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1.
Steven G. Wood N. Kent Dalley Rose D. George Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(2):187-194
Abstract The first chemical synthesis of 3-amino-1-β-D-ribofuranosyl-s-triazolo[5,1-c]-s-triazole (6) is described. Direct glycosylation of 3-amino-5(7)H-s-triazolo[5,1-c]-s-triazole (2) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose (3) in the presence of TMS-triflate gave 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-s-triazolo[5, 1-c]-s-triazole (4) which, on ammonolysis, gave 6. The absolute structure of 6 is determined by X-ray diffraction techniques employing Mo Kα radiation. The structure is solved by direct methods and refined to the R value of 0.044 by using a full-matrix least-squares method. The sugar of 6 has a 3T2 configuration. The torsion angles about the C5′–C4′ bond are both gauche and the torsion angle about the glycosidic bond is in the anti range. Each azole ring of the aglycon is planar and the dihedral angle between the planes of the rings is 3.6°. 相似文献
2.
Jack D. Anderson Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(5):853-863
Abstract The synthesis of pyrazolo[3,4-d]pyrimidine ribonucleoside 3′, 5′-cyclic phosphates related to cAMP, cIMP and cGMP has been achieved for the first time. Phosphorylation of 4-amino-6-methylthio-1-β-D-ribo-furanosylpyrazolo[3,4-d]pyrimidine (1) with POCl3 in trimethyl phosphate gave the corresponding 5′-phosphate (2a). DCC mediated intramolecular cyclization of 2a gave the corresponding 3′, 5′-cyclic phosphate (3a), which on subsequent dethiation provided the cAMP analog 4-amino-1-β-D-ribofuranosylpyrazolo[3, 4-d]pyrimidine 3′, 5′-cyclic phosphate (3b). A similar phosphorylation of 6-methylthio-1-β-D-ribofuranosylpyrazolo[3, 4-d]pyrimidin-4(5H)-one (5), followed by cyclization with DCC gave the 3′, 5′-cyclic phosphate of 5 (9a). Dethiation of 9a with Raney nickel gave the cIMP analog 1-β-D-ribofuranosylpyrazolo[3, 4-d]pyrimidin-4(5H)-one 3′, 5′-cyclic phosphate (9b). Oxidation of 9a with m-chloroperoxy benzoic acid, followed by ammonolysis provided the cGMP analog 6-amino-1-β-D-ribofuranosylpyrazolo [3, 4-d] pyrimidin-4(5H)-one 3′, 5′-cyclic phosphate (7). The structural assignment of these cyclic nucleotides was made by UV and H NMR spectroscopic studies. 相似文献
3.
Naeem B. Hanna Krishna G. Upadhya Charles R. Petrie Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(4):343-362
Abstract The synthesis of several 5′-substituted derivatives of ribavirin (1) and tiazofurin (3) are described. Direct acylation of 1 with the appropriate acyl chloride in pyridine-DMF gave the corresponding 5′-O-acyl derivatives (4a-h). Tosylation of the 2′, 3′-O-isopropylidene-ribavirin (6) and tiazofurin (11) with p-toluenesulfonyl chloride gave the respective 5′-O-p-tolylsulfonyl derivatives (7a and 12a), which were converted to 5′-azido-5′-deoxy derivatives (7b and 12b) by reacting with sodium/lithium azide. Deisopropylidenation of 7b and 12b, followed by catalytic hydrogenation afforded 1-(5-amino-5-deoxy-β-D)-ribofuranosyl)-1, 2, 4-triazole-3-carboxamide (10b) and 2 - (5 -amino- 5-deoxy- β-D-ribofuranosyl) thiazole-4-carboxamide (16), respectively. Treatment of 6 with phthalimide in the presence of triphenylphosphine and diethyl azodicarboxylate furnished the corresponding 5′-deoxy-5′-phthaloylamino derivative (9). Reaction of 9 with n-butylamine and subsequent deisopropylidenation provided yet another route to 10b. Selective 5′-thioacetylation of 6 and 11 with thiolacetic acid, followed by saponification and deisopropylidenation afforded 5′-deoxy-5′-thio derivatives of 1-β-D-ribofuranosyl-1, 2, 4-triazole-3-carboxamide (8a) and 2-β-D-ribofuranosylthiazole-4-carboxamide (15), respectively. 相似文献
4.
