A Convenient Synthesis of cis and trans-(±)-4-Amino-1-[2-(hydroxyl-methyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone

A convenient synthesis of cis-(±) isomer 1 and trans-(±) isomer 2 of lamivudine starting from benzoyloxyacetaldehyde and l,4-dithiane-2,5-diol is described. The key steps include chlorination of oxathiolane lactol 5 by SOCl2/DMF, followed by coupling with silylated N4-acetylcytosine and deprotection. The overall yield was 42.6 % and 20.1 %, respectively.     

相变温度低且宽的含有胆甾烯基和反式-4-烷基环己基苯氧基的二介晶化合物

Unsymmetrical dimesogenic compounds with cholesteryl and 4-（trans-4-n-alkylcyclohexyl）phenoxy parts were synthesized by condensation of cholester-3-yl 6-bromohexanoate with appropriate 4-（trans-4-n-alkylcyclohexyl）- phenols. Structures and thermal phase behaviour of these dimesogenic compounds have been confirmed by IR, IH NMR, elemental analysis, DSC, polarity microscopy and XRD measurements. Their thermal phase behaviour was significantly different with that of other cholesterol-based dimesogens while they exhibited low and wide phase transition temperature.     

4-(4-羟基丁基－2－炔氧基)－3-（苯磺酰基）－1，2，5－噁二唑－2－氧化物与牛血清白蛋白结合作用的光谱法研究

The interaction between 4-(4-hydroxybut-2-ynyloxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide(FB)andbovine serum albumin(BSA)was studied by spectroscopic methods including fluorescence and UV-Vis absorptionspectroscopy.The quenching mechanism of fluorescence of BSA by FB was considered to be a dynamic quenchingprocedure.The number of binding sites n and apparent binding constant K were measured by fluorescence quench-ing method.The results indicate that there is FB molecular binding with BSA,and forming 1∶1 complex.Thethermodynamic parameters such as ΔH,ΔG and ΔS,etc.,were calculated.The results indicate that the binding reac-tion is mainly entropy-driven and hydrophobic forces play major role in the binding reaction.The distance r be-tween donor(BSA)and acceptor(FB)was obtained according to Frster theory of non-radioactive energy transfer.     

具有U构型的二{1-甲硫基-1-[1-苯基-1-(1-苯基-3-甲基-5-氧代-4,5二氢吡唑-4-烯)-甲氨基]亚氨甲基}二硫醚的晶体结构

The reaction of 1-phenyl-3-methyl-4-benzoyl-2,5-dihydro-1H-pyrazol-5-one (PMBP) and methyldithiocarbazate (mdtc) in methanol results in formation of a yellow crystalline solid, adduct of 1-phenyl-3-methyl-4benzoyl-2,5-dihydro-lH-pyrazol-5-one and methyldithiocarbazate. When the yellow solids were dissolved in a mixture of methanol and ether (1:4), a red crystal, which is an oxidation product of the former, was obtained by allowing solvent to evaporate for a few days at room temperature. The X-ray analysis of the red crystal indicates that it is a novel disulfide with a special structure like a “U” conformation in the solid state.     

The Application of Suzuki Coupling Reaction on the Preparation of Carbosilane Dendrimers with 4-（Naphthalen-l-yl）phenyl Core

Carbosilane dendrimers with p-bromophenyl core were synthesized by alternating Grignard and hydrosilylation reaction. And the α-naphthalenyl was connected to the core by the Suzuki coupling reaction. A new carbosilane dendrimer with big π-conjugated structure [4-（naphthalen-l-yl）phenyl core] was given. It shows Suzuki coupling reaction is an effective and powerful core-functionalization method and the satisfactory result can be obtained through prolonging the reaction time with the increase of the generation of dendrimer.     

银盐法合成6-(4-卤代苯基)-3(2H)-哒嗪酮葡萄糖苷

Four pyridazinone gluosodes 4 were synthesized by Koenig' s-Knorr reaction of 6-(4-halophenyl)-3 (2H)-pyridazinone silver salt 2 with bromoaeetylglueose 3. Treatment of 4 with dry ammonia at 0 ～ - 5 ℃ effeeted a removal of the acetyl protecting groups to yield compounds 5. When the substituent on the benaene ring was F-or Cl-,O-glueoside was synthesized prineipaUy. However, when the substituent was Br-or I-, N-glueoside was mainly obtained. Their struetures were confirmed by ^1H NMR, IR and elemental analysis.     

