Asymmetric Synthesis of Cyclopropyl Carbocyclic Nucleosides

Abstract

A number of nucleosides have been synthesized as potential antiviral and antitumor agents.¹ More recently, various dideoxynucleosides have been synthesized and found to be potent anti-HIV agents.² As a part of our drug discovery program for the treatment of HIV and HBV, we have initiated to synthesize cyclopropyl carbocyclic nucleosides as potential antiviral agents. Several papers regarding the synthesis of cyclopropyl carbocyclic nucleosides have appeared in the literature.^3–5 However, they are all reported as racemic mixtures. In this abstract, we wish to report the asymmetric synthesis of cylopropyl carbocyclic nucleosides from optically active common intermediates, 6 and 11.     

Urinary Modified Nucleosides as Tumor Markers

Abstract

Extracts of urinary nucleosides have been sequentially purified and examined by mass spectrometric analysis. Seventeen modified nucleosides have been unequivocally identified and a further five provisionally identified. While several nucleosides were found only in a small number of extracts, the occurrence and levels of others were found to correlate with the tumour type and stage.     

Synthesis and Testing of New Modified Nucleosides

Abstract

New efficient routes for the high-yielding synthesis of several classes of modified nucleosides have been developed. We have prepared both the D- and L-enantiomers of the methylene-expanded oxetanocin isonucleosides 1a-c and the L-2′,3′-dideoxy isonucleosides 2abc (both the oxa and thia analgoues) as well as new routes for the preparation of L-ribose and 2-deoxy L-ribose 3ab and their modified nucleosides 4.     

Synthesis and Antiviral Activities of Enantiomeric 1-[2-(Hydroxymethyl) Cyclopropyl] Methyl Nucleosides

Abstract

Cyclopropyl carbocyclic nucleosides have been synthesized from the key intermediate 2 which was converted to the mesylated cyclopropyl methyl alcohol 3. Condensation of compound 3 with various purine and pyrimidine bases gave the desired nucleosides. All synthesized nucleosides were evaluated for antiviral activity and cellular toxicity. Among them adenine 22 and guanine 23 derivatives showed moderate antiviral activity against HIV-1 and HBV. None of the other compounds showed any significant antiviral activities against HIV-1, HBV, HSV-1 and HSV-2 in vitro up to 100μM.     

8-Substituted Adenine β-D-Xylofuranosides and α-L-Arabinofuranosides

Abstract

9-(β-D-Xylofuranosyl) adenine and 9-(α-L-arabinofuranosyl)-adenine have been modified to give a series of 8-amino-substituted nucleosides. Convenient methods of halogenation of these nucleosides and reactions of 8-halogenated nucleosides with various amines are described. No significant cytotoxic or antiviral activity was found.     

Synthesis of Non-Natural Pyrimidine Nucleosides

Abstract

Two new non-natural nucleosides bearing an amide (8) or an amidine (9) function have been synthesized. Their properties and the geometry of the exocyclic double bond have been studied.     

Enzyme Aided Regioselective Acylation of Nucleosides

Abstract

Selective protection of the three hydroxyl groups of sugar moiety of nucleosides have been studied by enzyme-catalyzed esterification in organic solvents. Selectively protected products were obtained. The reaction provides an efficient method for selective protection of nucleosides.     

Carbocyclic Nucleosides: Synthesis of Analogues of Cyclobut-G

Abstract

Several carbocyclic nucleosides structurally related to Cyclobut-G have been synthesized from pinonic acid.     

Synthesis of 3′-Amino and 5′-Amino Hydantoin 2′-Deoxynucleosides

Abstract

3′-Amino and 5′-amino derivatives of hydantoin 2′-deoxynucleosides have been prepared from the corresponding 3′-phthalimido and 5′-azido nucleosides, respectively, which in turn were prepared by condensation of appropriate sugars with 5-benzylidenehydantoin. The amino nucleosides were tested for their potential activity against HIV and HSV.     

Enzymic Phosphorylation of Some 5-Aminoimidazole Nucleosides to the 5′-Phosphates

Abstract

Phosphotransferases from wheat shoots and a suitable phosphate donor have been used for the specific conversion of unprotected pyrimidine and purine nucleosides and some analogues into nucleoside 5'-phosphates. We have been interested to investigate the application of this technique to the phosphorylation of 5-aminoimidazole nucleosides to afford corresponding 5'-phosphates related to intermediates in purine nucleotide de novo biosynthesis. Several D-ribofuranosyl, D-xylofuranosyl and D-arabinofuranosyl 5-aminoimidazoles have been successfully phosphorylated (TABLE) to 5'-phosphates using a phosphotransferase from wheat shoots and p-nitrophenylphosphate as a phosphate donor.     

