O6-(benzotriazol-1-yl)inosine derivatives: easily synthesized, reactive nucleosides

A novel class of O6-(benzotriazol-1-yl)inosine as well as the corresponding 2'-deoxy derivatives can be conveniently prepared by a reaction between sugar-protected or -unprotected inosine or 2'-deoxyinosine nucleosides and 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). The reaction appears to proceed via a nucleoside phosphonium salt, and in the absence of any additional nucleophile, the released 1-hydroxybenzotriazole undergoes reaction with the formed phosphonium salt leading to the requisite O6-(benzotriazol-1-yl)inosine or 2'-deoxyinosine derivatives. Isolation and characterization of the phosphonium salt as well as analysis by 31P{1H} NMR appear to be consistent with this reaction pathway. The resulting O6-(benzotriazol-1-yl)inosine derivatives are effective as electrophilic nucleosides, undergoing facile reactions with a variety of nucleophiles such as alcohols, phenols, amines, and a thiol. Unusual and challenging nucleoside derivatives such as an aryl-bridged dimer, a nucleoside-amino acid conjugate, and a nucleoside-nucleoside dimer have also been synthesized from the O6-(benzotriazol-1-yl)-2'-deoxyinosine derivative. Finally, a fully protected DNA building block, the O6-(benzotriazol-1-yl)-2'-deoxyinosine 5'-O-DMT 3'-O-phosphoramidite, has been prepared and a preliminary evaluation of its use for DNA modification has been performed. Results from these studies indicate several important facts: A single, simple methodological approach provides a class of stable, isolable ribo and 2'-deoxyribonucleoside derivatives that possess excellent reactivity for SNAr chemistry with a wide range of nucleophiles. Also, a benzotriazolyl nucleoside phosphoramidite appears to be a suitable reagent for incorporation into DNA for purposes of site-specific DNA modification.     

New 4-(benzotriazol-1-yl)-1,2,3-triazole derivatives

A new 4-(benzotriazol-1-yl)-1,2,3-triazole structure was obtained by the diazotization reaction of either of 1-(2-aminophenyl)-4-carboxamido-5-amino-1H-1,2,3-triazole ( 1c ) or of the corresponding Dimroth isomer 1d . It underwent some common reactions to evaluate its chemical behaviour and structure. An analogous reaction sequence was carried out from the 2-nitro-4-methylphenyl azide, to assign the structure to the nitro derivatives prepared. The structure of the new compounds prepared was confirmed by chemical and spectroscopic methods.     

Preparation of various enantiomerically pure (benzotriazol-1-yl)- and (benzotriazol-2-yl)-alkan-2-ols

(S)-(−)-(Benzotriazol-1-yl)- and (S)-(−)-(benzotriazol-2-yl)-alkan-2-ols 7a–9a, 7b–9b and their (R)-(+)-acetates 10a–12a and 10b–12b were prepared in high enantiomeric excess via lipase from Pseudomonas fluorescens (Amano AK) catalyzed enantioselective acetylation of racemic alcohols 4a–6a and 4b–6b with vinyl acetate in tert-butyl methyl ether or toluene at 23 °C. The enantioselectivity of this transformation was dependent on the length of the alkyl chain with E-values ranging from 30 to 57. Several benzotriazole substituted ketones 1a–3a and 1b–3b were synthesized from 1H-benzotriazole and corresponding haloketones. These compounds were stereoselectively reduced with Baker’s yeast in water or in organic solvent containing 5% v/v of water at 30 °C to give the (S)-(−)-alcohol. Better stereoselectivity was observed in the kinetic resolution of racemic alcohols 4a–6a and 4b–6b (ee = 69–92% at 44–52% conversion) compared to reduction of corresponding prochiral ketones 1a–3a and 1b–3b with Baker’s yeast (ee = 40–67% at 39–89% conversion). Enhanced enantioselectivities were observed at lower temperatures.     

Synthesis of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides and their transformations to novel benzotriazol-1-yl-substituted cyclopropanes

Diphenylphosphinous anion reacted with chloromethylbenzotriazole to give (benzotriazol-1-yl)methyldiphenylphosphine oxide, which, after lithiation, was alkylated to give 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides in good yield. Treatment of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides with n-butyllithium followed by condensation with epoxides, afforded benzotriazol-1-yl-substituted cyclopropanes, which underwent further lithiation and subsequent reaction with numerous electrophiles to provide a variety of novel benzotriazol-1-yl-substituted cyclopropane derivatives.     

Generation and reactivity of polyanions derived from 1-[1-(benzotriazol-1-yl)alkyl]-1H-benzotriazoles

1-[1-(Benzotriazol-1-yl)alkyl]-1H-benzotriazoles undergo deprotonation with n-BuLi at the α-position of the N-substituent and at the 7-position of benzotriazole to afford polyanions. Treatment of these polyanions with electrophiles allows the preparation of highly functionalized benzotriazole derivatives.     