Abstract Treatment of D-xylose (1) with 0.5% methanolic hydrogen chloride under controlled conditions followed by benzoylation and acetolysis afforded crystalline 1-O-acetyl-2, 3, 5-tri-O-benzoyl-α-D-xylofuranose (4) in good yield. Coupling of 4 with 2, 4-bis-trimethylsilyl derivatives of 5-alkyluracils (methyl, ethyl, propyl and butyl) (5a-5d), 5-fluorouracil (5e) and uracil (5f) in acetonitrile in the presence of stannic chloride gave 1-(2,3,5-tri-O-benzoyl-β-D-xylofuranosyl)-nucleosides (6a-6f). Saponification of 6 with sodium methoxide afforded 1-β-D-xylofuranosyl-5-substituted uracils (7a-7f). Condensation of 4 with free adenine in similar fashion and deblocking gave carcinostatic 9-β-D-xylofuranosyladenine (7g). 相似文献
5.
Yogesh S. Sanghvi Naeem B. Hanna Steven B. Larson Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(4):761-774
Abstract A synthesis of 1-(2,3-dideoxy-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (2′,3′-dideoxyribavirin, ddR) is described. Glycosylation of the sodium salt of 1,2,4-triazole-3-carbonitrile (5) with 1-chloro-2-deoxy-3,5-di-0-p-toluoyl-α-D-erythro-pentofuranose (1) gave exclusively the corresponding N-1 glycosyl derivative with β-anomeric configuration (6), which on ammonolysis provided a convenient synthesis of 2′-deoxyribavirin (7). Similar glycosylation of the sodium salt of methyl 1,2,4-triazole-3-carboxylate (2) with 1 gave a mixture of corresponding N-1 and N-2 glycosyl derivatives (3) and (4), respectively. Ammonolysis of 3 furnished yet another route to 7. A four-step deoxygenation procedure using imidazolylthiocarbonylation of the 3′-hydroxy group of 5′-0-toluoyl derivative (9a) gave ddR (11). The structure of 11 was proven by single crystal X-ray studies. In a preliminary in vitro study ddR was found to be inactive against HIV retrovirus. 相似文献
6.
Ganesh D. Kini William J. Hennen Roland K. Robins 《Nucleosides, nucleotides & nucleic acids》2013,32(3):581-587
Abstract A new, facile synthesis of 7-methyl-8-oxoguanosine is reported. 2-Chloro-7-methylpurine-6, 8-dione (5) was silylated with hexamethyldi-silazane and the silylated intermediate, 6, glycosylated with 1-0-acetyl-2, 3, 5-tri-0-benzoyl-D-ribofuranose to yield 2-chloro-7-methyl-9-(2′, 3′,-5′-tri-0-benzoyl-β-D-ribofuranosyl) purin-6, 8-dione (8). Deprotection of 8 with sodium hydroxide in aqueous methanol gave 2-chloro-7-methyl-9-(β-D-ribofuranosyl) purine-6,8-dione (9), which was aminated with liquid ammonia or methanolic ammonia to yield 7-methyl-8-oxoguanosine (3). 相似文献
7.
M. Bueno Martínez E. Román Galán J. A. Galbis Pérez 《Nucleosides, nucleotides & nucleic acids》2013,32(2):227-244
Abstract Fusion of 2-trimethylsilylpyridine and tetra-O-acetyl-aldehydo-D-xylose or 2,3:4,5-di-O-isopropylidene-aldehydo-L-arabinose led, after removing of the protecting groups, to 2-(pentitol-1-yl)pyridines of D-gulo and D-ido or L-manno configurations. Dehydration of the sugar-chain with D-gulo and D-ido configurations gave the corresponding 2′,5′-anhydro derivatives, whereas 2-(5-O-isopropyl-L-manno-pentitol-1-yl)-pyridine was the only compound formed by dehydration of the sugar-chain with L-manno configuration. Structural proofs are based on 1H and 13C NMR spectra. 相似文献
8.
