(S)-美托洛尔的不对称合成

用自制的(S,S)-Salen Co(Ⅲ)OAc催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯的(S)-3-氯-1,2-丙二醇和较高光学纯的(R)-环氧氯丙烷。 以(S)-3氯-1,2-丙二醇为手性原料和4-(2-甲氧基乙基)苯酚缩合,再与氯化亚砜反应得环状亚硫酸酯,最后和异丙胺反应得(S)-美托洛尔,光学纯度大于99%。 另外以(R)-环氧氯丙烷为手性原料和4-(2-甲氧基乙基)苯酚反应,再与异丙胺作用得到(S)-美托洛尔,光学纯度大于92%。 (S)-美托洛尔的总收率为53.9%,结构经IR、1H NMR、13C NMR和MS测试技术确证。 该路线原料利用率高,拆分后的2种产物均能用于目标化合物的合成。     

有机溶剂/缓冲液两相体系中全细胞催化拆分环氧氯丙烷

研究了有机溶剂/缓冲液两相体系中重组大肠杆菌E.coli BL21 (DE3)全细胞水解动力学拆分外消旋环氧氯丙烷制备(R)-环氧氯丙烷的过程.结果表明,最适反应条件为:最适有机溶剂异辛烷与缓冲液的体积比7:3,最适缓冲液pH 8.0,底物浓度574mmol/L,全细胞加入量0.07g湿菌体/ml溶液,温度30℃.在此条件下于1L反应器中反应45min,(R)-环氧氯丙烷的摩尔产率、光学纯度和时空产率分别达到37.5%,99.3%ee和0.286mol/(L·h).与单一水相体系相比,异辛烷/缓冲液两相体系中底物浓度和(R)-环氧氯丙烷时空产率分别提高了55.2%和98.6%.     

1,2-环氧丙醚基芳香酮紫外线吸收剂的微波合成和表征

以2,4-二羟基二苯甲酮、4-羟基苯乙酮(HAP)为原料分别和环氧氯丙烷反应,经微波辐照合成了两种反应性紫外线吸收剂2-羟基-4-缩水甘油醚基二苯甲酮(HEPBP)和4-缩水甘油醚基苯乙酮(EPAP)。结构采用红外光谱、核磁和质谱表征。最佳合成条件为:n(羟基芳香酮)∶n(环氧氯丙烷)=1∶3,微波功率400W,于90℃反应15min,收率分别是52.6%和58.3%。与常规合成方法比较,微波合成法能降低反应温度、大大地缩短反应时间。产物中环氧丙烷基团的引入能明显改善芳香酮类紫外线吸收剂的紫外吸收性能。     

环氧氯丙烷类阳离子改性絮凝剂的合成及性能研究

为提高环氧氯丙烷胺类絮凝剂的絮凝性能,选用六次甲基四胺为交联剂,以环氧氯丙烷、二甲胺为主要原料,合成了环氧氯丙烷-二甲胺-六次甲基四胺(HMTA)季铵盐阳离子改性絮凝剂,其在辽河油田废水处理中表现出优异的絮凝性能,并研究了絮凝剂用量和温度对HMTA絮凝剂絮凝性能的影响。结果表明,使用HMTA絮凝剂的合适温度为45℃,最佳用量为20mg/L,除浊率可达98. 1%,除油率达到35. 1%。红外光谱和核磁共振谱的表征结果证实六次甲基四胺在聚合物中发挥了交联剂的作用,有效提高了环氧氯丙烷胺类絮凝剂的絮凝性能。     

酶法合成3-氯-1,2-丙二醇棕榈酸二酯-D5的研究

以环氧氯丙烷-D_5为起始原料,经水解反应得到3-氯-1,2-丙二醇-D_5,然后和棕榈酰氯在固定化脂肪酶催化下得到稳定同位素标记的3-氯-1,2-丙二醇棕榈酸二酯-D_5。以消耗的环氧氯丙烷-D_5计算,3-氯-1,2-丙二醇棕榈酸二酯-D_5的总产率为52.4%。产品结构、纯度和氘同位素丰度经核磁共振波谱(NMR)、高效液相色谱(HPLC)和质谱(MS)等仪器表征确定,3-氯-1,2-丙二醇棕榈酸二酯-D_5的色谱纯度和氘同位素丰度均高于99.0%。该化合物可以作为稳定同位素内标试剂,用于油脂中3-氯-1,2-丙二醇棕榈酸二酯的含量检测。     

