(2S)-(+)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮的不对称合成

以(2R,3R)-酒石酸二甲酯为手性辅助剂,6-甲氧基-2-丙酰基萘经缩酮化、溴化铜不对称溴化、水解等反应合成了(2S)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮。总收率94%。     

6,6'-取代1,1'-联二萘酚衍生的手性磷酸的合成

1,1'-联二萘酚(1)经溴代反应制得6,6'-二溴-1,1'-联二萘酚(2);2经苄基保护羟基制得2,2'-二苄氧基-6,6'-二溴-1,1'-联二萘(3);3经Ullmann缩合在6,6'-位引入甲氧基制得2,2'-二苄氧基-6,6'-二甲氧基-1,1'-联二萘(4b);3经Kumada偶联反应在6,6'-位引入正己基制得2,2'-二苄氧基-6,6'-二正己基-1,1'-联二萘(4c);4b和4c经还原脱去苄基制得6,6'-位取代1,1'-联二萘酚(5b和5c);2,5b和5c分别与三氯氧磷反应合成了3种1的6,6'-位取代手性磷酸(6a~6c),其结构经1H NMR和31P NMR表征。其中6c为新化合物。     

联萘衍生物的磺化反应研究

研究了1-和2-苯基萘, 1, 1'-和2, 2'-联萘, 2, 2-二羟基-, 2, 2'-二甲氧基和-2, 2'-甲基磺酰氧基-1, 1'-联萘等七种萘衍生物和三氧化硫的磺化反应。1-苯基萘和1, 1'-联萘的磺化先发生在4位上, 第二取代位置为6和7位。2-苯基萘和2, 2'-联萘均首先得到8位磺酸取代物, 进一步磺化得到8, 4'-和8, 8'-二磺酸取代物。2, 2'-二甲氧基-1, 1'-联萘以13:87的比例得到3位和6位磺酸取代物。2, 2'-二甲磺酰氧基-1, 1'-联萘以58:42的比例得到5位和6位磺酸取代物。2, 2'-二羟基-1, 1'-联萘的等摩尔磺化得到比例为35:65的5位和6位磺酸取代物, 和大于6摩尔的SO~3反应则以62:38的比例得到5位和6位磺酸取代物。     

6-甲氧基-2-丙酰基萘在醇溶剂中的溴化反应

室温下，6－甲氧基－2－丙酰基萘和1，3－二溴－5，5－二甲基海因的溴化反应在醇溶剂中，反应速度快、转化率高，生成5－溴－6－甲氧基－2－丙酰基萘的收率高（98．59％）。     

非甾体消炎药萘普生不对称合成研究

萘普生[(S)-(+)-S-(6'-甲氧基-2'-萘基)丙酸]是一种非常重要的非甾体消炎镇痛药。以(2R,3R)-酒石酸二甲酯为手性辅助剂,2-甲氧基萘经溴代、丙酰化、缩酮化、不对称溴化、水解、立体专一性重排和催化氢转移氢解等反应合成了光学活性萘普生,化学收率44%。制备的萘普生的光学纯度([α]~D^2^5=+63.5ⅲ)符合中华人民共和国药典(1995年版)的要求。     

应用芳基锂合成查尔酮

苯基锂、2-甲氧基苯基锂和2,4-二甲氧基苯基锂分别与肉桂酸反应以相当好的收率生成相应的查尔酮;2,6-二甲氧基苯基锂与肉桂酸不发生反应,但能与肉桂酸甲酯反应生成2',6'-二甲氧基查尔酮;类似的还制得了2',4',6'-三甲氧基查尔酮和2',4',4,6'-四甲氧基查尔酮.2,4-二甲氧基苯基锂和2,4,6-三甲氧基苯基锂也能与γ-丁酸内酯反应分别生成γ-羟丙基-(2,4-二甲氧基苯基)酮和γ-羟丙基-(2,4,6-三甲氧基苯基)酮.没发现三级醇生成.     

手性相转移催化剂的合成及其在氨基酸烷基化反应中的应用

以2-叔丁基-5-甲基苯酚为原料,经4步反应制得2,2'-二甲基-3,3'-取代基-4,4'-二甲氧基-5,5'-二叔丁基-1,1'-联苯(6a~6g);6经溴化反应制得2,2'-二溴甲基-3,3'-取代基-4,4'-二甲氧基-5,5'-二叔丁基-1,1'-联苯(7a~7g);7与(R)-(+)-N-甲基-1-(1-萘基)乙基胺经环合反应合成了7种具有联苯结构的手性相转移催化剂(9a~9g)。6f,6g,7f,7g,9f和9g为新化合物,其结构经1H NMR,13C NMR和MS表征。以N-二苯基亚甲基甘氨酸叔丁酯的不对称烷基化为探针反应,考察了9a~9g的催化活性。结果表明:在催化剂用量为1mol%时,9g的催化性能最好,产率和对映选择性分别为80%和70%。     

5-(取代萘基)乙内酰脲的合成

在酸催化下,2－萘酚、1－溴－2羟基萘分别与尿囊素反应制得5－（2′-羟基－1′-萘基）乙内酰脲（收率81．8％）和5－（5′-溴－6′－羟基－2′－萘基）乙内酰脲（收率52．3％）。     

