鼠血中烯丙洛尔对映体的毛细管电泳分离与测定

建立了一种双手性拆分试剂(羟丙基-β-环糊精和羧甲基-β-环糊精)拆分烯丙洛尔对映体的毛细管电泳方法。烯丙洛尔对映体在pH 3.8的80 mmol/L Tris-H3PO4+15 mmol/L羟丙基-β-环糊精(HP--βCD)+5.0 g/L羧甲基-β-环糊精(CM--βCD)条件下获得成功分离。以(1R,2R)-2-氨基-1-苯基-1,3-丙二醇为内标,采用内标法定量,烯丙洛尔对映体在0.25~50 mg/L范围内具有良好线性关系,检出限(S/N=3)为0.25 mg/L,日内、日间RSD均不大于6%,平均回收率为97%~102%。该方法可用于鼠体内烯丙洛尔的药代动力学研究。     

环糊精固定相-电化学检测测定肾上腺素和拟肾上腺素对映体

以乙酰化-β-环糊精作固定相,较系统地研究了流动相组成及柱温、流速等对肾上腺素类对映体分离的影响,优化了的反相色谱流动相组成为0.06mo1/L NaOAC(pH 5.0)+0.03mmol/L EDTA@2Na+2(vol)%CH3CN,工作电位E为+0.60V.探讨了环糊精立体选择性与主-客体分子结构之间的关系.工作曲线的线性范围0～250μg/L,检测限低于0.60ng/L,相对标准偏差小于3.5%.     

苯氨基甲酸酯化β-环糊精手性固定相测定中草药中柚皮甙对映体

采用自制的苯氨基甲酸酯衍生化β-环糊精键合SBA-15手性固定相,以甲醇-水作流动相,拆分了柚皮甙对映体;考察了流动相组成、柱温、检测波长等对柚皮甙拆分和测定的影响,优化的色谱条件为:流动相为甲醇-水(55:45,V/V),流速0.5 m L/min,柱温20℃,进样量10μL,检测波长为285 nm。基于上述条件,对中草药化橘红、香橼、枳壳及柚皮中的柚皮甙对映体进行了含量测定。柚皮甙每个对映异构体均在0.5~500μg/m L范围内线性关系良好(r≥0.995),检出限为0.04μg/m L(S/N=3)。以化橘红为例,柚皮甙第一个对映体的加标平均回收率为93.8%和RSD为1.2%(n=5),第二个对映体的加标平均回收率为91.3%和RSD为1.6%(n=5)。测得化橘红、香橼、枳壳和柚皮中柚皮甙两对映体的含量分别为10.42 mg/g和15.84 mg/g,15.39 mg/g和49.52 mg/g,16.53 mg/g和95.80 mg/g,18.47 mg/g和30.98 mg/g。     

橙汁类饮料中橙皮苷、柚皮苷含量的测定

建立了反相高效液相色谱法测定橙汁中橙皮苷和柚皮苷的方法,并对不同厂家生产的橙汁饮料中橙皮苷和柚皮苷进行了比较.采用SHIMADZUVPODS(4.6 mm×150 nn,5μm)色谱柱;V(乙腈):V(磷酸水溶液)=22:78(pH 3.5)为流动相,流速为1.2 Ml/min;检测波长为283 nm.结果待测组分与其他组分分离度良好(>1.5),橙皮苷和柚皮苷线性范围分别为2.8～56.0 μg/mL和0.43～8.6μg/mL,橙皮苷和柚皮苷的平均回收率分别为99.9%,98.9%,RsD分别为1.9%,1.3%.     

固相萃取-毛细管电泳法测定免血清中的山茛菪碱对映体

建立一种可用于定量的毛细管电泳法分离山莨菪碱对映体.系统研究了三种手性选择剂:羟丙基-β-环糊精(HP-β-CD),甲基-β-环糊精(Me-β-CD),羧甲基-β-环糊精(CM-β-CD)及其浓度、缓冲溶液浓度和pH对山莨菪碱拆分的影响.在110 mmol/L Tris-H3PO4缓冲液中加入20.0 mg/mL HP-β-CD和5.0 mg/mL CM-β-CD(pH 4.0)条件下,山莨菪碱的4个对映体达到基线分离.血清样品通过崮相萃取预处理和浓缩,对映体的固相萃取回收率在82.9%～90.7%,相对标准偏差RSD%均小于7%.山莨菪碱的4个对映体血标准溶液浓度与电泳峰面积在77.86～0.39μg/mL范围内呈良好的线,r≥0.999,检出限(S/N=3)为0.08 μg/mL.平均日内和日间精密度(RSD%)分别小于4.2%和6.5%,方法回收率为95.1%和105%.建立的方法准确、可靠,应用于监测兔连续3 d口服75 mg山莨菪碱后血清中山莨菪碱的血药浓度,结果满意.     