(S)-和(R)-普萘洛尔的不对称合成

普萘洛尔是一种临床上广泛使用的β受体阻断剂, 介绍了一种不对称合成(S)-和(R)-普萘洛尔的方法. 以手性Salen-Co^III催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯度的(S)-环氧氯丙烷和(R)-3-氯-1,2-丙二醇, 以(S)-环氧氯丙烷为手性原料先水解得(S)-3-氯-1,2-丙二醇, 其与1-萘酚反应得(S)-3-(1-萘基)-丙烷-1,2-二醇, 再与氯化亚砜反应得环状亚硫酸酯, 最后和异丙胺作用得(S)-普萘洛尔, 总收率80.9%, 光学纯度大于99%; 而同样以(S)-环氧氯丙烷为手性原料直接与1-萘酚反应得(2R)-3-(1-萘氧基)-1,2-环氧丙烷, 再与异丙胺作用得(R)-普萘洛尔, 总收率74.5%, 光学纯度大于99%.     

气相色谱法分析阳离子醚化剂中残存的环氧氯丙烷和1,3-二氯丙醇

建立了液体阳离子醚化剂中残存的环氧氯丙烷、1,3-二氯丙醇的气相色谱分析法。用苯甲酸甲酯萃取样品,对两组分都有很高的萃取率。选用HP-5 30　m毛细管柱,一次进样能同时测定两组分,两组分达到完全分离,且均在萃取剂前出峰,因而减少了峰扩散,提高了检测灵敏度。检测的线性范围:环氧氯丙烷5～590 mg/kg,1,3-二氯丙醇21～480 mg/kg;检测限:环氧氯丙烷1.2 mg/kg,1,3-二氯丙醇2.2 mg/kg;回收率：环氧氯丙烷95.93%～103.42%,相对标准偏差(RSD)2.4%～10.     

改性果胶-Fe_3O_4磁性微球的制备及对Cu~(2+)吸附性能研究

采用氯化钙、环氧氯丙烷交联改性,制备了改性果胶磁性微粒,分别用红外光谱、扫描电镜、X-射线衍射对样品进行了表征并对实验条件进行了探究。实验结果表明:环氧氯丙烷改性果胶-Fe_3O_4微球吸附剂对Cu~(2+)有较好的吸附。该吸附符合准二级动力学方程,主要为化学吸附。当Cu~(2+)的初始浓度160 mg·L~(-1),吸附剂添加量为20 mg,反应时间为90 min,反应温度为60℃时的单位吸附量为74.89 mg·g~(-1)。研究还表明EDTA对磁性微球的洗脱效果最佳。环氧氯丙烷改性果胶-Fe_3O_4微球吸附剂对香螺、海螺和黄蚬子三种贝类的酶解液中Cu~(2+)进行脱除实验,去除率分别为85.1%,82.4%和83.5%,效果良好。     

气相色谱-质谱法测定乙二醇二缩水甘油醚中环氧氯丙烷的残留量北大核心CSCD

提出了气相色谱-质谱法测定乙二醇二缩水甘油醚中环氧氯丙烷残留量的方法。样品5.000 0 g置于10 mL容量瓶中,用乙醇稀释并定容。所得溶液经超声处理后,采用HP-5MS毛细管柱、载气程序升流和柱程序升温进行气相色谱分离。质谱分析中采用电子轰击离子源和选择离子监测模式。环氧氯丙烷的质量浓度在12.06~602.97 mg·L^(-1)范围内与其峰面积呈线性关系,测定下限(10S/N)为4.21 mg·L^(-1),测定值的相对标准偏差(n=8)为0.51%。按标准加入法进行回收试验,回收率在94.2%~97.1%之间。     

