2,3-二氯苯甲酸的合成新方法

探索了一条合成抗癫痫药拉莫三嗪(Lamotrig-ine)的关键中间体2,3-二氯苯甲酸的新路线.以邻氯苯胺为原料,与水合三氯乙醛、盐酸羟胺反应先制得邻氯基(N-肟基乙酰)苯胺,用浓硫酸关环生成3-氯靛红.再用过氧化氢氧化,制得2-氨基-3-氯苯甲酸;然后再经过酯化、重氮化、Sandmeyer氯代和水解,得到了目标产物2,3-二氯苯甲酸,反应总收率为49%.其结构经1H NMR、13C NMR和IR表征.

2,3-二氯苯甲酸的合成研究

2,3-二氯苯甲酸是合成特效抗癫痫药拉莫三嗪及其它治疗中枢神经紊乱药物的重要中间体。笔者用2,3-二氯苯胺经重氮化、迈尔瓦音反应制得2,3-二氯苯甲醛,再经高锰酸钾氧化制得2,3-二氯苯甲酸,总收率45%。对各步反应的操作及产品的纯化方法进行了研究。

Synthesis, Crystal Structure and Properties of a New Zn(II) Coordination Polymer Constructed from 2,3-Pyridine Dicarboxylic Acid and 1,1′-(1,4-Butanediyl)bis(imidazole)

A new coordination polymer, namely [Zn（pdc）（bbi）]n {H2 pdc = 2,3-pyridine dicar- boxylic acid, bbi = 1,1-（1,4-butanediyl）bis（imidazole）}, has been prepared under hydrothermal conditions and characterized by elemental analysis, IR, and single-crystal X-ray diffraction. It crystallizes in monoclinic, space group P21 /n with a = 8.436（3）, b = 16.988（5）, c = 12.106（4）, β = 92.204（5）°, V = 1733.6（9）3, Z = 4, C17 H17 N5 O4 Zn, Mr = 420.73, Dc = 1.612 g/cm3, F（000） = 864, μ（MoKa） = 0.452 mm-1, the R = 0.0672 and wR = 0.1645. In the mononuclear complex, each Zn（II） is five-coordinated by one carboxylate O and one pyridyl N atoms from one pdc anion, one carboxylate O atom from another pdc anion, and two N atoms from two bib ligands. The Zn（II） ions are connected by pdc ligands to form skeleton chains, and bbi ligands further link them to construct a 2D framework. The thermal and luminescence properties of the complex were also investigated.

2,3-二氯苯甲酸的合成

2,3-Dichlorobenzoic acid was prepared from 2,3-dichloroaniline by diazotization and Sandmeyerreaction to give 2,3-dichlorobenzonitrile and followed by hydrolysis with an overall yield of 58%.

SYNTHESIS AND CATIONIC RING-OPENING POLYMERIZATION OF 1, 4-ANHYDRO-2, 3-DI-O-(P-AZIDOBENZYL)-α-D-RIBOPYRANOSE

New highly stereoregular 2, 3 -di- O-(p-azidobenzyl )-(1 →5 ) - α-D -ribofuranan was synthesized byselective ring-opening polymerization of 1, 4-anhydro-2, 3 - di-O -(p-azidobenzyl )-α-D -ribopyranose(ADABR) using phosphorus pentafluoride or tin tetrachloride as catalyst at low temperature indichloromethane. The monomer was obtained by the reaction of p - bromomethyl -phenyleneazide with 1, 4 -anhydro-α-D-ribose in DMF. The structure of poly(ADANR) was identified by specific rotation and ^(13)C-NMR spectroscopy. Acid chloride-AgCl_4 complex catalyst such as CH_2=C(CH_3)C^+OClO_4^- used in thepolymerization resulted in polymers with mixed structures, i.e. (1→5)-α-D-ribofuranosidic and (1→4)-β-D-ribopyranosidic units. However, with C_6H_5C^+OClO_4^- as catalyst, pure (1→5)-α-D-ribofuranan was obtained.The effects of catalyst, polymerization temperature and time on polymer stereoregularity were examined, andthe mechanism of the ring-opening polymerization was discussed.