Reaction of 2,3-Bis(benzotriazol-1-yl)-1,4-naphthoquinone

Russian Journal of General Chemistry -     

An efficient general synthesis of 1-(benzotriazol-1-yl)alkyl esters

1-(Benzotriazol-1-yl)alkyl esters 2a-u were obtained in yields averaging 86% by the direct reaction of various aldehydes with the corresponding N-acylbenzotriazoles in the presence of a catalytic amount of potassium carbonate (10–25 mole %). The procedure was optimized by evaluating the effects of solvent, catalyst, temperature and other parameters.     

Synthesis and Transformations of 2-Hydroxy-2-(benzotriazol-1-yl)-1,4-naphthoquinone

2-Hydroxy-3-(benzotriazol-1-yl)-1,4-naphthoquinone reacts with o-phenylenediamine and 4-chloro-2-aminophenol to give cyclization products: 5-oxo-6-(benzotriazol-1-yl)-5,6H-benzo[a]phenazine and 5-oxo-6-(benzotriazol-1-yl)-10-chlorobenzo[a]phenoxazine; the reaction with aniline yields the quaternary anilinium salt, and benzoyl chloride and benzenesulfonyl chloride acylate the nitrogen atom of the benzotriazolyl moiety.     

Photochemical study of tris(benzotriazol-1-yl)methane

Photodecomposition of tris(benzotrizol-1-yl)methane (1) in benzene gives [1-benzotryazol-1-yl-methylidene]-biphenyl-2-ylamine (2) resulting from the loss of the benzotriazolyl radical and nitrogen followed by addition of benzene. Elimination of the second benzotriazolyl radical from 2 provides the biphenyl-2-ylmethyleneamine radical, which affords phenantridine (3) after ring closure. In contrast, the photolysis of 1 in methanol gives a high yield of benzotriazole (4).     

Synthesis of (4-nitro-1H-indol-6-yl)- and (4-amino-1H-indol-6-yl)phosphonic acid derivatives

Chemistry of Heterocyclic Compounds - A convenient methodology for the synthesis of previously unreported (1H-indol-6-yl)phosphonic acid derivatives has been described. Reaction of...     

Kinetics,catalysis, and mechanism of isomerization of N-[(benzotriazol-1-yl)methyl]anilines into the benzotriazol-2-yl derivatives

The ¹H NMR technique was applied for the measurement of the isomerization rates of N-ethyl-N-[(benzotriazol-1-yl)methyl]aniline ( 4 ) and 4-butyl-N-[(benzotriazol-1-yl)methyl]aniline ( 7 ) to the corresponding benzotriazol-2-yl isomers in dioxane-d₈ at 35°C. The rate constants obtained for pure dioxane-d₈ were 1.62 and 0.28 h^?1 for 4 and 7 , respectively. For both compounds, addition to acetic acid to the dioxane solutions accelerated the isomerizations whereas addition of triethylamine retarded it strongly. Addition of water slowed the isomerization of 4 but accelerated that of 7 : the different effects operating in the two cases are discussed and rationalized. © 1995 John Wiley & Sons, Inc.     

Synthesis of 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(2-cyclohexen-1-yl)- and 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(1-cyclohexen-1-yl)anilines

Alkenylation of 6-methyl-2-(2-cyclohexen-1-yl)- and 2-(1-cyclohexen-1-yl)anilines with piperylene in the presence of AlCl₃ and transformation of the resulting cyclohexenylanilines into carbazole structures were studied.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 441–443.Original Russian Text Copyright © 2005 by Gataullin, Ishberdina, Sotnikov, Abdrakhmanov.     

Syntheses and transformations of substituted benzazolyl- and tetrazolyl(benzotriazol-1-yl)methanes

Condensation reactions of o-hydroxy- and o-mercaptoanilines, and o-phenylenediamine with (benzotriazol-1-yl)acetic acid result in (1,3-benzazol-2-yl)(benzotriazol-1-yl)methanes. Cycloaddition of sodium azide to (benzotriazol-1-yl)acetonitrile leads to (1,2,3,4-tetrazol-5-yl)(benzotriazol-1-yl)methane. The diazolo-substituted benzotriazolylmethanes thus obtained were mono- and di-alkylated at the methylene group and the displacement of the benzotriazole group by nucleophiles was investigated.     

