离复杂等.我们分类综述了二氧化碳与环氧化物共聚的新型催化体系,并探讨了各类催化体系的优缺点,对二氧化碳的资源化利用具有重要的应用价值.     

手性催化的环氧化物立体选择性开环反应

手性催化的环氧化物立体选择性开环反应可以用来制备多种具光学活性的化合物, 因而成为有机合成中极为重要的方法之一. 多种亲核试剂都已成功应用于此类反应. 综述了近十年来环氧化物的立体选择性开环反应方面的一些最新研究进展.     

戊二酸锌体系催化合成二氧化碳基聚碳酸酯研究进展

二氧化碳(CO2)是一种无毒无害、性质稳定、可再生的C1资源.近年来,以CO2为原料合成的CO2基聚酯受到了广泛关注.其中,戊二酸锌催化CO2和环氧化物共聚生成聚碳酸酯成为CO2高值转化的途径之一(特别是戊二酸锌催化CO2和环氧化物共聚,包括引入酸酐、环酯等三元共聚).我们综述了近年来戊二酸锌催化CO2基聚合反应的研究进展,对催化剂发展、结构、活性和产物性能等进行了系统的总结,分析了戊二酸锌催化剂在聚合反应过程中的优势和不足,最后对戊二酸锌催化剂的发展、挑战等进行了展望分析.     

苯乙烯及其衍生物的生物氨羟化反应用于β-氨基醇的高效合成（英文）

氨基醇是非常重要的手性砌块,广泛用于药物、天然产物、氨基酸及其手性助剂的合成.迄今为止,超过300000种含有此类结构单元的化合物已被报道,其中包括2000多种天然产物、80多种已获批准的药物以及超过100种候选药物.鉴于β-氨基醇的重要作用,对映选择性高效合成β-氨基醇具有非常重大的意义.过去几十年,研究人员一直致力于β-氨基醇高效合成方法的开发.其中,通过利用过量的胺作为胺供体直接与环氧化物进行氨解反应,是合成β-氨基醇最为实用和认可的方法之一.此外,科学家也开发了使用各种路易斯酸或在不同有机溶剂中反应的化学法来提高环氧化物氨解反应的效率.然而,这些方法普遍存在反应温度高、催化剂用量大、催化剂对水敏感以及有机溶剂危害大等缺陷.为了解决这些问题,研究人员进一步开发出了水溶液体系中不依赖催化剂的环氧化物氨解反应,用于氨基醇高效合成.但该方法仍然需要以高反应活性的环氧化物作为起始原料,导致其在选择性控制和后期应用方面存在一定的问题.此外,环氧化物(尤其是手性环氧化物)难以制备,通常需要金属催化剂在苛刻的反应条件下进行.相比之下,以廉价易得的烯烃作为底物,通过Sharpless不对称胺羟化...     

双波长微板法测定细胞悬浮液中的环氧化物

用双波长微板法研究了缓冲溶液与细胞悬浮液中吸光度与环氧化物浓度的关系,通过分析比较发现,在两种体系中的回归曲线相互平行。据此,可用缓冲体系中所测结果绘制标准曲线,计算细胞悬浮液中环氧化物的含量。在建立了双波长微板法测定混浊体系中环氧化物的基础上,环氧化物水解酶活力可以方便快速的检测。     

二氧化碳共聚物的合成,性质和应用

二氧化碳是开发中的重要的碳资源,它的一个有效利用方式是和环氧化物等单体共聚生成脂肪族聚碳酸酯。该反应现已能够较顺利地实现。反应中加入第三单体、扩链剂、调节剂,可以使共聚物具有不同的化学结构,以及能随意控制分子量和官能度。在了解反应系统的相平衡特性和共聚动力学以后,可以聚合过程的计算机模拟。使用交联,共混复合或网络互穿等手段,能够使产物具有各种不同的性能。二氧化碳共聚物已在许多方面获得重要的应用,是     