Julia Castro-pichel Ma. Teresa García-López Rosario Herranz Concepción Pérez 《Nucleosides, nucleotides & nucleic acids》2013,32(7):985-1000
Abstract 5′-O-[N-(Aminoacyl)sulfamoyl]-uridines and -thymidines 4a-12a and 4b-12b have been synthesized and tested against Herpes Simplex virus type 2 (HSV-2) and as cytostatics. Condensation of 2′,3′-O-isopropylidene-5′-O-sulfamoyluridine and 3′-O-acetyl-5′-O-sulfamoylthymidine with the N-hydroxysuccinimide esters of Boc-L-Ser(Bzl), (2R, 3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbuta-noic acid [(2R, 3S-N-Z-AHPBA], (2R, 3S) and (2S, 3R)-N-Boc-AHPBA gave 4a,b-7a,b, which after removal of the protecting groups provided 1Oa,b-12a,b. A study of the selective removal of the O-Bzl protecting group from the L-Ser derivatives 4a,b, without hydrogenation of the pyrimidine ring, has been carried out. Only the fully protected uridine derivatives 4a-7a did exhibit high anti-HSV-2 activity, and none of the synthesized compounds showed significant cytostatic activity against HeLa cells cultures. 相似文献
9.
Tomokazu Sugawara Toyoaki Ishikura Tokuo Itoh Yoshihisa Mizuno 《Nucleosides, nucleotides & nucleic acids》2013,32(3):239-251
Abstract 9-β-D-Arabinofuranosyldeazaadenines [1-deaza-araA (4a) and 3-deaza-araA (4b)] were prepared from 6-chloro-β-D-ribofuranosyl-1- (6a) and -3-deazapurine (6b), respectively. Synthesis of 2′-deoxy-1-deaza-adenosine (5a) from 1-deazaadenosine (6c) is also described. 相似文献
10.
Giin-Yuan Shen Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1707-1717
Abstract The syntheses of all three of the mono-N-methy1 derivatives of C-ribavirin (3-β-D-ribofuranosyl-1, 2, 4-triazole-5-carboxamide, 2) have been accomplished. Reaction of 1-(β-D-ribofuranosyliminomethyl)-2-methyl-hydrazine ( 7 ) with ethyl oxamate (8) in boiling ethanol gave the N′-methyl-C-ribavirin ( 3 ). A similar treatment of β-D-ribofuranosyl-1-carboximidic acid methyl ester ( 6 ) with N′-methyloxamic hydrazide ( 10 ) furnished the N2-methyl-C-ribavirin ( 4 ). Direct methylation of unprotected 2 with methyl iodide in the presence of potassium carbonate in dimethyl sulfoxide gave N 4-methyl isomer ( 5 ) as the major product. Structural assignments of 3 , 4 , and 5 were based on the unequivocal synthetic sequences, 1H and 13C NMR data and confirmed by single crystal X-ray diffraction analysis. 相似文献
11.
Abstract The facile synthesis of several substituted carbohydrates that are amenable for the preparation of 2′,3′-dideoxy-3′-hydroxymethyl nucleosides are reported. Elaboration of a previously reported analog, 5-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-1,2-O-isopropylidene-β-D- ribofuranose (4) has provided two 2,3-dideoxy-3-branched ribose derivatives 5-O-benzoyl-2,3-dideoxy-3-(benzyloxy)methyl-1-O-methyl-β-D-ribofuranose (7) and 1.5-di-O-benzoyl-2,3-dideoxy-3-(benzyloxy)methyl-(α,β)-D-ribofuranose (10). Due to problems involved with the separation of anomeric mixtures when these carbohydrates were condensed with an heterocycle, another versatile synthon 5-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-2-O-t-butyldimethylslyl-1-O- methyl-β-D-ribofuranose (12) was synthesized. The utility of this compound (12) is demonstrated in the total synthesis of 1-[3-deoxy-3-hydroxymethyl-β-D-ribofuranosyl]thymine (20). 相似文献
12.
