Synthesis and Crystal Structure of （R）-4-Hydroxymethyl-2-thioxo Thiazolidine and Its Asymmetric Catalysis

(R)-4-Hydroxymethyl-2-thioxo thiazolidine as a new chiral catalyst in the asymmetric addition of diethyl-zinc to benzaldehyde was synthesized from (R)-4-hydroxymethyl-2-thioxo thiazolidine carboxylic acid and its crystal structure was determined by X-ray diffraction method. The compound was crystallized in the orthorhombic system, space group P212121 with unit cell dimensions a=0.67253(12) nm; b=0.89164(17) rim; c=1.06146(19) nm, volume 0.6365(2) nm3; Z=4, calculated denisity 1.557 Mg/m3; absorption coefficient 0.733 mm-1; F(000)=312. The X-ray crystal structure analysis reveals that the compound has a thione group.     

手性2-(2-吡啶基)-4-羧乙基-1,3-噻唑烷的合成及应用研究

以分级结晶和柱层析法对手性配体2-(2-吡啶基)-4-羧乙基-1,3-噻唑烷(A)进行了异构体分离提纯。将其与[Rh(COD)Cl]_2制备的原位催化剂用于催化苯乙酮及其它几种芳香酮的不对称硅氢化反应,化学收率达90％左右,光学纯度达80％e.e.左右,噻唑烷环上的C_2构型对催化反应结果无影响,C_4位上酯基的影响也不大。     

Exploring structural feature of aldose-reductase inhibition by 5-[[2-(omega-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives employing Fujita-Ban and Hansch approach

Designing of a highly selective, potent and safe inhibitor of aldose reductase (ALR) capable of potentially blocking the excess glucose flux through the polyol pathway that prevails under diabetic condition has been a long standing challenge. In our study, we did quantitative structure-activity relationship (QSAR) analysis, based on Fujita-Ban and classical Hansch approach, on 5-[[2-(omega-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives. Study gave structural insight into the binding mode of the molecules to the aldose reductase enzyme. The Fujita-Ban approach revealed that benzylidene thiazolidine nucleus is more potent as compare to naphthyl-methylene thiazolidine analogs. The bulkierness of naphthyl-methylene might be inquisitive with receptor. Hansch approach suggested that electron-withdrawing groups are conducive to aldose reductase inhibitory activity.     

Acylation of the 4,5- and 5,6-double bond isomers of 3-steroidal thiazolidines: The chemical stability of spiro-3-steroidal 4,5- and 5,6-double bond isomers

It has been shown that the 5,6-double bond steroidal thiazolidines can be N-acylated if there is no substituent in the 4'-position on the thiazolidine ring; substituents in the 4'-position of the thiazolidine sterically hinder acylation. On the other hand, the 4,5-double bond steroidal thiazolidine isomers decomposed on attempted acylation. The lability of these 4,5-double bond isomers was attributed to the contribution of a hyperconjugative resonance form to the structure of the 4,5-double bond isomers.     

Nucleophilic Substitutions of N-Acyl-4-Chloro-3-Thiazolidines with the Organometallic Selenolates LiSeMcp(CO)3, M = Mo,W. Crystal Structure of (RS)-3-Acetyl-4-[(η5-cyclopentadienyl)(tricarbonyl)selenolato-tungsten(II)]-2,2,5,5-tetramethyl-3-thiazolidine

Selenolato complexes of molybdenum(II) and tungsten(II) with biologically important thiazolidine N/S-heterocycles have been prepared via nucleophilic attack of LiSeMocp(CO)₃ or LiSeWcp(CO)₃ on N-acyl-4-chloro-thiazolidines, easily accessible by reaction of acyl chlorides with 3-thiazolines. The resulting complexes represent the first examples of organometallic derivatives of this class of heterocycles. They are stable under nitrogen in the solid state, but decompose in solution when exposed to air. An X-ray structure analysis of (RS)-3-acetyl-4-[(η⁵-cyclopentadienyl)(tricarbonyl)(selenolato)tungsten(II)]-2,2,5,5-tetramethyl-3-thiazolidine ( 2 a ) has been performed (C₁₇H₂₁NO₄SSeW, orthorhombic, Pbca, a = 1579.5(3) pm, b = 1138.7(2) pm, c = 2209.4(3) pm, Z = 8). It revealed a monomeric structure with a non-planar heterocyclic substituent in an envelope conformation and a W–Se bond length of 264.96(10) pm. ⁷⁷Se-NMR spectra displayed chemical shifts in the range –280 to –350 ppm. These values are consistent with earlier results on related complexes.     

Investigation of 3-(carbazol-9-YL)-1,2-epithiopropane interaction with aromatic amines

In the reaction of 9-(2,3-epithiopropyl)-9H-carbazole with aromatic amines (aniline, 4-methoxy-, 4-methyl-, 4-fluoro-, 4-bromo-, 4-chloro-, 3-chloro-, 2-chloroaniline) and subsequent oxidation of the mixtures formed of propanethiols and disulfides with 25% H₂O₂ in basic solutions the respective disulfides have been synthesized. Carbazolyl-containing derivatives of the thiazolidine have been obtained.Published in Khimiya Geterotsiklicheskikh Soedinenii. No. 1, pp. 90–99, January, 2000.     

