23192-64-5Relevant academic research and scientific papers
High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
Bookser, Brett C.,Raffaele, Nicholas B.
, p. 173 - 179 (2007/10/03)
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
Purines. LXIV syntheses of 9-methyl-2-azaadenine 1-oxide, its O-methyl derivative, and 1-substituted 5-azidoimidazole-4-carboxamides
Saito,Asahi,Nakajima,Fujii
, p. 2263 - 2268 (2007/10/02)
Diazotization of 5-amino-N'-methoxy-1-methylimidazole-4-carboxamidine (4a) with NaNO2, in 1 N aqueous HCl was found to give the 1-methoxy-2-azaadenine derivative 8a · HI, which produced 5-azido-1-methylimidazole-4-carbonitrile (5a) on treatment with aqueous Na2CO3. The ribosyl analogue 5b, obtained from the riboside 4b by similar diazotization, was utilized for the synthesis of 5-azido-1-β-D-ribofuranosylimidazole-4-carboxamide (9b), a novel AICA riboside analogue. On heating in HCONMe2 at 700C for 10 min, 8a · HI yielded the 1-N-oxide 7a. Several reactions to transform the functional groups in 5a were also investigated.
A UNIQUE TRANSFORMATION OF 5-AMINO-N'-METHOXYIMIDAZOLE-4-CARBOXAMIDINES BY DIAZOTIZATION: SYNTHESIS OF THE 5-AZIDO ANALOGUE OF AICA RIBOSIDE
Saito, Tohru,Asahi, Yayoi,Nakajima, Satoshi,Fujii, Tozo
, p. 329 - 332 (2007/10/02)
Diazotization of 1-substituted 5-amino-N'-methoxyimidazole-4-carboxamidines (I) was found to give the 5-azidoimidazole-4-carbonitriles II through the 1-methoxy-2-azaadenine intermediates IV.The product IIb from the riboside Ib was utilized for the synthesis of 5-azido-1-β-D-ribofuranosylimidazole-4-carboxamide (Vb), a novel AICA riboside analogue.
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
Ferris, James P.,Devadas, Balekadru,Huang, Chun-Hsien,Ren, Wu-Yen
, p. 747 - 754 (2007/10/02)
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.
SYNTHESIS OF 2-FORMYLADENOSINE USING DIETHOXYACETONITRILE AS A SYNTHON
Murakami, Teiichi,Otsuka, Masami,Kobayashi, Susumu,Ohno, Masaji
, p. 1315 - 1319 (2007/10/02)
Diethoxyacetonitrile has been utilized for the effective synthesis of adenine derivatives as a synthon.Novel 2-formyladenine (2b) and 2-formyladenosine (5b) have been prepared in high yields starting from AICN (1) and AICNR (4b), respectively.
Production of 2,6-diaminonebularines
-
, (2008/06/13)
Compounds of the formula STR1 wherein R is phenyl which may be substituted; or their acid addition salts, are produced in good yield by reacting a compound of the formula STR2 wherein R1, R2 and R3, independently of one another, are hydroxyl which may be protected, which is prepared in 2 or 3 steps from 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide, with a compound of the formula STR3 wherein R has the same meaning as defined above and X is amino which may be substituted or lower alkylthio, and, if necessary subjecting the resulting compound to a treatment for removal of protective groups on its hydroxyls.
Production of 2,6-diaminonebularines
-
, (2008/06/13)
Compounds of the formula STR1 wherein R is a phenyl or cyclohexyl group which may be substituted by halogen, lower alkyl or lower alkoxy, or their acid addition salts, are produced in good yield by reacting a compound of the formula STR2 wherein R1, R2 and R3, independently of each other, are a hydroxyl group which may be proctected, which is prepared in 2 or 3 steps from 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide, with a compound of the formula wherein R has the same meaning as defined above and R4 is hydrogen or the same group as R, and, if necessary, subjecting the resulting compound to a treatment for removal of protective groups on its hydroxyl groups.
2,6-Diaminonebularines
-
, (2008/06/13)
Novel N2 -substituted phenyl-2,6-diaminonebularines of the formula STR1 wherein R1 is halogen, lower alkyl or lower alkoxy and R2 is hydrogen, halogen, lower alkyl or lower alkoxy, and their acid addition salts have excellent coronary vasodilator action.