薄层光密度法测定低含量的N—（α—萘基）咔唑和N—（β—萘基）咔唑

测定了光诱导ＳＲＮ１反应生成的Ｎ－（α－萘基）咔唑和Ｎ－（β－萘基）。光化学反应产物用硅胶板展开，外标法定量，测定波长２８８ｎｍ斑点的线性范围０～２μｇ，回收率１００．５％，相对标准偏差４．８％，Ｎ－（α－萘基）咔唑含量＜１％，Ｎ－（β－萘基）咔唑含量２．２６％。     

薄层光密度法测定低含量的N－（α－萘基）咔唑和N－（β－萘基）咔唑

测定了光诱导ＳＲＮ１反应生成的Ｎ－（α－萘基）咔唑和Ｎ－（β－萘基）咔唑。光化学反应产物用硅胶板展开，外标法定量，测定波长２８８ｎｍ，斑点的线性范围０～２μｇ，回收率１００．５％，相对标准偏差４．８％，Ｎ－（α－萘基）咔唑含量＜１％，Ｎ－（β－萘基）咔唑含量２．２６％。     

Trichosporon beigelli esterase (TBE): a versatile esterase for the resolution of economically important racemates

A hydrolase producing strain Trichosporon beigelli esterase (TBE) isolated from local cottage cheese in its native form has displayed versatility and high efficacy in the kinetic resolution of a wide range of economically important substrates, which include racemic secondary alcohols, such as 1-(6-methoxy-2-naphthyl)ethanol (E ∼ 316), 1-(3,4-methylenedioxyphenyl)ethanol and pentanol (E ∼ 180 and 156 resp.), and alkyl esters of carboxylic acids such as ibuprofen (E ∼ 340), 2-(benzylthio)propanoic acid (E ∼ 1000). In other substrates such as in the primary alcohol 2-(6-methoxy-2-naphthyl)propan-1-ol and carboxylic acids such as 2-(5-bromo-6-methoxy-2-naphthyl)propanoic acid, 2-(2-naphthyloxy)propanoic acid, and substituted 2-thiopropanoic acids, it displayed moderate to low selectivity. Commercial lipases such as CCL, PPL, and PSL were also used in the resolution of the substrates for comparative studies.     

PVP-PdCl2-CuCl2/PPh3体系催化α-（6’-甲氧基-2’-萘基）乙醇羰化反应研究

首次用高分子负载型双金属催化剂PVP-PdCl2-CuCl2/PPh3体系催化α-（6’-甲氧基-2’-萘基）乙醇与一氧化碳及甲醇进行羰化反应制备萘普生甲酯, 分别对温度、压力、时间、 P/Pd比等影响因素进行了考察, 在反应条件为100 ℃、 16～20 h、 CO压力 4.0 MPa、 P/Pd=3时, 转化率可达97.4%, 异正比为14.4. 在同样条件下制备萘普生乙酯及萘普生异丙酯, 转化率及选择性均有明显下降. 另外, 该催化剂体系也可催化其它类型α-芳基乙醇的羰化反应.     

Separation of 4-dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine derivatives of carbonyl compounds by reversed-phase capillary electrochromatography

4-Dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine (DMNTH) is a novel derivatizing reagent specially designed for the determination of carbonyl compounds. In this work, we describe the separation of DMNTH-derivatized carbonyl compounds by reversed-phase capillary electrochromatography (CEC). After systematic investigations of the effects of experimental conditions viz. pH and concentration of buffer, type of stationary phase, injection volume of sample, organic modifier, and temperature, optimal conditions were found. The sample compounds, which were separated with gradient high performance liquid chromatography (HPLC), were separated by CEC under isocratic elution due to the high efficiency. Comparisons of separations by CEC and micellar electrokinetic chromatography (MEKC) were made.     

Influence of chiral ionic liquids on the excited-state properties of naproxen analogs

The synthesis and decolorization of chiral room-temperature ionic liquids based upon 1-methyl imidazole and chloromethyl menthyl ether is reported. The excellent optical quality of these solvents permits the investigation of the effects of the two enantiomers on the excited-state photophysics of (S)-N-methyl-2-pyrrolidinemethyl 2(S)-(6-methoxy-2-naphthyl)propionate [(S,S)-NPX-PYR]. Whereas in conventional bulk polar solvents such as acetonitrile, (S,S)-NPX-PYR is known to execute excited-state intramolecular electron transfer and to form exciplexes, in these chiral solvents these nonradiative processes are absent. The chiral solvents do, however, induce a small but reproducible (approximately 10%) stereodifferentiation in the fluorescence lifetime of (S,S)-NPX-PYR as well as in the parent compound, (S)-naproxen. To our knowledge, this is the first example of chiral ionic liquids inducing such an effect on photophysical properties.     