Nucleosides and Nucleotides. 98. Synthesis and Antitumor Activities of 5-Ethynylimidazole-4-carboxamide and -carbonitrile Derivatives

Abstract

5-Ethynyl-1-(2-deoxy-β-D-ribofuranosyl)imidazole-4-carbonitrile (4) and -carboxamide (5) and 5-ethynyl-1-(5-deoxy-β-D-ribofuranosyl)imidazole-4-carbonitrile (11) and -carboxamide (12) have been synthesized from the corresponding 5-iodo derivatives 2 and 7 by a palladium-catalyzed cross-coupling reaction with (tri-methylsilyl)acetylene. The aglycons, 5-ethynylimidazole derivatives 14 and 15 were synthesized by the hydrolytic cleavage of the corresponding nucleosides. The antileukemic activity of these nucleosides and base analogues are also described.     

Coupling of 2,6-Dichloropurine and 2,6-Dichlorodeazapurines with Ribose and Ribose Modified Sugars

Abstract

Substituted purine and deazapurine nucleosides are of great interest in medicinal chemistry. Furthermore, 3′-deoxynucleosides exhibit a number of biological activities. In this research the coupling of 2,6-dichloro-1- or 3-deazapurine with protected 3′-deoxyribose is reported. Depending upon coupling conditions and base structure, different anomeric and isomeric mixtures have been obtained. Extensive studies, utilizing chemical and physical methods, have been performed to assign the correct configuration to the resulting nucleosides.     

The Synthesis of 2′-C-Functionalised Nucleosides for Incorporation into Catalytic RNA

Abstract

Five 2′-C-functionalized nucleosides (1–5) have been prepared and incorporated into dinucleoside monophosphates. The effect of the functionality on the stability of the adjacent phosphodiester bond toward hydrolysis by nuclease enzymes and extremes of pH has been assessed.     

Synthesis and Anti-HIV Activity of Different Novel Nonclassical Nucleosides

Abstract

A series of different novel nonclassical nucleosides have been synthesised and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells.     

Synteesis of Certain C-4 Substituted Pyrazolo[3,4-b]-Pyridine Nucleosides Structurally Related to Adenosine and Inosine by Tee Sodiw Salt Glycosylation Procedure

Abstract

Several C-4 substituted pyrazolo[3,4-b]pyridine nucleosides have been synthesized using the sodium salt glycosylation procedure and evaluated for their biological activity.     

New Methods for the Synthesis of Base Sensitive Cyanopyrimidine and Cyanopyridine Nucleosides

Abstract

Four cyanonucleosides, 6, 11, 16 and 21 have been prepared using three synthetic methods that are particularly suited to the preparation of base-sensitive nucleosides.     

The Synthesis of Novel Transition State Analogues Related to Imidazole and Purine Nucleotides Involved in the De novo Biosynthesis of Purines

Abstract

5-Amino-4-sulphonamidoimidazole ribofuranosyl nucleosides and a related imidazothiadiazine dioxide nucleoside have been synthesized as potential inhibitors of enzymes involved in the de novo biosynthesis of purine nucleotides.     

Acyclic Nucleoside and Nucleotide Analogues with Amide Bond

Abstract

A series of acyclic nucleosides and related α-phosphonyl acyclic analogues of dNTP with an amide bond have been prepared. Their antiviral and substrate properties were investigated.     

Nucleosides,XLIV1 Synthesis,Properties and Biological Activity of Indazole Nucleosides

Abstract

Various new haloindazole-1-β-D-ribofuranosides (10-17,20,21) and a 2-β-D-ribofuranoside (18) have been synthesized by the fusion method and by direct halogenations, respectively. The new nucleosides have been characterized by UV and ¹H NMR spectra as well as pK_a determinations. Indazole ribofuranosides behave in aqueous acid like purine and benzimidazole nucleosides showing the same mechanism of cleavage of the glycosidic bonds. Toxicity studies against various cell populations indicate only little biological activities.     

Synthesis of the β-2′,3′-Unsaturated Pentopyranosyl Nucleosides and Their 3′-Hydroxymethyl Congeners

Abstract

Fusion of the glycal 3 and purines/pyrimidines without acid catalyst provides anomeric mixtures of the 2′,3′-unsaturated pentopyranosyl nucleosides 4, which have been worked out to furnish the 3′-hydroxymethyl analogues, e.g. 5.