光学活性N-肉桂酰R(S)-4-异丙基四氢噻唑-2-硫酮的合成及其量子化学的研究

用KBH_4,CaCl_2为还原剂使D及L缬氨酸甲酯还原得到光学活性产物R-3-甲基-2-氨基丁醇(2a)及S-3-甲基-2-氨基丁醇(2b)。2a,2b同CS_2在KOH存在下反应得到(R)-4-异丙基四氢噻唑-2-硫酮(3a)及(S)-4-异丙基四氢噻唑-2-硫酮(3b)。肉桂酰氯分别同3a及3b在Et_3N存在下反应得到N-肉桂酰(R)-4-异丙基四氢噻唑-2-硫酮(4a)及N-肉桂酰(S)-4-异丙基四氢噻唑-2-硫酮(4b)。用半经验的量子化学PM3方法研究了反应物和产物的电子结构,得到了产物的最优构型和电荷键序分布以及反应焓变。     

Improvement of solubility and oral bioavailability of 2-(N-cyanoimino)-5-[(E)-4-styrylbenzylidene]-4-oxothiazolidine (FPFS-410) with antidiabetic and lipid-lowering activities in dogs by 2-hydroxypropyl-beta-cyclodextrin

2-(N-Cyanoimino)-5-[(E)-4-styrylbenzylidene]-4-oxothiazolidine (FPFS-410) is a newly synthesized thiazolidine derivative having not only antidiabetic but also lipid-lowering activities. However, this compound has an extremely low aqueous solubility (2.8 (+/-0.33) x 10(-8) M (0.0094+/-0.0011 microg/ml) in 1.0 M phosphate buffer (pH 7.0) at 25 degrees C). In this study, we investigated the effect of various hydrophilic cyclodextrins (CyDs) on the solubility of FPFS-410 to select a CyD suitable for formulations of the compound. Among various CyDs, 2-hydroxypropyl-beta-CyD (HP-beta-CyD) had the highest solubilizing ability to FPFS-410, e.g., the solubility of the compound was increased 200000-fold by the addition of 40 mM HP-beta-CyD, which was attributable to the formation of the 1 : 2 (guest : host) inclusion complexes. The interaction of HP-beta-CyD with FPFS-410 was studied using 1H-nuclear magnetic resonance (NMR) spectroscopies including ROESY spectroscopy and a molecular modeling calculation. These results suggested that HP-beta-CyD forms a 1:2 (guest : host) inclusion complex with FPFS-410 by including both the stilbene and thiazolidine moieties. FPFS-410/HP-beta-CyD solid complexes with various stoichiometries were prepared by the spray drying and cogrinding methods, and confirmed by powder X-ray diffractometry that these complexes are in an amorphous state. The dissolution of FPFS-410 in water was significantly accelerated by the complexation with HP-beta-CyD. In vivo studies revealed that HP-beta-CyD markedly increases the bioavailability of FPFS-410 after oral administration in dogs. The present results suggest that HP-beta-CyD is useful for improvement of the extremely low bioavailability of FPFS-410.     

Structure and Biological Activities of 3-Phenyl-2-[1-benzoyl-1- （1,2,4-triazol-1-yl）] Methenyl Thiazolidine

The title compound 3-phenyl-2-[1-benzoyl-1-(1,2,4-triazol-1-yl)]methenyl thiazolidine was synthesizedfrom acetophenone, triazole, phenylthioisocyanate and 1,2-dibromo-ethane by several step reactions. Itsstructure was identified by means of ^1H NMR, MS and IR spectrometries. The single crystal structure of 3-phenyl-2-[1-benzoyl-1-(1,2,4-triazol-1-yl)]methenyl thiazolidine was determined by X-ray diffraction.The preliminary bioassays have shown that the title compound exhibits the weak activities of fungicide andplant growth regulator.     

Smectic A and smectic C materials: partially deuteriated chiral liquid crystals (S)-(-)-2-methylbuty 4-(4-(d13)-hexyloxyphenyl)benzoate and (S)-(-)-2-methylbutyl 4-(4-(d17)-octyloxyphenyl)benzoate

In order to study the difference in microscopic orientation of ferro- and antiferroelectric liquid crystalline molecules, we synthesized the partially deuteriated chiral compounds, (S)-(^-)-2-methylbutyl 4-(4-(d₁₃)-hexyloxy- and (S)-(^-)-2-methylbutyl 4-(4-(d₁₇)-octyloxy-phenyl)benzoates. Fundamental physical properties such as phase transition temperatures, spontaneous polarization and tilt angle were determined. Polarized FTIR measurements were also made to provide information on molecular structure and orientation.     