黄连中1个新型生物碱的研究

目的 研究黄连Coptis chinensis Franch中1个新型生物碱。方法 黄连75%乙醇提取物采用硅胶、ODS、semi-pre HPLC进行分离纯化,根据理化性质及波谱数据对鉴定所得化合物的结构。结果 从中分离得到3个化合物,分别鉴定为6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxybenzoic acid ethyl ester(1)、oxohydrastinine(2)、pinoresinol(3)。结论 化合物1为新型苄基异喹啉生物碱。

Crystal Structure of Isoquinoline Derivatives

The chiral compound 5H-imidazol[2,3-b]isoquinoline-l-ethanol-5-one-1,2, 3, 10b-tetrahydro- β（S）-phenyl-3（S）-phenyl was synthesized from the direct condensation of 2- cyanophenyacetonitrile with optically active （S）-（＋）-2-phenylglycinol in chlorobenzene under dry, anaerobic conditions. ZnCl2 was used as a Lewis acid catalyst in this reaction, and the structure of this compound was determined by X-ray diffraction, NMR, MS and IR. Crystal data of the title compound： C25H22N2O2, Mr = 382.45, P 21 21 21, a = 5.341（5）, b = 16.735（5）, c = 22.129（5） A, γ = 90°, V = 1978（2）A^3, Z = 4, Dc = 1.284 g/cm^3, the final R = 0.0321 for 2269 observed reflections with I 〉 2 σ（I） and Rw = 0.0771 for all data.

Cloning and characterization of an oxiranedicarboxylate hydrolase from Labrys sp. WH-1

Objective:This study aimed to clone and characterize the oxiranedicarboxylate hydrolase(ORCH) from Labrys sp.WH-1.Methods:Purification by column chromatography,characterization of enzymatic properties,gene cloning by protein terminal sequencing and polymerase chain reaction(PCR),and sequence analysis by secondary structure prediction and multiple sequence alignment were performed.Results:The ORCH from Labrys sp.WH-1 was purified 26-fold with a yield of 12.7%.It is a monomer with an isoelectric point(pl) of 8.57 and molecular mass of 30.2 kDa.It was stable up to 55℃with temperature at which the activity of the enzyme decreased by 50% in 15 min(T5015) of 61℃and the half-life at 50℃(t1/2,50℃) of 51 min and was also stable from pH 4 to 10,with maximum activity at 55℃and pH 8.5.It is a metal-independent enzyme and strongly inhibited by Cu2+,Ag+,and anionic surfactants.Its kinetic parameters(Km,kcat,and kcat/Km) were 18.7 mmol/L,222.3 s-1,and 11.9 mmol/(L s),respectively.The ORCH gene,which contained an open reading frame(ORF) of 825 bp encoding 274 amino acid residues,was overexpressed in Escherichia coli and the enzyme activity was 33 times higher than that of the wild strain.Conclusions The catalytic efficiency and thermal stability of the ORCH from Labrys sp.WH-1 were the best among the reported ORCHs,and it provides an alternative catalyst for preparation of L(+)-2,3-dihydrobutanedioic acid.

HPLC法测定拉莫三嗪中的有关物质

目的:建立拉莫三嗪原料药有关物质的HPLC测定方法。方法:采用Feini Gen Red ClassicalⅡC18(250 mm×4.6 mm,5μm)色谱柱,对拉莫三嗪的有关物质进行定量分析,以磷酸二氢钾缓冲液(取磷酸二氢钾2.7 g,加水800 m L使溶解,加三乙胺6.7 m L,用磷酸调节p H至2.0,加水至1 000 m L)为流动相A,乙腈为流动相B,梯度洗脱,流速为1.5 m L·min-1,柱温为35℃,检测波长为210 nm(用于检测2,3-二氯苯甲酸)和270 nm(用于检测除2,3-二氯苯甲酸外的其他杂质)。用HPLC-MS鉴定氧化降解溶液中未知杂质;采用Thermo AcclaimTM120 C18(250 mm×4.6 mm,5μm)色谱柱,以甲醇-水(50∶50)为流动相,ESI离子源,正离子扫描方式,检测离子m/z为272。结果:主峰与各有关物质峰分离度良好,拉莫三嗪及各有关物质在质量浓度为0.3~4.0μg·m L-1范围内呈良好的线性关系(r2=0.998 7),拉莫三嗪的定量下限为0.2μg·m L-1(270 nm)、杂质Ⅰ的定量下限为0.2μg·m L-1(210 nm)。3批样品有关物质测定结果显示,已知杂质和未知杂质均未检出。结论:本法可为拉莫三嗪质量控制提供参考。