Synthesis of 8-methyl-2-azainosine and related nucleosides

The synthesis of 6-methyl-7-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azainosine ( 2) ) and 6-methyl-7-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 5 ) by diazotization of 5-amino-1-(β-D-ribofuranosyl)-2-methylimidazole-4-carboxamide ( 1 ) and diazotization of 5-amino-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-methylimidazole-4-carboxamide ( 3 ), followed by deacetylation of the resulting compound 4 , is described. The preparation of 6-methyl-5-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one ( 10 ) and 6-methyl-5-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 11 ) by glycosylation of 6-methylimidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azahypoxanthine, ( 7) ) is also described. Structural assignments were made on basis of analytical and ¹H-nmr and uv spectral data.     

The synthesis of 3-deazapyrimidine nucleosides related to uridine and cytidine and their derivatives

Condensation of 2,4-bis(trimethylsilyloxy)pyridine ( 1 ) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2 ) gave 4-hydroxy-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 3 ). Deblocking of 3 gave 4-hydroxy-1-β-D-ribofuranosyl-2-pyridone (3′-deazauridine) ( 4 ). Treatment of 4 with acetone and acid gave 2′,3′-O-isopropylidene-3-deazauridine ( 6 ). Reaction of 4 with diphenylcarbonate gave 2-hydroxy-1-β-D-arabinofuranosyl-4-pyridone-O₂←2′-cyclonucleoside ( 7 ) which established the point of gylcosidation and configuration of 4 . Base-catalyzed hydrolysis of 7 gave 4-hydroxy-1-β-D-arabinofuranosyl-2-pyridone (3-deazauracil arabinoside) ( 12 ). Fusion of 1 with 3,5-di-O-p-toluyl-2-deoxy-D-erythro-pentofuranosyl chloride ( 5 ) gave the blocked anomeric deoxynucleosides 8 and 10 which were saponified to give 4-hydroxy-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazauridine) ( 11 ) and its α anomer ( 9 ). Condensation of 4-acetamido-2-methoxypridine ( 13 ) with 2 gave 4-acetamido-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 14 ) which was treated with alcoholic ammonia to yield 4-acetamido-1-β-D-ribofuranosyl-2-pyridone ( 15 ) or with methanolic sodium methoxide to yield 4-amino-1-β-D-ribofuranosyl-2-pyridone (3-deazacytidine) ( 16 ). Condensation of 13 and 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride ( 17 ) gave the blocked nucleoside 22 which was treated with base and then hydrogenolyzed to give 4-amino-1-β-D-arabinofuranosyl-2-pyridone (3-deazacytosine arabinoside) ( 23 ). Fusion of 13 with 5 gave the blocked anomeric deoxynucleosides 18 and 20 which were deblocked with methanolic sodium methoxide to yield 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazacytidine) ( 21 ) and its a anomer 19 . The 2′-deoxy-erythro-pentofuranosides of both 3-deazauracil and 3-deazacytosine failed to obey Hudson's isorotation rule but did follow the “quartet”-“triplet” anomeric proton splitting pattern in the ¹H nmr spectra.     

The robinson annulation of some medium ring size 2-hydroxymethylenecyclanones

The adducts formed from methyl vinyl ketone and the 2-hydromethylene derivatives of cyclooctane and cyclodecanone can be cyclised to spiroketones containing the same number of C atoms. The spiroketone from cyclooctanone possesses a single UV maximum at 227 nm; the cyclodecanone compound has a further absorption at ca 246 nm. The constitution and stereochemistry of the ketols produced from the adducts under mild cyclising conditions have been investigated.     

New synthesis of imidazole derivatives from cyanobenzenes

An efficient access to 4-aryl imidazole scaffolds is described in two steps and one operation. Cyanoaryl-imidazolines are easily obtained by a (3?+?2) heterocyloaddition involving cyanobenzenes as dipolarophiles and a non-stabilized azomethine ylide as an electron-rich 1,3-dipole. Oxidation of the crude mixture affords an efficient two-steps access to the corresponding imidazoles.     

Facile synthesis of optically active imidazole derivatives

Five optically active imidazole derivatives have been synthesized via a facile 4-step reaction sequence starting from commercially available and inexpensive N-Cbz amino acids. While microwave assisted condensation was unsuccessful, the condensation of the corresponding alpha-bromoketones with formamidine acetate in liquid ammonia was revealed to be a useful method for the synthesis of such imidazole derivatives. The derivatives thus prepared are structurally-related to histamine.     

Convenient synthesis of 4-trifluoromethyl-substituted imidazole derivatives

Mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates (1), obtained from the reaction of N-acyl-N-alkylglycines (2) with trifluoroacetic anhydride, react with ammonia to give 4-trifluoromethyl-3,4-dihydroimidazoles (3) in high yields. Dehydration of 3 gives 4-trifluoromethylimidazoles (4) in high yields. The novel ring transformation of 1 into 3 occurs via a regioselective attack of ammonia on the C-2 position of the ring.     