POLYMERIZATION MECHANISM OF DIENES WITH HOMOGENEOUS RARE EARTH CATALYSTS

The reaction mechanisms of diene polymerization with homogeneous rare earth catalyst are studied by means of the spectra of ~1H-NMR, one-and two-dimensions ~(13)C-NMR. Based on the data of above NMR spectra, it is proposed that the polymerization reaction proceeds according to the following mechanism: η~4-diene (cis-(?)trans-)and η~3-allyl (syn-(?)anti-).     

Synthesis and Crystal Structure of {4-[2-（9- Hexyl-9H-carbazol-3-yl）vinyl]phenyl} Dimethylamine

The title compound {4-[2-(9-hexyl-9H-carbazol-3-yl)vinyl]phenyl} dimethylamine has been synthesized by the well known Wittig reaction, and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P21/c with a = 47.87(2), b = 10.222(4), c = 9.612(4) , β = 92.401(9)o, V = 4699(3) 3, Z = 8, C28H32N2, Mr = 396.56, Dc = 1.121 g/cm3, F(000) = 1712 and μ(MoKa) = 0.065 mm-1. The final R and wR are 0.0793 and 0.1983, respectively for 3524 observed reflections with I > 2σ(I). In the title compound, the bond lengths are normal, and the crystal is stabilized by Van der Waals’ forces.     

Synthesis and mesomorphic properties of 4-(4-bromopropyloxy)-4’-(4-alkyloxybenzylidene)anilines

This article describes the preparation and liquid crystalline properties of a new homologous series of 4-（4-bromopropyloxy）-4’- （4-alkyloxybenzylidene）anilines in which the phenyl ring is armed by a bromopropyloxy chain.The thermal behavior and mesomorphic properties of the synthesized compounds were studied with particular attention given to the correlation between their phase transition temperatures and anisotropic change influenced by molecular structure.All the members displayed enantiotropic smectic phase except for the homologue with the longest alkyloxy chain(R = C₁₈H₃₇),exhibiting only monotropic characteristic. The presence of bromine atom from the propyloxy side chain is found to be capable of altering and influencing the mesomorphic properties.     

Syntheses and Bioactivities of 4-Ar-2-oxo-glutaric Acids

Fourteen novel compounds were synthesized and characterized by using NMR and ESI-MS methods. The bioactivities of the four novel 4-Ar-2-oxo-glutaric acids were studied by using the LC-MS method. The experimental results show that 3-nitrobenzyl-2-oxo-glutaric acid is a mild inhibitor for the hydroxylation reaction catalyzed by PHD2. The decarboxylated peak for 3-fluorobenzyl-2-oxo-glutaric acid was observed by using the negative LC-MS method, indicating that it can be used as a mild cosubstrate to replace 2-OG, but this is possible only in the presence of the prime peptide CODD 19 mer.     

A concise synthesis of a very late antigen-4 antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid via reductive etherification

This contribution describes a concise synthesis to ethyl trans-[(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate (2b) as a key intermediate of very late antigen-4 (VLA-4) antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (1). The synthesis employs a reductive etherification as a key reaction using (2S,4S)-1-benzyloxycarbonyl-4-methoxypyrrolidine-2-carboxyaldehyde (12) and trans-4-triethylsilyloxycyclohexanecarboxilic acid ethyl ester (13b). This synthesis provides 2b in 6 steps with 38% overall yield from commercially available starting material.     

Synthesis of new trans-2-benzyl-3-(furan-2-yl)-4-substituted-1,2,3,4-tetrahydroisoquinolinones

The reaction of homophthalic anhydride and N-(furan-2-yl-methylidene)- benzylamine in different solvents and varying temperatures was studied in detail. Mixtures of the expected trans- and cis-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acids trans-5 and cis-5, along with by-products 6 and 7 were obtained in dichloroethane or benzene. In pyridine, used for the first time, the reaction became completely diastereoselective, giving only the trans isomer. The carboxylic acid group of trans-5 was transformed in four steps into cyclic aminomethyl groups which yielded various new tetrahydroisoquinolinones trans- 11a-g, incorporating both a known fragment of pharmacological interest and various pharmacophoric substituents.     