Simple Synthetic Approach to Arylacetic Nsaias via TosMIC Procedure

Preparation of 1-methylpyrrole-2-acetonitrile, 1-methyl-5-(4-methylbenzoyl) pyrrole-2-acetonitrile and 2-(6-methoxy-2-naphthyl)propionitrile by treatment of 1-methylpyrrole-2-carboxaldehyde, 1-methyl-5-(4-methylbenzoyl)pyrrole-2-carboxaldehyde and, respectively, 6-methoxy-2-acetylnaphthalene with tosylmethylisocyanide (TosMIC) is described. This one-step synthetic procedure is very useful to obtain the nitrile precursors of tolmetin and naproxen, two clinically important non-steroidal antiinflammatory agents (NSAIAs).     

2，6-二-O-乙氧乙基-3-O-三氟乙酰基-β-环糊精气相色谱手性固定相的制备及应用

将β-环糊精的2,6-位引入乙氧乙基,3-位引入三氟乙酰基,合成了新的环糊精衍生物2,6-二-O-乙氧乙基-3-O-三氟乙酰基-β-环糊精,并采用静态法涂渍毛细管气相色谱柱,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G rob试剂、苯的二取代位置异构体氯甲苯、硝基甲苯和溴甲苯以及10种手性化合物如α-取代丙酸酯化合物、1-(2′-硝基苯基)-乙醇、α-甲基-对氯苯乙腈和丙炔醇酮乙酸酯等具有良好的分离效果。其中,对α-甲磺酰基丙酸酯对映体的拆分效果最好;对α-取代丙酸的甲酯衍生物的分离效果优于乙酯衍生物;对α-羟基取代丙酸酯的分离效果优于α-卤代丙酸酯。     

二乙二醇丙酸甲酯的合成与结构表征

采用二乙二醇和丙酸甲酯为主要原料,以钾为催化剂,在通N_2气保护的条件下合成二乙二醇丙酸甲酯,用离子排阻高效液相色谱法对合成的二乙二醇丙酸甲酯进行定量分析。最佳合成条件:二乙二醇与丙酸甲酯的物质的量比为1∶2,催化剂的质量为反应物二乙二醇质量的1.5%,于25℃条件下反应24 h,产物经硅胶柱分离、乙酸乙酯梯度洗脱,然后干燥,制得二乙二醇丙酸甲酯成品,收率为61.5%,纯度达99.5%。用FT-IR,~1H–NMR,GC–MS法对二乙二醇丙酸甲酯的分子结构进行了确证。     

On-line high performance liquid chromatography — multidimensional gas chromatography and its application to the determination of stilbene hormones in corned beef

The combination of high performance liquid chromatography interfaced on-line with multidimensional gas chromatography (HPLC–GC–GC) is described. The HPLC column was interfaced to the GC via an on column interface, with automated pneumatic control of solvent evaporation and GC column switching. Cryogenic cold trapping was used for analyte focusing at the head of the first, non-polar GC capillary column and optionally at the head of the second, polar column. The determination of stilbene hormones in corned beef as their methylated derivatives by flame ionization detection is described.     

A possible ethanol-catalyzed rearrangement of vitamin K(1) detected by gas chromatography/mass spectrometry

We studied vitamin K(1)(20), vitamin K(1)(25), and vitamin K(1) epoxide in n-hexane and ethanol solutions by gas chromatography/mass spectrometry (GC/MS) utilizing a DB-5 MS fused-silica capillary column. In ethanol solutions of K(1), we observed an extra peak eluting from the GC column with somewhat longer retention time than K(1)(20). A similar peak following K(1)(25) was also found. These peaks were not found in n-hexane solutions of K(1). A close examination of the mass spectra of these peaks indicated that they were vitamin K(1) variants containing a base peak at m/z 225 characteristic of the methylnaphthoquinone ring with a four-carbon side chain. In addition, they contained the molecular ions of K(1)(20) and K(1)(25), respectively. We conclude that K(1)(20) and K(1)(25), but not K(1) epoxide, might undergo rearrangements in ethanol involving an intramolecular proton transfer and a shift of the beta,gamma-double bond on the phytyl side chain toward the ring. The conjugation of the phytyl double bond with the quinone ring is probably the driving force of the rearrangement. We emphasize, however, that our conclusion is based only on mass spectral analysis and would require further investigation by other spectroscopic methods.     

Determination of residual solvents and reagents in X-ray contrast media by automatic static headspace capillary gas chromatography

A specific, sensitive, and simple method for the quantitation of residual methanol, 2-propanol, 2-butanol, 2-methoxy-1-ethanol, 1-chloro-3-methoxy-2-propanol, 3-chloro-2-methoxy-1-propanol, and 1,3-dimethoxy-2-propanol in two non-ionic X-ray contrast media, has been developed. The headspace of a 25 % w/V aqueous solution of contrast media, obtained at 90–110°C in 15 min, was injected onto a capillary column coated with cyanopropyl, phenyl, dimethylpolysiloxane polymer. The internal standards used were 2-pentanol and 3-methoxy-1-butanol. The limits of detection were below 5 μg/g. The repeatability of the method at 50 μg/g of each solvent was below 5 %; and at 100 μg/g of the methoxypropanol compounds and 2-methoxy-1-ethanol, below 10 % (RSD, N = 5).