超临界二氧化碳中马来酸锌催化合成环状碳酸酯

在超临界二氧化碳中, 利用马来酸锌催化二氧化碳与环氧化物反应合成环状碳酸酯. 单独使用马来酸锌作为催化剂时, 对二氧化碳与环氧丙烷反应的催化活性较低, 而在DBU、DMAP、三乙胺、吡啶、咪唑或4-氨基吡啶等有机碱的存在下, 反应活性较高, 产物的收率得到明显提高. 有机碱作用的强弱顺序为DBU>Et3N>咪唑>4-氨基吡啶>DMAP>吡啶. 在压力为8 MPa, 温度110 ℃, 反应时间48 h条件下, 马来酸锌与DBU组成的二元催化系统可以催化二氧化碳与环氧丙烷反应, 得到83.4%产率的碳酸丙烯酯. 该二元系统也能催化其它环氧化物高产率地转化为相应的环状碳酸酯.     

有机溶剂/缓冲液双相体系中绿豆环氧化物水解酶催化环氧苯乙烯不对称水解反应

研究了有机溶剂/缓冲液双相体系中绿豆环氧化物水解酶高立体选择性地催化外消旋环氧苯乙烯水解生成(R)-苯基乙二醇反应.结果表明,与单水相反应体系相比,有机溶剂/缓冲液双相反应体系不仅有效地抑制环氧苯乙烯的非酶水解反应,而且明显提高底物的浓度,产物的收率和ee值更高.在所考察的不同有机溶剂中,正己烷不仅能较好地溶解底物,而...     

环氧水解酶在不对称合成中的应用

环氧水解酶是一种普遍存在于生物体内的酶,它能选择性水解环氧生成相应的手性二醇。这种酶在催化反应中通常显示出十分高的对映立体选择性,生成高光学活性的环氧和二醇。近年来国际上采用微生物来源的环氧水解酶对环氧底物进行不对称水解,然后再通过酸处理未开环的环氧化物“一锅法”高产率、高选择性的生成单一构型的手性二醇。这一新发展为这种酶在精细合成工业上的运用开辟了广阔的前景。     

The Modulation of Arachidonic Acid Metabolism and Blood Pressure-Lowering Effect of Honokiol in Spontaneously Hypertensive Rats

Background: Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Methods: Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Results: Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON. Conclusion: Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.     

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of bioactive lipid signaling molecules. The substrate-specific hydrolase activity of sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, antihypertensive, cardio-protective and organ-protective properties. Accordingly, sEH inhibition is a promising therapeutic strategy for addressing a variety of diseases. In this review, we describe small molecule architectures that have been commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation and cancer. We juxtapose commonly used synthetic scaffolds and natural products within the paradigm of a multitarget approach for addressing inflammation and inflammation induced carcinogenesis. Structural insights from the inhibitor complexes and novel strategies for development of sEH-based multitarget inhibitors are also presented. While sEH inhibition is likely to suppress inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis via increased EET concentrations. In this regard, sEH inhibitors in combination chemotherapy are described. Urea and amide-based architectures feature prominently across multitarget inhibition and combination chemotherapy applications of sEH inhibitors.     

Synthesis of 1,3-Disubstituted Ureas Containing Cycloheptyl or Bicyclo[2.2.1]heptyl Fragments,as Soluble Epoxide Hydrolase Inhibitors

Russian Journal of Organic Chemistry - To assess the effect of the lipophilicity of different parts of urea molecules on their activity as soluble epoxide hydrolase inhibitors, a series of...     

Synthesis and Properties of <Emphasis Type="Italic">N</Emphasis>-[R-Adamantan-1(2)-yl]-<Emphasis Type="Italic">N</Emphasis>′-(2-fluorophenyl)ureas—Target-Oriented Soluble Epoxide Hydrolase Inhibitors

2-Fluorophenyl isocyanate reacted with adamantan-1(2)-amines and their homologs in DMF to give 31–92% of the corresponding N,N′-disubstituted ureas that are target-oriented human soluble epoxide hydrolase (sEH) inhibitors. Introduction of a fluorine atom increases the sEH inhibitory activity by a factor of 4.5.     

Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase

The complete reaction mechanism of soluble epoxide hydrolase (sEH) has been investigated by using the B3LYP density functional theory method. Epoxide hydrolases catalyze the conversion of epoxides to their corresponding vicinal diols. In our theoretical study, the sEH active site is represented by quantum-chemical models that are based on the X-ray crystal structure of human soluble epoxide hydrolase. The trans-substituted epoxide (1S,2S)-beta-methylstyrene oxide has been used as a substrate in the theoretical investigation of the sEH reaction mechanism. Both the alkylation and the hydrolytic half-reactions have been studied in detail. We present the energetics of the reaction mechanism as well as the optimized intermediates and transition-state structures. Full potential energy curves for the reactions involving nucleophilic attack at either the benzylic or the homo-benzylic carbon atom of (1S,2S)-beta-methylstyrene oxide have been computed. The regioselectivity of epoxide opening has been addressed for the two substrates (1S,2S)-beta-methylstyrene oxide and (S)-styrene oxide.     

Prospects for the inhibition of the phosphatase domain of human soluble epoxide hydrolase (sEH-P)

Russian Chemical Bulletin - This brief review highlights the history of the discovery of the phosphatase domain of human soluble epoxide hydrolase (sEH-P). The data on its structure and...     

Synthesis and properties of symmetrical <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>'-Bis(R-adamantan-1-yl)ureas as target-oriented soluble epoxide hydrolase (sEH) inhibitors

Self-condensation of substituted adamantan-1-yl isocyanates in THF in the presence of DBU afforded 91–96% of symmetrical ureas as target-oriented soluble epoxide hydrolase (sEH) inhibitors. The described reaction avoids the use of the corresponding amine as counterpart. The obtained ureas are characterized by reduced melting points and improved solubility in water.     

Synthesis and Properties of <Emphasis Type="Italic">N</Emphasis>-(R-Adamantan-1-ylalkyl)-<Emphasis Type="Italic">N′</Emphasis>-[3(4)-fluorophenyl]thioureas—Target-Oriented Human Soluble Epoxide Hydrolase (hsEH) Inhibitors

Reactions of 3(4)-fluorophenyl isothiocyanates with amines of the adamantane series in DMF afforded 86–93% of the corresponding N,N′-disubstituted thioureas that are target-oriented inhibitors of human soluble epoxide hydrolase (hsEH). The effect of isosteric replacement of hydrogen in the aromatic fragment by fluorine and of oxygen in the urea fragment by sulfur on the IC₅₀ value was estimated. The inhibitory activity increases twofold for the 3-fluorophenyl derivatives and ninefold for 4-fluorophenyl analogs.     

High-throughput pharmacokinetic method: cassette dosing in mice associated with minuscule serial bleedings and LC/MS/MS analysis

A method for pharmacokinetic studies using cassette dosing associated with serial bleeding in mice is described. PK profiles of four soluble epoxide hydrolase inhibitors were determined following oral, subcutaneous or intraperitoneal administration individually or in cassette dosing. Parent analyses were performed on only 5 μL of whole blood from serial bleeds (up to 10 per animal), by LC/MS/MS. An accuracy (88-100%) and precision (<10% RSD) were observed, leading to reliable datum points for PK calculation. PK profiles, T_max, C_max and half-life values after cassette dosing were similar to the individual PK results. This method dramatically increases speed of data collection while dramatically reducing cost and animal usage. The results presented here clearly indicate that this proposed method could be applicable to high-throughput PK studies.     

New aminocyclitols as modulators of glucosylceramide metabolism

A series of 13 aminocyclitol derivatives belonging to two different families is described. Their configuration is governed by the regio- and stereocontrolled epoxide opening of a suitably protected conduritol-B epoxide. Studies on several glycosyl processing enzymes indicate that some of them are good inhibitors of glucosylceramide hydrolase. A rationale to account for preliminary structure-activity relationships is provided.