- Nucleosides from Carbohydrate Adducts of Diaminomaleonitrile. A Novel Synthesis of 5-Amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide and 5-Amino-1-(β-D-ribopyranosyl)imidazole-4-carboxamide
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The stereospecific and regiospecific synthesis of 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (16) was achieved in six steps.A key intermediate in the synthesis, N-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)diaminomaleonitrile (3), was prepared by two routes: the reaction of diaminomaleonitrile (1) with 1-bromo-2,3,5-tri-O-benzoyl-β-D-ribofuranose (2) and the reaction of the bis(trimethylsilyl) derivative of diaminomaleonitrile (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (5).Reaction of 3 triethyl orthoformate yielded 4,5-dicyano-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole (10).Alternatively 10 was synthesized by the acid-catalyzed cyclization of the N-formyl derivative 12 which was prepared by the reaction of the trimethylsilyl derivative of N-formyldiaminomaleonitrile 11 with 5.Deblocking 10 with 1 equiv of sodium methoxide at room temperature resulted in the regiospecific formation of the 5-imidate 14.Reaction of 14 with alkaline hypochlorite yielded 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carbonitrile (15) by a Hofmann rearrangement.Alkaline hydrolysis of the nitrile function yielded the corresponding amide 16. 5-Amino-1-(β-D-ribopyranosyl)imidazole-4-carboxamide (28) was prepared by a similar synthetic sequence.Reaction of diaminomaleonitrile (1) with ribose gave a mixture of the α- and β-anomers of D-ribopyranosyldiaminomaleonitrile (17).Compound 17 was converted to a mixture of the anomeric tri-O-acetates which on heating with triethyl orthoformate gave a separable mixture of the α- and β-anomers of 4,5-dicyano-1-(2',3',4'-tri-O-acetyl-D-ribopyranosyl)imidazole (19 and 20, respectively).Reaction of 19 with NH3/CH3OH at room temperature cleaved the three acetyl groups and regiospecifically converted the 5-cyano to the 5-imidate (26).The regiospecificity is due to the attack of the 2'-oxy anion on the 5-cyano group as shown by the isolation of the cyclic imidate 25 when the reaction is carried out at 0 deg C.The Hofmann rearrangement of imidate 26 followed by alkaline hydrolysis gave 5-amino-1-(β-D-ribopyranosyl)imidazole-4-carbonitrile 27 and 28, respectively.The 1H and 13C NMR spectra of imidates 14 and 26 have multiple peaks for the protons and carbons, respectively.Restricted rotation of the 5-imidate (energy of activation 18 kcal) results in isomers of 14 and 26 with different NMR spectra.The C-2, H-1' coupling constants of 2.5-3.1 Hz of the isomeric species comprising imidates 14 and 26 are consistent with a H-2, H-1' dihedral angle of 135 deg and an anti orientation of the imidazole with respect to the ribose ring; a conclusion confirmed by NOE measurements.
- Ferris, James P.,Devadas, Balekadru,Huang, Chun-Hsien,Ren, Wu-Yen
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p. 747 - 754
(2007/10/02)
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- Purines, Pyrimidines and Imidazoles. Part 55. Some D-Lyxofuranosyl Imidazoles Related to Intermediates in Purine Nucleotide de novo biosynthesis.
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Ethyl 5-N-acetylamino-1-(2,3:5,6-di-O-isopropylidene-α- and -β-D-mannofuranosyl)imidazole-4-carboxylates prepared by acetylation of the corresponding 5-amino derivatives and methanolysis of the mixture of 5-N-mono- and di-acetylaminoimidazoles produced were converted by aqueous acetic acid into ethyl 5-N-acetylamino 1-(2,3-O-isopropylidene-α- and β-D-mannofuranosyl)imidazole-4-carboxylates which with sodium periodate followed by sodium borohydride gave ethyl 5-N-acetylamino-1-(2,3-O-isopropylidene-α- and -β-D-lyxofuranosyl)imidazole-4-carboxylates.The configurations assigned to the anomeric lyxone nucleosides were confirmed by comparison of specific rotations of glycerol derivatives produced by periodate oxidation of the deacetonated nucleosides with that from an analogous ribose derivative, and by n.m.r. and c.d. studies.Products of acylation of several aminoimidazoles with trifluoroacetic anhydride and acetyl chloride are also described.
- Mackensie, Grahame,Shaw, Gordon
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p. 3201 - 3228
(2007/10/02)
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