Synthesis of trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines via ring-closing metathesis reaction

[reaction: see text] trans-(3S)-Amino piperidines bearing various alkyl and aryl substituents at the C-4 position were synthesized via a ring-closing metathesis reaction. The absolute stereochemistry was controlled using a protected D-serine as a starting material. Stereoselective hydrogenation of allylamines provided trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines. This procedure presents the first method for the asymmetric synthesis of 4-substituted 3-amino piperidines.     

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.     

苯乙烯基氮氧杂芳烃间的交叉光二聚反应

用中压汞灯(λ > 300 nm)照射4-苯乙烯基吡啶、2-苯乙烯基苯并噁唑和5-苯基-2-苯乙烯基噁唑三种杂芳基乙烯单体中任意两种的硫酸水溶液，得到三种交叉二聚体.用高效液相色谱跟踪研究了交叉光二聚反应，发现每组反应生成三种光二聚体，其中二种为单体自身的光二聚体，而另外一种是两种不同单体的交叉光二聚体.交叉二聚体通过柱色谱分离得到，其顺式头对尾结构经紫外、红外、氢谱、碳谱和元素分析确定.用紫外光谱和高效液相色谱跟踪研究了交叉光二聚体的稀溶液在低压汞灯（λmax=254 nm）照射下的光解反应.研究发现交叉二聚体能够彻底发生光解，首先生成原来的反式单体，所生成的反式单体容易发生异构化而生成顺式单体，最终建立起反顺异构化平衡.     

聚苯乙烯基吡啶甲基氧乙烯醚的光化学性质

通过亲核取代反应将苯乙烯基吡啶功能基引入到聚氯甲基氧乙烯醚侧链上,制备出具有聚氧乙烯醚骨架的含有苯乙烯基吡啶盐功能基的线形光功能聚合物,该聚合物具有良好的水溶性.系统研究了上述光功能聚合物以及小分子参比物一氯化-N-丁基苯乙烯基吡啶盐的水溶液在不同紫外光照射下的光化学性质,发现参比物在长波紫外光(波长以365 nm为主)照射下只发生反-顺异构化,而所合成的光功能聚合物在同样紫外光照射下不仅能够发生反-顺异构化,而且能够发生功能基之间的光环加成反应.研究还发现,已经过照射发生光环加成反应的产物,在短波紫外光(波长为254 nm)照射下还可以发生快速光解开环反应.     

衍生化法合成高纯度顺式对叔丁基环己醇

由对叔丁基苯酚催化加氢合成顺/反对叔丁基环己醇的混合物。用适量的叔丁基二甲基氯硅烷(TB-DMSCl)衍生化反应,得顺式对叔丁基环己醇的纯度可达99.5%以上。加氢反应条件实验表明,当浓盐酸加量为0.25 g、异丙醇为溶剂和温度70～80℃时反应效果最佳。根据衍生化数据对顺/反对叔丁基环己醇分离的反应机理进行了推测。     

Stereocontrolled synthesis of (-)-kainic acid from trans-4-hydroxy-L-proline

[reaction: see text] A highly stereoselective synthesis of (-)-kainic acid has been achieved in 14 steps and >7% overall yield starting from inexpensive trans-4-hydroxy-L-proline. The key steps are diastereoselective enolate alkylation and cuprate substitution reactions.     

Study of the reaction of cis- and trans-4-acylamino-3-hydroxythiophans with thionyl chloride

The reaction of cis- and trans-4-acylamino-3-hydroxythiophans with thionyl chloride was studied. It was found that chlorosulfites are initially formed with retention of the configuration of the starting compound. 2-Substituted 3a,4,6,6a-tetrahydrothieno[3,4-d]oxazoline is formed from trans-4-acylamino-3-chlorosulfitothiophans by thermal reaction or in the presence of pyridine, whereas trans-4-acylamino-3-chlorothiophans are obtained from cis-4-acylamino-3-chlorosulfitothiophans; both reactions proceed with inversion of configuration.     

Prototropic isomerization of trans-4-benzamido-3-hydroxy-2-(4-carbomethoxybutylidene)thiophan to cis- and trans-4-benza mido-3-oxo-2-(4-carbomethoxybutyl) thiophan

trans-4-Benzamido-3-hydroxy-2-(4-carbomethoxybutylidene)thiophan (I) was prototropically isomerized in the presence of hydrogen chloride. It is shown that the two possible isomers cis- and trans-4-benzamido-3-oxo-2-(4-carbomethoxybutyl)thiophan — are formed in the process.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 2, pp. 175–177, February, 1973.