Structure determination of bis{(4Z)-1-(2-azidoethyl)-4-[(pyridin-2-yl)methylidene]-2-thiolatoimidazol-5(4H)-one}dicopper chloride from X-ray powder diffraction data

The new tridentate organic N₂S-type ligand, (4Z)-1-(2-azidoethyl)-4-[(pyridin-2-yl)-methylidene]-2-thioxoimidazol-5(4H)-one (LH), was synthesized. The reaction of LH with copper(II) chloride in a CH₂Cl₂/MeOH mixture afforded the coordination compound of the composition L₂Cu₂Cl (3). The crystal structure of 3 was solved and refined from X-ray powder diffraction data. Complex 3 has a binuclear structure with a short interatomic Cu-Cu distance and one bridging chlorine atom, which is located almost symmetrically with respect to both metal atoms. The planar organic ligands are noncoplanar and are at an angle of 53.56(1)° to each other.     

Some reactions of 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido) acetic acids

In situ generated 2,4-diaryl substituted münchnones from 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids react with acetic anhydride in the presence of 2-nitromethylene thiazolidine, which is most likely acting as a base, and unexpectedly undergo a Dakin–West type reaction and a concurrent autoxidation reaction leading to the formation of (E)-1-(N,4-dimethylbenzamido)-1-(4-fluorophenyl)prop-1-en-2-yl acetate, 4-substitutedphenyl-N-methyl-N-(4-substitutedbenzoyl) benzamides and p-substituted benzoic acids. In addition, a novel and efficient access to N-acyl urea derivatives is described by the reaction between 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids and cyclohexyl, isopropyl carbodiimides in the presence of a base. The structures of all new products were identified on the basis of NMR and IR spectra, along with X-ray diffraction data and HRMS measurements.     

An unusual labilization of a 4-(trifluoromethyl)thiazole

N-Chloro-4-(trifluoromethyl)-5-thiazolyl-N',N'-diethylurea 5 has been found to undergo a facile labilization of the trifluoromethyl group under mild conditions. The reaction relies on the assistance of the nitrogen substitution at the 4-position of the thiazole ring. Treatment of 5 with triethylamine and either methanol or methanethiol replaced the trifluoromethyl group with a methyl ester or a trimethylorthothio ester respectively at room temperature. Combination of 5 with diethylamine led to an unusual thiazolidine with two exocyclic double bonds, 8 .     

3-(9-芴甲氧羰基)四氢噻唑-2-硫酮的合成及其晶体结构

在吡啶存在下, 由9-芴甲氧羰酰氯与四氢噻唑-2-硫酮反应得到3-(9-芴甲氧羰基)四氢噻唑-2-硫酮, 产率为78.0%。用X射线衍射法测定晶体结构, 属正交晶系, Pca21空间群, 晶体学参数:a=0.9654(2), b=2.8032(1), c=0.6069(2)nm, Z=4。分子中的C=O与C=S基团处在C(3)-N-C(4)键的同侧, 为顺式结构。用PM3分子轨道方法研究该化合物的电子结构、电荷和键序分布、前线轨道性质。     

Reaction of 2-imino-3-aryl-4-oxothiazolidines with phenyl isothiocyanate

2-Phenylthiocarbamoylimino-3-aryl-4-oxothiazolidines, which are hydrolyzed at the C=N and N₃=C₄ bonds of the thiazolidine ring to give 3-arylthiazolidine-2,4-diones, N-phenylthiocarbamoylarylpseudothiohydantoic acids, and 3-phenylthiocarbamoylthiazolidine-2,4-dione, were synthesized by reaction of 2-imino-3-aryl-4-oxothiazolidines with phenyl isothiocyanate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 903–905, July. 1976.     

Synthesis and stereochemical studies of 2‐substituted thiazolidine‐4‐carboxamide derivatives

A series of new 2‐substituted thiazolidine‐4‐carboxamide derivatives which have potentially useful immunological properties, have been synthesized in a stereoselective manner by coupling 2‐subsituted thiazolidine‐4‐carboxylic acids with amines or amino esters. The structure of these compounds was established by combination of NMR methods and by X‐ray analysis.     

1-[4-(二甲氨基)苯亚甲基氨基]-4-苯基硫脲的另一个手性对映体晶体结构

对-二甲氨基苯甲醛和苯基氨基硫脲缩合反应生成1-[4-(二甲氨基)苯亚甲基氨基]-4-苯基硫脲(DMB), 产物能从溶液中析出单一手性对映体晶体. 用单晶X射线衍射技术测定了它的绝对构型, 晶体属正交晶系, P2₁2₁2₁空间群, a＝0.7870(2) nm, b＝1.1560(2) nm, c＝1.6668(3) nm, V＝1.5164(5) nm³, Z＝4, D_c＝1.307 g/cm³, F(000)＝632, μ＝0.213 mm^－1, 2557个可观测点[I＞2s(I)]精修的最终残差因子: R＝0.0409, wR＝0.1061, Flack参数为0.00(9), 能够确定绝对构型. 化合物的晶体结构和大宗粉末样品的固体圆二色谱表明化合物在结晶过程中发生单一对映体的手性堆积.     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.