Azoles as Suzuki cross-coupling leaving groups: syntheses of 6-arylpurine 2'-deoxynucleosides and nucleosides from 6-(imidazol-1-yl)- and 6-(1,2,4-triazol-4-yl)purine derivatives

[reaction: see text] 6-(Imidazol-1-yl)-, 6-(benzimidazol-1-yl)-, and 6-(1,2,4-triazol-4-yl)purine nucleosides undergo a nickel-mediated C-C cross-coupling of azole-substituted purine derivatives with arylboronic acids to give good yields of 6-arylpurine nucleosides.     

Synthesis of stereoisomeric 4-(2-methylindolin-1-yl)- and 4-(2-methylindol-1-yl) derivatives of glutamic acid

The reaction of dimethyl (2S,4RS)-N-phthaloyl-4-bromoglutamate with 2-methylindoline afforded diastereomeric 4-(2-methylindolin-1-yl)-(S)-glutamic acid derivatives, whose oxidation gave rise to 4-(2-methylindol-1-yl)-(S)-glutamic acid derivatives.     

2-（1H-咪唑-1-基）-1-（2，3，4-三甲氧基）苯乙酮肟酯新化合物合成与生物活性研究

首次合成了12个2-（1H-咪唑-1-基）-1-（2，3，4-三甲氧基）苯乙酮肟酯新 化合物，并经元素分析、红外光谱、核磁共振氢谱对其结构进行了表征，初步生物 活性测试表明，有些化合物具有杀菌活性。研究了这些新化合物结构与光谱特征之 间的关系。     

Synthesis and reactivity of 2-(benzothiazol-2-yl)-1-bromo-1,2-ethanedione-1-arylhydrazones

The novel, highly versatile 2-(benzothiazol-2-yl)-1-bromo-1,2-ethanedione-1-arylhydrazones 3 were prepared and their behavior toward some nucleophiles was investigated. Thus, reaction of 3 with the sodium salt of malononitrile afforded the aminopyrazolecarbonitriles 5 that undergo cyclocondensation with hydrazine, formic acid, and formamide to give the corresponding pyrazolo[3,4-d]pyridazine 6, pyrazolo[3,4-d]pyrimidinone 7, and pyrazolo[3,4-d]pyrimidine 8 derivatives, respectively. Similarly, reactions of 3 with each of acetylacetone, dibenzoylmethane, and benzoylacetonitrile afforded the corresponding pyrazole derivatives 9, 10, and 11, respectively. The latter products undergo cyclocondensation with hydrazine to afford the corresponding pyrazolo[3,4-d]pyridazines 12, 13, and 14, respectively. © 1997 John Wiley & Sons, Inc.     

Synthesis of 1-(pyridin-4-yl)-3,6-diazahomoadamantane and its derivatives

Condensation of 1-(pyridin-4-yl)propan-2-one with 1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane gave 1-( pyridin-4-yl)-3,6-diazahomoadamantan-9-one as intermediate product in the synthesis of 1-(pyridin-4-yl)-3,6-diazahomoadamantane and its derivatives having functional substituents at the bridging carbon atom in the homoadamantane skeleton.     

1-芳基亚甲基-2-(6-(3,5-二甲基-1H-吡唑-1-基)-1,2,4,5-四嗪-3-基)肼的合成及抗菌活性

以水合肼和硝酸胍为原料,经过环合、氧化和肼化,得到3-(3,5-二甲基-1H-吡唑-1-基)-6-肼基-1,2,4,5-四嗪(4),以此为原料和不同芳香醛发生腙化反应,得到系列1-芳基亚甲基-2-(6-(3,5-二甲基-1H-吡唑-1-基)-1,2,4,5-四嗪-3-基)肼(5),产物经元素分析、1H NMR、IR和MS表征。所合成的系列化合物抗菌活性测试表明,它们对大肠杆菌、金黄色葡萄球菌、枯草杆菌等3种细菌表现出一定程度的抑制活性。     

Spectroscopic studies on binding of 1-phenyl-3-(coumarin-6-yl)sulfonylurea to bovine serum albumin

The interaction of 1-phenyl-3-(coumarin-6-yl)sulfonylurea (SU22) with bovine serum albumin (BSA) has been investigated by fluorescence quenching spectroscopy combined with UV-absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy techniques under simulative physiological conditions for the first time. Fluorescence data and UV-absorption spectra revealed that the quenching mechanism of fluorescence of BSA by SU22 was a static quenching process and the number of binding sites was about 0.8858; the thermodynamic parameters (DeltaG=-29.23 kJ mol(-1), DeltaH=-47.48 kJ mol(-1), and DeltaS=-61.24 J mol(-1)K(-1)) explained that hydrogen bond and Van der Waals interaction were the main binding force stabilizing the complex. The binding average distance between SU22 and BSA was obtained (3.20 nm) on the basis of the F?rster's theory. In addition, The CD spectra and FT-IR spectra have proved that BSA secondary structure changed in the presence of SU22 in aqueous solution.