生物转化体系中R-肾上腺素光学纯度的测定

以羟丙基-β-环糊精(HP-β-CD)为手性选择剂,采用高效毛细管电泳技术,对肾上腺素对映体拆分进行了研究。以55mmol/LTris-磷酸(含30g/LHP-β-CD,pH2.5)为运行缓冲液,分离电压23kV,柱温22℃,采用压力正极进样(3kPa×4s),肾上腺素对映体于13min内获得良好分离(RS=2.12)。在波长214nm处进行紫外检测,迁移时间和峰面积的相对标准偏差≤3.7%,峰面积与S-肾上腺素含量在0.3～130μg/L范围内呈良好的线性关系(相关系数为0.9951),回收率在97.5%～102.5%之间,肾上腺素对映体检出限(S/N=3)可达0.1μg/L,将其应用于手性生物转化样品分析,可很好地检测出R-肾上腺素的光学纯度。本研究为该类药物的生物不对称转化提供了很好的分析方法。     

毛细管电泳法和高效液相色谱法拆分联萘二酚酸对映体

采用毛细管电泳法和高效液相色谱法直接拆分2,2′-二羟基-1,1′-联二萘-3,3′-二甲酸(HBNC)对映体.以四种不同的β-环糊精为手性添加剂,考察环糊精的种类与浓度、缓冲液pH值及浓度、分离电压、温度等因素对HBNC分离的影响.结果表明:采用10 mmol/L磺丁基醚-β-环糊精+20 mmol/L磷酸盐缓冲液(pH=7.0),20 kV分离电压,HBNC对映体在20 min内达到基线分离,分离度达到3.31.采用(S)-叔-亮氨酸基-(S)-1-(α-萘基)乙胺手性柱,正己烷-乙醇-三氟乙酸(97∶3∶0.2,V/V)流动相,HBNC对映体在40 min内也基本达到基线分离.     

氰基柱上手性流动相添加剂法拆分4-氯扁桃酸

用羟丙基-β-环糊精(HP-β-CD)作为手性流动相添加剂,在UFCN(220×4.6 mm×5μm)氰基柱上通过反相高效液相色谱实现了4-氯扁桃酸(4-Cl MA)对映体的拆分。考察了水相HP-β-CD浓度,NaH_2PO_4浓度,p H,流动相中甲醇的比例及柱温等因素对分离度的影响。确定的最优色谱条件为:水相(5 mmol/L HP-β-CD,8 mmol/L NaH_2PO_4,p H 2.8),V水相/V甲醇=95:5,柱温25℃,流速1 m L/min。此条件下4-Cl M A对映体的分离度可达1.80。同时在此色谱条件下考察了3-氯扁桃酸(3-Cl MA),2-氯扁桃酸(2-Cl MA)与扁桃酸(MA)对映体的色谱拆分结果。结果发现在此条件下,3-Cl M A对映体分离度为1.51,而2-Cl M A与M A完全没有分开。对方法进行了验证,(S),(R)-4-Cl MA两对映体低、中、高浓度日内和日间精密度的RSD均小于1.1%;(S),(R)-4-Cl M A两对映体回收率分别为101.0%和100.6%;(S),(R)-4-Cl M A两对映体检出限与定量限分别为0.028,0.030 mg/L与0.093,0.098 mg/L。     

