Arenesulfonylimines of methyl trifluoropyruvate in the cyclocondensation reactions with 1,3-C,N-and-N,N-binucleophiles

Reaction of arenesulfonylimines of methyl trifluoropyruvate with 1,3-C,N-and-N,N-binucleophiles led to a variety of N-sulfonylated fluorine-containing heterocycles, including the fused ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2171–2175, November, 2007.     

Complexes of cobalt(2+) chloride with hydrochlorides of N-(1,2,4-triazol-5-yl)- and N-(tetrazol-5-yl)benzamidines

We have synthesized complex compounds of Co(2+) chloride with hydrochlorides of N-(1,2,4-triazol-5-yl)benzamidine and N-(tetrazol-5-yl)benzamidine. According to magnetochemistry and electron spectroscopy data, the ligands are coordinated in a bidentate fashion with the N atom of the amidine group and the N atom of the heterocycle with formation of the tetrahedral chromophore CoN₂Cl₂.Institute of Inorganic Chemistry, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2311–2315, October, 1992.     

Direct synthesis of 3,5-diaryl-1,2,4-oxadiazoles using 1-(2-oxo-2-arylethyl)pyridin-1-iums with benzamidines

An efficient domino protocol for the synthesis of 1,2,4-oxadiazole derivatives from readily available 1-(2-oxo-2-arylethyl)pyridin-1-iums and amidine hydrochlorides was developed. In this practical approach, N-acyl amidine precursors were formed firstly via a simple nucleophilic substitution, without the purification of N-acylamidine intermediates, and the following intramolecularly dehydrative cyclization gave 1,2,4-oxadiazole derivatives in the presence of I₂/K₂CO₃/DMSO, which exhibited excellent functional group tolerance and proceeded under simple experimental conditions.     

Solid phase synthesis of benzamidine and butylamine-derived hydantoin libraries

We have constructed a number of benzamidine- and butylamine-based hydantoin compounds by means of an efficient route using solid phase synthesis in which neat diisopropylamine was employed for a novel cyclization/traceless cleavage step. All library compounds were obtained in excellent yield and high purity. This revised version was published online in August 2006 with corrections to the Cover Date.     

Development of an enzyme-linked immunosorbent assay (ELISA)-like fluorescence assay to investigate the interactions of glycosaminoglycans to cells

Sulfated glycosaminoglycans were labeled with biotin to study their interaction with cells in culture. Thus, heparin, heparan sulfate, chondroitin 4-sulfate, chondroitin 6-sulfate and dermatan sulfate were labeled using biotin-hydrazide, under different conditions. The structural characteristics of the biotinylated products were determined by chemical (molar ratios of hexosamine, uronic acid, sulfate and biotin) and enzymatic methods (susceptibility to degradation by chondroitinases and heparitinases). The binding of biotinylated glycosaminoglycans was investigated both in endothelial and smooth muscle cells in culture, using a novel time resolved fluorometric method based on interaction of europium-labeled streptavidin with the biotin covalently linked to the compounds. The interactions of glycosaminoglycans were saturable and number of binding sites could be obtained for each individual compound. The apparent dissociation constant varied among the different glycosaminoglycans and between the two cell lines. The interactions of the biotinylated glycosaminoglycans with the cells were also evaluated using confocal microscopy. We propose a convenient and reliable method for the preparation of biotinylated glycosaminoglycans, as well as a sensitive non-competitive fluorescence-based assay for studies of the interactions and binding of these compounds to cells in culture.     

抑制剂Benzamidine与胰岛素作用机制的分子动力学和结合自由能计算研究

氢键和极性相互作用在抑制剂-蛋白结合专一性识别过程中起到重要作用.抑制剂Benzamidine(BEN)与胰岛素trypsin相互作用机制的阐明有助于胰岛素高效抑制剂的研发.本文采用分子动力学模拟和MM-PBSA(molecular mechanics-Poisson Boltzmann surface area)从原子层次上研究BEN与胰岛素的结合模式.结果表明抑制剂BEN的脒基不仅与Asp189的羰基产生静电相互作用,而且与残基Ser190和Gly214形成氢键相互作用.基于残基能量分解的计算表明抑制剂的苯基与残基His58,Cys191,Gln192,Trp211,Gly212和Cys215形成有利于抑制剂结合的疏水性相互作用.期望当前的研究能为胰岛素有效抑制剂的研发提供重要的理论指导.     

A Transition‐Metal‐Free Synthesis of Multisubstituted Imidazoles

A novel and simple t‐BuOLi/I₂‐mediated synthesis of 1,2,4‐trisubstituted imidazoles was developed without transition‐metal added. The transition‐metal‐free strategy tolerated a range of substrates and provided products in moderate to good yields with 100% regioselectivity.     

Palladacycles bearing pendant benzamidinate ligands as catalysts for the Suzuki and Heck coupling reactions

Three pendant benzamidines [Ph-C(NC₆H₅)-{NH(CH₂)₂NMe₂}] (1), [Ph-C(NC₆H₅)-{NH(CH₂Py)}] (2) and [Ph-C(NC₆H₅)-{NH(o-C₆H₄)(oxazoline)}] (3) are described. Reactions of 1, 2 or 3 with one molar equivalent of Pd(OAc)₂ in THF give the palladacyclic complexes [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂)₂NMe₂}]Pd(OAc) (4), [Ph-C{-NH(η¹-C₆H₄)}{N (CH₂Py)}]Pd(OAc) (5) and [Ph-C{-NH(η¹-C₆H₄)}{N(o-C₆H₄)(oxazoline)}]Pd(OAc) (6), respectively. Treatment of 4, 5 or 6 with excess of LiCl in chloroform affords [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂)₂NMe₂}]PdCl (7), [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂Py)}]PdCl (8) and [Ph-C{-NH(η¹-C₆H₄)}{N(o-C₆H₄)(oxazoline)}]PdCl (9). The crystal and molecular structures are reported for compounds 1, 3, 5, 6 and 7. The application of these palladacyclic complexes to the Suzuki and Heck coupling reactions was examined.     

Some features of the crystal and molecular structure of N-(1,2,4-triazol-5-yl)benzamidine and its hydrochloride

The crystal and molecular structures of N-(1,2,4-triazol-5-yl)benzamidine (1) and its hydrochloride (2) were determined by x-ray crystallography. In compound 1 both independent molecules are Z isomers of the anidine substituted in the imino group and 5-substituted 1H-1,2,4-triazoles. In the crystal the molecules of compound 1 are linked into a stable dimer by intermolecular hydrogen bonds. An undissociated HCl molecule was unexpectedly found in the structure of compound 2, while the structure of the base corresponded to the Z isomer of the amidine substituted in the amino group and to 2H-1,2,4-triazole substituted at position 5. The structures of compounds 1 and 2 are stabilized by an intramolecular hydrogen bond. The HCl molecule participates in the formation of intermolecular hydrogen bonds in compound 2.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 6, pp. 1380–1386, June, 1992.