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1.
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   

2.
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   

3.
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   

4.
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   

5.
Abstract

The syntheses and preliminary biological evaluation of several novel pyrrolo[3,2-d]pyrimidine and thieno[3,2-d]pyrimidine C-nucleosides incorporating the arabinofuranosyl or 2′-deoxyribofuranosyl sugar moiety are described. The 2′-deoxy thieno[3,2-d]pyrimidine C-nucleosides (15 and 16) were obtained from 7-(β-D-ribofuranosyl)-4-oxo-3H-thieno[3,2-d]pyrimidine (3) and its 4-SMe derivative 8. “2”-Deoxy-9-deazaadenosine (31), “9-Deaza ara-A” (38) and the 2′-substituted arabinosyl pyrrolo[3,2-d]pyrimidine C-nucleosides (42 - 44) were synthesized from 4-amino-7-(2,3-O-isopropylidene-5-O-trityl-β-D-ribofuranosyl)-5H-pyrrolo[3,2-d]pyrimidine (21)  相似文献   

6.
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   

7.
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   

8.
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   

9.
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   

10.
Abstract

The synthesis of pyrazolo[3,4-d]pyrimidine 2′-deoxyribo-nucleosides with various substituents at C-4 and C-6 (1 4) is described employing either liquid-liquid or solid-liquid phase-transfer glycosylation. From 1a (Z8C7Ad) and 2b (Z8C7Gd) the phosphoramidites 12a, b and 15a, b were synthesized. They were used in automated solid-phase synthesis resulting in the oligonucleotides 16 - 25. Deoxygenation (3′-OH) of 1a and 2b yielded pyrazolo[3,4-d]-pyrimidine 2′,3′-dideoxynucleosides isosteric to ddA, ddG, and ddI.  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

Acid catalyzed isomerization of 1-aryl-(1,2-dideoxy-D-glycero-β-L-gluco-heptofuranose) [1,2-d]-2-imidazolines (4) yields 1-aryl-4-(D-galacto-pentitol-1-yl)imidazoles (8) which can be also obtained by reductive desulphuration of 1-aryl-2-benzylthio-4-(D-galacto-pentitol-1-yl)imidazoles (6). Compounds (4) were obtained by desulphuration with Raney nickel from 1-aryl-(1,2-dideoxy-D-glycero-β-L-gluco-heptofuranose) [1,2-d]-imidazolidine-2-thiones (1) or 1-aryl-2-benzylthio-(1,2-dideoxy-D-glycero-β-L-gluco-heptofuranose) [1,2-d]-2-imidazolines (2).  相似文献   

13.
Abstract

A synthesis of 2,4-dideazaribavirin ( 2 ), brunfelsamidine ribonucleoside ( 8c ) and certain related derivatives are described for the first time using the stereospecific sodium salt glycosylation procedure. Glycosylation of the sodium salt of pyrrole-3-carbonitrile ( 4 ) with 1-chloro-2, 3-O-t-isopropylidene-5-O-t-butyldimethylsilyl-α-D-ribofuranose ( 5 ) gave exclusively the corresponding blocked nucleoside ( 6 ) with β-anomeric configuration, which on deprotection provided 1-β-D-ribofuranosylpyrrole-3-carbonitrile ( 7 ). Functional group tranformation of 7 gave 2 , 8c and related 3-substituted pyrrole ribonucleosides. These compounds are devoid of any significant antiviral/antitumor activity invitro.  相似文献   

14.
Abstract

The synthesis and antiherpetic activity of 9-[[[2-hydroxy-1-(hydroxymethyl)ethyl]thio]methy1]guanine (4) and 1-[[[2-hydroxy-1-(hydroxymethyl)ethyl]thio]methy]cytosine (6), the side-chain thio analogues of ganciclovir (3) and BW A1117U (5), are described. The sidechain synthon 1,3-bis(benzyloxy)-2-[(chloromethyl)thio]propane (11) was prepared in four steps from 1,3-bis(benzyloxy)-2-propanol (7). Alkylation of 2-amino-6-chloro-9H-purine with 11 provided the intermediate 9-substituted-2-amino-6-chloropurine 12, which was conveniently converted to 4 in two steps. Reaction of a fivefold excess of cytosine with 11 provided the desired 1-isomer 14, which was debenzylated to give 6. In contrast with ganciclovir (3) and BW A1117U (5), neither 4 nor 6 had significant in vitro activity against human cytomegalovirus.  相似文献   

15.
Abstract

The synthesis of The synthesis of 2-hydroxymethyl-5-[N2-(5′-carboxamido tetrazolyl)]-1,3-oxathiolane (6a and 6b) and 2-hydroxymethyl-5-[N2-(5′-aminotetrazolyl)]-1,3-oxathiolane (7a and 7b) is described. It involved the preparation of suitable 1,3-oxathiolane precursors via cyclocondensation between benzoyloxyacetaldehyde and 2-mercaptoacetaldehyde di-[2-methoxyethyl] acetal, followed by condensation of adequately substituted tetrazoles using trimethylsilyltriflate or titanium tetrachloride as acid catalysts. In a preliminary in vitro study these new tetrazole oxathiolane nucleoside analogues were found inactive against HIV-1 retrovirus.  相似文献   

16.
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   

17.
Abstract

A chemical synthesis is described for 5′-O-triphosphate-4N-[6-(-γ-aminopropylamidosuccinylamido)-hexyl]deoxycytidine (13), the substrate for synthesis of 5′-O-triphosphate deoxycytidine derivatives (17-19) labeled with biotin, fluorescein and photoreactive azide.  相似文献   

18.
Abstract

Methods are described for the synthesis of the α and β anomers of 7-D?ribofuranosylfuro[3,2-d]pyrimidines substituted at C-4 with either amino, oxo, thiono, or methylthio groups. The analogous 2,4-dithiono compounds are also described. The key steps involve the LDA-promoted cyclizations of the cyano ethers 3 and 14 to give, respectively, the substituted furan C-nucleosides A and 16. After separation of anomers, these compounds were subjected to a number of pyrimidine-ring-forming reactions to give the desired bicyclic C-nucleosides. The adenosine analogue 13 is markedly cytotoxic to mouse L1210 cells in vitro, and the inosine analogue 20 shows activity against the pathogenic protozoans Leishmania donovani and Trypanosoma gambiense.  相似文献   

19.
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   

20.
Abstract

4-Amino-6-methylthio-1-(3′-deoxy-β-D-ribofuranosyl)-1H-pyrazolo-[3, 4-d]pyrimidine (11) and 6-methylthio-4(5H)-oxo-1-(3′-deoxy-β-D-ribofuranosyl)-1H-pyrazolo[3, 4-d]pyrimidine (12) have been synthesized from 1, 2-di-O-acetyl-5-O-benzoyl-3-deoxyribofuranose (5) and 4, 6-bis (methylthio)-1H-pyrazolo-[3, 4-d]pyrimidine (6). in a convergent fashion. Structural proofs are based on MS, IR, 1H NMR, 13C NMR and elemental analyses.  相似文献   

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