气相色谱-质谱法测定乙二醇二缩水甘油醚中环氧氯丙烷的残留量

提出了气相色谱-质谱法测定乙二醇二缩水甘油醚中环氧氯丙烷残留量的方法。样品5.000 0 g置于10 mL容量瓶中,用乙醇稀释并定容。所得溶液经超声处理后,采用HP-5MS毛细管柱、载气程序升流和柱程序升温进行气相色谱分离。质谱分析中采用电子轰击离子源和选择离子监测模式。环氧氯丙烷的质量浓度在12.06~602.97 mg·L~(-1)范围内与其峰面积呈线性关系,测定下限(10S/N)为4.21 mg·L~(-1),测定值的相对标准偏差(n=8)为0.51%。按标准加入法进行回收试验,回收率在94.2%~97.1%之间。     

Asymmetric Synthesis of (R)-and (S)-Moprolol

A simple and effective procedure for the enantioselective synthesis of (R)-and (S)-moprolol was described.The key step was the asymmetric synthesis of enantiopure (R)-and (S)-guaifenesin,which were synthesized from enantioenriched (R)-3-chloro-1,2-propanediol and (S)-epichlorohydrin via kinetics of hydrolysis resolution of racemic epichlorohydrin by chiral Salen-CoIIII complex.The e.e.values of both the optical compounds were above 98%,and the chemical structures of the target compounds were confirmed by 1H NMR,13C NMR,IR,and MS.     

三七素手性拆分方法的研究

使用气相色谱法和高效液相色谱法分离了三七素对映体,并探讨了影响液相色谱法分离效果的因素。结果表明,HPLC法利用手性固定相进行直接拆分,无法实现对映体的完全分离;GC法和HPLC的手性试剂衍生化法均可对三七素对映体进行较好的分离。但GC法由于衍生化过程中副产物的存在,干扰了对映体的准确定量。手性试剂衍生化HPLC法,以邻苯二甲醛、N-酰化-L-半胱氨酸为衍生化试剂,反应得到的三七素对映体的衍生物在ODS柱上分离良好,且方法简单、快速。     

七(2,3,6-三-O-甲氧甲基)-β-环糊精的合成及其在气相色谱分离中的应用

将甲氧甲基引入β-环糊精的2,3,6-位合成了新的气相色谱手性固定相七(2,3,6-三-O-甲氧甲基)-β-环糊精,并采用静态法将其涂渍在毛细管内壁制备毛细管气相色谱柱。考察了毛细管柱的柱性能和分离性能。结果表明该固定相对Grob试剂、苯的二取代位置异构体(硝基甲苯、溴甲苯、二氯苯和二甲苯)及手性化合物(2-羟基丙酸甲酯、2-羟基丙酸乙酯和2-甲磺酰基丙酸甲酯)都具有良好的分离效果。与固定相2,3,6-三-O-甲基-β-环糊精的手性分离效果对比,结果显示两种手性固定相的分离能力各异,对一些手性脂类化合物对映体的分离存在互补性。     

Development of versatile cis- and trans-dicarbon-substituted chiral cyclopropane units: synthesis of (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclopropanes and their enantiomers as conformationally restricted analogues of histamine