咪唑及其衍生物的合成研究进展

咪唑及其衍生物作为药物中间体,在生物学、医学、有机化学中占据重要位置.目前咪唑的合成方法主要包括Radziszewski法、Phillips法、溴乙醛法.咪唑衍生物的合成方法主要包括金属催化剂合成法、酸性催化剂合成法、离子液体催化剂合成法等.本文对咪唑及其衍生物的合成方法进行了总结与归纳,并阐述了各种方法的优缺点.     

The synthesis of imidazole-2-thione nucleosides

Ribosylation of the trimethylsilyl derivative ( 1b ) of imidazole-2-thione ( 1a ) using either stannic chloride or silver perchlorate as catalyst resulted in the formation of the acylated derivatives of 1-(β-D-ribofuranosyl)imidazole-2-thione ( 3c ) and 1,3-di-(β-D-ribofuranosyl)imidazole-2-thione ( 4c ) with the latter predominating ( 4c:3c , ca. 2:1 ). The diribosylated nucleoside 4c was shown to be the N,N-disubstituted product rather than the N,S-disubstituted product by ¹H nmr and ¹³C nmr spectroscopy. Employment of the iodine-catalyzed fusion procedure reversed the aforementioned product ratios and provided the monoriboside 3c in excellent yield. When the trimethylsilyl derivative ( 5b ) of 2-methylthioimidazole ( 5a ) was reacted with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2d ) in acetonitrile, the major product was 1,3-di-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-imidazole-2-thione ( 4b ). The formation of 4b in this reaction is thought to arise via the Hilbert-Johnson mechanism.     

Acyclic analogues of purine and imidazole nucleosides

Hydroxyl-protected derivatives of 1- and 3-(2-hydroxyethoxymethyl)imidazoles ( 4,5,7-10 ) have been prepared from 5-amino-4-carbamoylimidazoles ( 2 ). The protected derivatives were converted to acyclic analogues of imidazole nucleosides ( 6 ) or subjected to various cyclisation reactions leading to 9-(2-hydroxy-ethoxymethyl)-substituted 2-methyl-, 2-phenyl- and 2-azahypoxanthines ( 18,13 and 20 , respectively) and 1-methylguanine ( 28 ). For assignment of structures to isomeric imidazole and purine derivatives, ¹³C chemical shifts have been used.     

Lewis acid-promoted annulation of O-quinonediimines by allylstannane: a facile synthesis of quinoxaline derivatives

[reaction: see text] Lewis acid-promoted addition of allyltri-n-butylstannane to o-quinonediimines afforded tetrahydroquinoxaline derivatives or allylated amides depending on the nature of the substituent on imine nitrogen.     

N-oxides of adenosine-type nucleosides undergo pyrimidine ring opening and closure to give 5-amino-4-(1,2,4-oxadiazol-3-yl)imidazole derivatives

Treatment of acylated adenosine N-oxides with carboxylic anhydrides and thiophenol resulted in pyrimidine ring opening followed by exocyclic ring closure. Ammonolysis gave 5-amino-4-(5-substituted-1,2,4-oxadiazol-3-yl)-1-(beta-d-ribofuranosyl)imidazole derivatives, whereas iodine in methanol selectively unmasked the 5-amino group. Related flexible nucleoside analogues can be prepared from adenine-type precursors.     

Solid-phase synthesis of 1,2-benzophenazine and some fused imidazole derivatives

The solid-phase synthesis of 1,2-benzophenazine and various N-methylbenzimidazoles using o-diaminoarenes is very promising and permits the synthesis of 1-methyl-4,5-[b]naphtho-1H-imidazole, which could not be obtained by the condensation of o-diaminoarenes with paraformaldehyde using the standard liquid-phase method.M. V. Lomonosov Moscow State University, 119899, Moscow, Institute for Synthetic Polymer Materials, 117461, Moscow, and Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, 1424432, Moscow Oblast. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 672–674, May, 1996. Original article submitted April 3, 1996.     

Conformational restriction of nucleosides by spirocyclic annulation at C4' including synthesis of the complementary dideoxy and didehydrodideoxy analogues

The concept of spirocyclic restriction, when generically applied to nucleoside mimics, allows for the preparation of diastereomeric pairs carrying either a syn- or anti-oriented hydroxyl at C-5'. Reported herein are convenient synthetic routes to enantiomerically pure 1-oxaspiro[4.4]nonanes featuring fully dihydroxylated end products as well as congeners having dideoxy and didehydrodideoxy substitution patterns. Notable use is made of the capacity for introducing unsaturation in the furanose sector via phenylsulfenylation and the incorporation of uracil and thymine by way of their silylated derivatives under catalysis with stannic chloride.