Abstract This report summarizes our results8 on how the determination of the thermodynamics of the two-state North (N, C2′-exo-C3′-endo) ? South (S,C2′-endo-C3′-exo) pseudorotational equilibrium in aqueous solution (pD 0.6 - 12.0) basing on vicinal 3JHH extracted from 1H-NMR spectra measured at 500 MHz from 278K to 358K yields an experimental energy inventory of the unique stereoelectronic forces that dictate the conformation of the sugar moiety in β-D-ribonucleosides (rNs), β-D-nucleotides, in the mirror-image β-D- versus β-L-2′-deoxynucleosides (dNs) as well as in α-D- or L- versus β-D- or L-2′-dNs. Our work shows for the first time that the free-energies of the inherent internal flexibilities of β-D- versus β-L-2′-dNs and α-D- versus α-L-2′-dNs are identical, whereas the aglycone promoted tunability of the constituent sugar conformation is grossly affected in the α-nucleosides compared to the β-counterparts. 相似文献
13.
Abstract 6-(3-methyl-2-butenylamino)-2-methylthio-9-(β-D-ribofuranosyl)purine (1) is a naturally occurring nucleoside with potent cytokinin activity. It has been isolated and identified in the t-RNA of E. coli,1,2 the t-RNA from wheat germ3,4 and from Staphylococcus epidermidis.5 In addition, compound 1 has been found in t-RNA species corresponding to each of six amino acids whose codons start with uridine, i.e., t-RNACys 相似文献
14.
Jun-ichi Asakura 《Nucleosides, nucleotides & nucleic acids》2013,32(7):701-711
Abstract Treatment of poly-acetyl or -benzoyl protected ribonucleosides (1a-i) and 2′-deoxyribonucleosides (3a-d) with metal carbonates such as NaHCO3 or Na2CO3 in MeOH gave the corresponding deacylated free ribomucleosides (2a-d and 4a-b) in excellent high yields. 相似文献
15.
J. Fuentes Mota J. I. Fernández García-Hierro P. Areces Bravo F. Rebolledo Vicente J. A. Galbis Pérez 《Nucleosides, nucleotides & nucleic acids》2013,32(4):457-477
Abstract 1-Methyl- and 1-aryl-(1,2-dideoxy-D-glyofurano)[2,1-d]-imidazolidine-2-thiones having the configurations β-D-glycero-L-gluco (4), β-D-glycero-D-ido (5—8), α-D glycerol-D-galacto (9—10) and β-D-glycero-D-talo (11, 12) are prepared by reaction of 2-amino-2-deoxy-aldoses with methyl and aryl isothiocyanates. 1-Aryl-(1,2-dideoxy–β-D-glycero-L-gluco-heptofurano)[2,1-d]imidazolidine-2-thiones (1—3) have been converted into 1-aryl-4-(D-galacto-pentitol-1-yl)-4-imidazo-line-2-thiones (24—26) by acid catalysed isomerization. 相似文献
16.
L. D. Hawkins J. C. Hanvey F. L. Boyd Jr. David C. Baker H. D. Hollis Showalter 《Nucleosides, nucleotides & nucleic acids》2013,32(5):479-494
Abstract Glycosylation of the heterocycle, 6,7-dihydro-imidazo [4,5-d] [1,3] diazepin-8(3H)-one, with suitably protected sugars under the influence of Lewis acid catalysts gave the β-D-ribo- and 3′-deoxy-β-D-erythropento-furanosyl nucleosides. Deprotection and reduction of the keto nucleosides with sodium borohydride gave the (8R)- and (8S)-3-β-D-glycofuranosyl-3,6,7,8-tetrahydroimidazo [4,5-d]-[1,3] diazepin-8-ols, the (8R)-isomers of which are potent inhibitors of adenosine deaminase. 相似文献
17.