The cyclopropane ring can be used effectively in restricting the conformation of biologically active compounds to improve activity and also to investigate bioactive conformations. We designed (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclopropanes (1 and 2, respectively) and their enantiomers (ent-1 and ent-2) as conformationally restricted analogues of histamine. The four types of chiral cyclopropanes bearing two differentially functionalized carbon substituents in a cis or trans relationship on a cyclopropane ring, (1S,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (7) and (1R,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (8) and their enantiomers (ent-7 and ent-8), were developed as the key intermediates for synthesizing 1, 2, ent-1, and ent-2. The reaction between (R)-epichlorohydrin [(R)-12] and phenylsulfonylacetonitrile (13a) in the presence of NaOEt in EtOH followed by treatment with acid gave the chiral cyclopropane lactone 11a with 98% ee in 82% yield. Compound 11a was converted into both the cis- and trans-chiral cyclopropane units 7 and 8, respectively, via reductive desulfonylation with Mg/MeOH as the key step. The corresponding enantiomers, the cis-substituted ent-7 and the trans-substituted ent-8, were also prepared starting from (S)-epichlorohydrin [(S)-12]. The four conformationally restricted target histamine analogues 1, 2, ent-1, and ent-2 were successfully synthesized from 7, 8, ent-7, and ent-8, respectively. The chiral cyclopropane units 7, 8, ent-7, and ent-8 should be useful as versatile intermediates for synthesizing various compounds having an asymmetric cyclopropane structure.     

Synthesis of conformationally restricted analogs of baclofen, a potent GABAB receptor agonist, by the introduction of a cyclopropane ring.

Conformationally restricted analogs of baclofen (2), i.e., 5, 6, and their enantiomers ent-5, and ent-6, the conformations of which were restricted by introducing a cyclopropane ring, were designed as potential GABAB receptor ligands. Reaction of (R)-epichlorohydrin [(R)-7] and (4-chlorophenyl)acetonitrile in the presence of NaNH2 in benzene/tetrahydrofuran gave chiral cyclopropane derivatives 11 and 12, which were then converted into the target compounds 5 and 6, respectively. Their corresponding enantiomers, ent-5 and ent-6, were also synthesized starting from (S)-epichlorohydrin [(S)-7].     

Hybridation of different chiral separation techniques with ICP-MS detection for the separation and determination of selenomethionine enantiomers: chiral speciation of selenized yeast

Enantioseparation and determination of selenomethionine enantiomers in selenized yeast was investigated using chiral separation techniques based on different principles, coupled on-line to inductively coupled plasma mass spectrometry (ICP-MS) for selenium-specific detection. High performance liquid chromatography (HPLC) on a beta-cyclodestrin (beta-CD) column, cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC), gas chromatography (GC) on a Chirasil-L-Val column, and HPLC on a Chirobiotic T column have been investigated as the chiral separation techniques. For HPLC separation on the beta-CD column, and also for CD-MEKC, selenomethionine enantiomers were derivatized with NDA/CN(-). For chiral separation by GC, selenomethionine enantiomers were converted into their N-trifluoroacetyl (TFA)-O-alkyl esters. The developed hybridation methodologies are compared with respect to enantioselectivity, sensitivity and analysis time. The usefulness of the best-suited method [HPLC (Chirobiotic T)-ICP-MS] was demonstrated by its application to the successful chiral speciation of selenium and D-and L-selenomethionine content determination in selenized yeast.     

Chiral discrimination of limonene by use of beta-cyclodextrin-coated quartz-crystal-microbalances (QCMs) and data evaluation by artificial neuronal networks

The enantiomeric composition of the chiral flavoring agent limonene was analyzed by means of a quartz-crystal microbalance (QCM) sensor. As chiral selectors three different modified beta-cyclodextrins were investigated. The selector molecules were applied as mixtures in different polysiloxane matrices. The chiral separation factors alpha for limonene obtained at 30 degrees C by gas chromatography and by use of the QCM sensor were comparable. Evaluation of sensor data was performed by use of an artificial neuronal network (ANN); this enabled prediction of the enantiomeric composition of the gas mixtures.     

Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography coupled to evaporative light scattering detection

A method for the separation and quantitation of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography and evaporative light scattering detection has been developed. Separation of the enantiomers was performed in normal-phase liquid chromatography on a Chiralpak AS chiral stationary phase. The influence of the gas nature, gas pressure and temperature of the drift tube of the evaporative light scattering detector on the detection sensitivity was investigated. The method was validated in terms of linearity, limit of quantitation, accuracy and precision. The enantiomeric excess of (S)-3-tert.-butylamino-1,2-propanediol, used for the industrial synthesis of (S)-timolol, was measured from 0 to 94%.