磺丁基醚-β-环糊精手性流动相添加剂法拆分佐匹克隆对映体

采用磺丁基醚-β-环糊精(SBE-β-CD)为手性流动相添加剂,建立了反相高效液相色谱手性流动相添加剂法拆分分离佐匹克隆对映体的方法。在普通C18色谱柱(250 mm×4.6 mm×5.0μm)上,考察了水相pH、磺丁基醚-β-环糊精浓度、磷酸盐缓冲液浓度、甲醇含量、柱温等对佐匹克隆对映体拆分效果的影响。确定最适用的色谱条件:流动相为水相(5 mmol/L NaH2PO4,含磺丁基醚-β-环糊精5 mmo/L,以H3PO4调pH为3):甲醇=78:22(V/V),检测波长305nm,流速为1 mL/min,柱温为30℃,此条件下佐匹克隆对映体的保留时间分别为23.0和25.6 min,分离度为1.81。两对对映体质量浓度在0.04~0.36g/L范围内线性关系良好(r≥0.9990),保留时间的RSD分别为0.73%和0.80%,峰面积的RSD分别为1.2%和1.1%。     

TLC-HPLC-Q-TOF-MS法快速鉴定柑橘提取物消毒液中桔皮素、蜜橘黄素、新橙皮苷和柚皮苷及其含量测定

建立了薄层色谱-高效液相色谱-四极杆飞行时间质谱法联用技术(TLC-HPLC-QTOF-MS)快速鉴定柑橘提取物消毒液中桔皮素、蜜橘黄素、新橙皮苷和柚皮苷4种活性物质并测定其含量的方法。样品经氯仿-丙酮洗脱剂梯度洗脱,TLC检识,半制备HPLC纯化,HPLCMS/MS鉴定及HPLC含量测定。结果表明,以氯仿-丙酮(3:1,V/V)作为展开剂分离效果最好。以甲醇-水(7:3,V/V)作为流动相测定桔皮素和蜜橘黄素的含量,以甲醇-0.2%乙酸(13:7,V/V)作为流动相对柚皮苷和新橙皮苷进行定性和定量分析,分离度及峰形最佳。方法测定桔皮素、蜜橘黄素、新橙皮苷和柚皮苷含量的相关系数均大于0.999,检测限分别为:0.3,0.1,0.4,1.2μg/mL,相对标准偏差分别为1.9%,1.9%,2.2%,1.5%,平均回收率分别为97.0%,103.5%,97.8%,100.1%。方法可用于柑橘提取物消毒液质量控制。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.     

Knoevenagel condensation catalyzed by novel Nmm-based ionic liquids in water

A series of novel N-methyl morpholine (Nmm) based ionic liquids with 1,2-propanediol group were synthesized and used as catalysts for Knoevenagel condensation at room temperature in water. Under the effect of the catalyst, various aldehydes or aliphatic ketones could react with a wide range of activated methylene compounds well, including malononitrile, alkyl cyanoacetate, cyanoacetamide, β-diketone, barbituric acid, 2-arylacetonitrile and thiazolidinedione. Furthermore, most of the products could be separated just by filtrating and washing with water. Additionally, the catalyst is recyclable and applicable for the large-scale synthesis.     

Construction of polyheterocyclic spirotetrahydrothiophene derivatives via sulfa-Michael/aldol cascade reaction

A series of polyheterocyclic spirotetrahydrothiophene derivatives were obtained in moderate to excellent yields via a catalyst-free sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 under mild conditions. We also present the first asymmetric sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 with moderate to good enantioselectivities catalyzed by readily available chiral phase-transfer catalysts (PTCs).     

Suzuki-Miyaura reactions of the soluble guanylate cyclase inhibitor NS2028: a non-product specific route to C-8 substituted analogues

Both soluble guanylate cyclase (sGC) inhibitors ODQ 1 and NS2028 2 are synthesized via improved protocols. In the former case treating 3,4-dihydroquinoxalin-2(1H)-one oxime 8, which can be prepared in two steps from 1,2-benzenediamine, with 1,1′-carbonyldiimidazole (CDI) gives the dihydro-ODQ 10 that in the presence of KMnO₄ oxidises to give ODQ 1 in an overall yield of 46% starting from 1,2-benzenediamine. In the latter case, the synthesis affords NS2028 2 from 2-amino-4-bromophenol 3 in three steps with an overall yield of 85% and avoids the need for chromatography. Furthermore, Suzuki-Miyaura reaction conditions are described that enable the preparation of 8-aryl and 8-heteroaryl derivatives of NS2028 directly from NS2028 2. Finally, demethylation of the 8-(methoxyphenyl) substituted analogues afforded the 8-(hydroxyphenyl) derivatives 40-42. All new products are fully characterised.