Yogesh S. Sanghvi Krishna G. Upadhya N. Kent Dalley Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(4):737-759
Abstract Several 4-substituted-1-β-D-ribofuranosyl-3-hydroxypyrazoles were prepared as structural analogs of pyrazofurin. Glycosylation of the TMS derivative of ethyl 3(5)-hydroxypyrazole-4-carboxylate (3) with 1-0-acetyl-2,3,5-tri-0-benzoyl-D-ribofuranose in the presence of TMS-triflate gave predominantly ethyl 3-hydroxy-1-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)pyrazole-4-carboxylate (4a), which on subsequent ammonolysis furnished 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (5). Benzylation of 4a with benzyl bromide and further ammonolysis gave 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (8a). Catalytic (Pd/C) hydrogenation of 8a afforded yet another high yield route to 5. Saponification of the ester function of ethyl 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxylate (7b) gave the corresponding 4-carboxylic acid (6a). Phosphorylation of 8a and subsequent debenzylation of the intermediate 11a gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide 5′-phosphate (11b). Dehydration of 3-benzyloxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carboxamide (8b) with POCl3 provided the corresponding 4-carbonitrile derivative (10a), which on debenzylation with Cl3SiI gave 3-hydroxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carbonitrile (13). Reaction of 13 with H2S/pyridine and subsequent deacetylation gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-thiocarboxamide (12b). Similarly, treatment of 13 with NH2OH afforded 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamidoxime (14a), which on catalytic (Pd/C) hydrogenation gave the corresponding 4-carboxamidine derivative (14b). The structural assignment of these pyrazole ribonucleosides was made by single-crystal X-ray analysis of 6a. None of these compounds exhibited any significant antitumor or antiviral activity in cell culture. 相似文献
18.
José Fiandor María Teresa García-López Federico G. De las Heras Paloma P. Méndez-Castrillón Carmen Gil-Fernández Sara Pérez 《Nucleosides, nucleotides & nucleic acids》2013,32(2):257-271
Abstract A series of 5′-O-[[[[(alkyl)oxy]carbonyl] amino] sulfonyl] uridines have been synthesized by reaction of cyclohexanol, palmityl alcohol, 1,2-di-O-benzoylpropanetriol and 2,3,4,6-tetra-O-benzoyl-L-glucopyranose with chlorosulfonyl isocyanate and 2,3′-O-isopropylidene-uridine. Another series of 5′-O-(N-ethyl and N-isopropylsulfamoyl) uridines have been prepared by reaction of 2′,3′-O-isopropylidene and 2′,3′-di-O-acetyluridine with N-ethylsulfamoyl and N-isopropylsulfamoyl chlorides. All compounds were tested against HSV-2, VV, SV and ASFV viruses. 2′,3′-Di-O-acetyl-5′-O-(N-ethyl and N-isopropylsulfamoyl) uridine showed significant activities against HSV-2. 5′-O-[[[[(2,3,4,6-Tetra-O-benzoyl-β-L-glucopyranosyl)oxy]carbonyl]amino] sulfonyl]-2′,3′-O-isopropylideneuridine was very active against ASFV. 相似文献
19.
B. Azmy P. Fernández-resa P. Goya R. Nieves C. Ochoa M. Stud 《Nucleosides, nucleotides & nucleic acids》2013,32(4):325-337
Abstract Synthesis of methyl, glucosyl and ribosyl derivatives of 7-amino-2H, 4H-[1, 2, 3]triazolo [4, 5-c] [1, 2, 6] thiadiazine 5, 5-dioxide (1a) and 7-amino-4H- [1, 2, 5] thiadiazolo [3, 4-c][1, 2, 6] thiadiazine 5, 5-dioxide (2a) is described. The structures of the glycosyl derivatives are discussed on the basis of their PMR- and UV-spectroscopic data. 相似文献
20.
Mohammed A. E. Sallam 《Nucleosides, nucleotides & nucleic acids》2013,32(3):297-313
Abstract The C-nucleoside analogs 6,7-dimethyl-3-β-D-erythrofuranosyl-1-phenylpyrazolo[3,4-b]quinoxaline 4 and 3-β- D -erythrofuranosyl-1-p-fluorophenylpyrazolo[3,4-b]quinoxaline 8 were prepared by dehydration of the polyhydroxyalkyl chain of 6,7-dimethyl-1-phenyl-3-( D -arabino-tetritol-1-yl)-pyrazolo[3,4-b]quinoxaline 3 and 1-p-fluorophenyl-3-( D -arabino-tetritol-1-yl)-pyrazolo[3,4-b]quinoxaline 7, respectively. The structure and anomeric configuration of the products were determined by n.m.r. spectroscopy. The mass spectra and biological activities in connection with chemical constitution are discussed. 相似文献