Nucleosides imidazole

Several stereoselective syntheses of 4-(ribofuranosyl)imidazole nucleosides were reported. Imidazole 53 was obtained from 50 by a Mitsunobu cyclization [95TL3165]. Treatment of a suitably protected ribofuranosyl chloride with two equivalents of a lithioimidazole afforded the 1-(5-imidazolyl)ribofuranoid glycal (54) directly which undergoes elimination to the furylimidazole (55) [95CPB152]. 

Almost all recorded purine syntheses from imidazoles involve the cyclization of 5(4)-aminoimidazole-4(5)-carboxylic acid derivatives especially the carboxamides, thiocar-boxamides, carboxamidines, carboxamidoximes, nitriles and esters. The intermediates used for completion of the purine ring are much the same as have been used for Traube cyclization of diaminopyrimidines (Section 4.09.7.3), especially formic and carbonic acid derivatives, and cyclization generally occurs-under much milder conditions. This feature has been of special value in the synthesis of purine nucleosides from imidazole nucleoside precursors. The resultant purine will have variable substituents at C-2 and C-6 and it is convenient to discuss and classify the various preparations largely in terms of the introduced 2-substituents. The C-6 substituents largely reflect the type of carboxylic acid moiety used and do not vary very much between amino, oxo and thioxo. 

Nucleobase anion glycosylation of 6-substituted purines yields the jV -nucleosides as the main products. The situation changes if 5-aminoimidazole-4-carbonitrile instead of a purine is used as a precursor, then 4-amino-l-(ribofuranosyl)imidazole-5-carbonitrile (AICN-riboside) is formed as the main product and the N3 regioisomer as a minor component. For this reason imidazole nucleosides are very useful intermediates, especially for the synthesis of N7 glycosylated purines,... 

DisulfanyT7-(2, 3, 5 -tri-0-acetyl-)S-D-ribofuranosyl)purine (2) has been prepared by ring closure of an imidazole nucleoside with carbon disulfide in pyridine. ... 

The above process has been adapted to high-yielding synthesis of some C-5-linkcd imidazole nucleosides [23]. 

Strepikheev, Y.A., Khokhlov, P.S., and Kashemirov, B.A., Synthesis of oximinocyanomethylphospho-nates, Zh. Obshch. Khim., 51, 1206. 1981 Gen. Chem. USSR (Engl. Transl.), 51, 1020, 1981. Buchanan, J.G., McCaig, A.E., and Wightman, R.H., The synthesis of 4-alkylsulphonyl-5-amino- and 5-amino-4-phosphono-imidazole nucleosides as potential inhibitors of purine biosynthesis, J. Chem. Soc., Perkin Trans. 1, 955, 1990. 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

Lithiation at the 5-position is possible when C-2 is blocked, a reaction of use in introducing functionality to imidazole nucleosides (Equation (34)) <87CPB4056>. When the 2-position is blocked by trialkylsilyl, however, 5-deprotonation becomes more difficult with i-butyllithium the reagent of... 

Treatment of the silver salt of methyl imidazole-4,5-dicarboxylate (138) with acylglycopyranosyl halides gave the imidazole nucleosides (139) which, on reaction with ammonia, were deblocked and converted to the diamides (140). Reaction of the diamides (140) with alkaline hypobromite (the Hofmann reaction) gave mixtures of the 7- and 9-nucleosides (141 and 142), with the 9-isomer predominating. In fact, in the early investiga-tions- of this reaction, only the 9-isomer w as isolated but, in the preparation of 8-azapurine nucleosides by the same method,both... 

The naturally occurring nucleoside analogues discussed in this section contain the IV-glycosyl linkage and either purine, pyrimidine, imidazole, diazepin, or indole rings. The purine nucleosides inhibit protein synthesis, RNA and DNA synthesis, and methyltransferases they have antimycoplasmal, antiviral, hypotensive, antifungal, antimycobacterial, and antitumor activities and induce sporulation (1—4). The pyrimidine nucleosides inhibit protein synthesis, virus replication, RNA and DNA synthesis, and cAMP phosphodiesterase. The imidazole nucleosides inhibit nucleic acid synthesis. The diazepin nucleosides inhibit adenosine deaminase (ADA). The indole nucleosides inhibit bacteria, yeast, fungi, and viruses. 

The chemistry and biochemistry of polyoxins has been discussed. The structure of the neopolyoxins A, B, and C, which are potent inhibitors of fungal cell-wall chitin synthetase, has been established neopolyoxins A and B are the imidazole nucleosides (18) and (19), respectively, whereas neopolyoxin C is the corresponding uracil-1-yl nucleoside the structure of polyoxin N was also revised, the amino-acid side-chain of (18) being replaced by 2-amino-5-(9-carbamoyl-2-deoxy-L-xyIonic acid. The new antibiotic nikkomycin B also has the structure of (18), although its stereochemistry has not been fully established. Adenomycin has... 

Full details of the synthesis of adenine and imidazole nucleosides of d-mannofuranose from 2,3 5,6-di-O-isopropylidene-D-mannofuranosylamine have now appeared (see Vol. 11, p. 171). The same group has also synthesized the arabinofuranosyl 5-aminoimidazole-4-carboxylate (14) by condensation of 2,3,5-tri-O-benzyl a-D-arafemo-furanosyl chloride with the parent base followed by hydrogenation. 1,3-Dipolar cycloaddition of glycosyl azides to 1,4-naphthoquinone or 2-methyl-1,4-benzoquinone gave the nucleosides (15), (16), and (17), which were shown to exhibit some cytostatic activity... 

A number of nucleosides have been elaborated from glycosylamine derivatives for example, imidazole nucleosides have been obtained by the routes outlined in Schemes 121 and 122, and l-jS-D-ribopyranosylisatin was obtained by deacetylation of the product resulting from the action of oxalyl chloride on N-(2,3,4-tri-0-acetyl-j8-D-ribopyranosyl)aniline. Glycosylhydrazines, which exist as equilibrium mixtures of acyclic and cyclic forms, have also been used to prepare ribonucleosides (Scheme 123). A new synthesis of 9-j8-D-arabinofuranosyl-adenine (369) is shown in Scheme 124. ... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

The imidazole nucleoside derivative (31) has been used to prepare... 

Various nucleosides of 5,5-disubstituted barbituric acid and 4-alkoxy-6(iH)-pyrimidones have been reported. Several indole nucleosides were synthesized , and a review was published on imidazole nucleosides and nucleotides. The structure of the antibiotic showdomycin XIV was established as 2-(6-D-ribofuranosyl)maleimide, toe., a "C-nucleoside" related to uridine 73, iwo other "C-nucleosides", 1-deazuridine and 2 -deoxy-l-deazauridine, were synthesized analogously to pseudouridine however, these conq>ounds were highly labile. ... 

Although purine nucleosides can frequently be halogenated at the vacant imidazole carbon (see above), AMialogenosuccinimides in acetic acid tend to promote intramolecular cyclizations instead. It has been demonstrated that 2-bromoadenosine is not an intermediate in this process (Scheme 55), which is believed to involve initial attack by positive halogen at N-3. 

---