Paloma P. Méndez-Castrillón

Hexose-modified anti-viral analogues of uridine 5′-disphosphate glucose derivatives

Abstract A series of analogues of the anti-viral 5′- O -[[[[(tetrabenzyl-, or tetrabenzoyl-α- d -glucopyranosyl)oxy]-carbonyl]amino]sulfonyl]uridine, in which the α-glucose moiety has been replaced by α-mannose, or galactose, 2-acetamido-2-deoxy-α-glucopyranose, 2-deoxy-α-, and β-glucopyranose, 6-deoxy-α-, and β-glucopyranose and 2,4-dideoxy-α-glucopyranose, has been synthesized by reaction of the corresponding protected hexose having the 1-OH free with chlorosulfonyl isocyanate and 2′,3′- O -isopropylideneuridine. 5′- O -[[[[(2″,3″,4″,6″-Tetra- O -benzoyl-α- d -mannopyranosyl)oxy]carbonyl]- amino]sulfonyl]-2′,3′- O -isopropylideneuridine( 13 ), 5′- O -[[[[(2″,3″,4″,6″-tetra- O -benzoyl- and 2″,3″,4″,6″-tetra- O -benzyl-α- d -galactopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,3′- O -isopropylideneuridine ( 18 and 19 ), 5′- O -[[[[(2″-acetamido-2″-deoxy-3″,4″,6″-tri- O -benzoyl- and 3″,4″,6″-tri- O -benzoyl-2″-deoxy-α- d -glucopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,-3′- O -isopropylideneuridine ( 20 and 21 ) and the deisopropylidenated derivatives of 13 and 21 , showed anti-viral activity similar to that of the corresponding glucose analogues as determined by the inhibition of the cytopathic effect induced by HSV-1 replication.

Synthesis of 2-(β-D-Ribofuranosyl)Thiazole-4-Carboxamide 5′-Phosphate Isosteres

Abstract SUMMARY. The syntheses of 5′-O-sulfamoyl and 5′-O-carbamoyl tiazofurin (9 and 12) are described. One pot reaction of 2′, 3′-O-isopropylidene-tiazofurin (7) with hexabutyldistannoxane and sulfamoyl chloride gave the corresponding 5′-O-sulfamoyl ester, which was deprotected to yield 9. Compound 7 reacted with phenyl chloroformate to give the 5′-O-carbophenoxy derivative which on treatment with ammonium hydroxide followed by deisopropylidenation afforded 12. Improvements on the synthetic route to the starting tiazofurin are also reported.

Uridine-5′-Diphosphate Glucose Analogues. 21. Nucleoside Modified Analogues of Antiviral 5′-O-[[[[(α-D-Glucopyranosyl)Oxy Carbonyl]Amino]Sulfonyl]Uridine Derivatives

Abstract A series of uridine modified analogues of antiviral 5′-O-[[[[(α-D-glucopyranosyl) oxy] carbonyl]amno]sulfonyl]uridine derivatives has been synthesized by reaction of suitably protected glucose and glucosamine derivatives with CISO2-N=C=O and thymidine, 2′-deoxyuridine, 3-methyluridine, 5, 6-dihydrouridine and 1-[(2-hydroxyethoxy) methyl] uracil derivatives. The antiviral activity against HSV-1 has been determined.

Synthesis and Antiviral Activity of 5′-O-Sulfamoyluridine Derivatives

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.

Synthesis and Cytostatic Activity of Halomethylthiazole C-Nucleosides and Analogues1

Abstract The synthesis of 2-(β-D-ribofuranosyl)-and 2-(tetrahydropyran-2-yl)-4-halomethylthiazoles from 2, 5-anhydro-D-allonthioamide and tetrahydropyran-2-thiocarboxamide is described. Bromination of 2-(β-D-ribofuranosyl)- and 2-tetrahydropyran-2-yl)-4-methylthiazole with NBS is studied. Cytostatic activity against HeLa cells of all the compounds is reported.

Mode of action of a new type of UDP-glucose analog against herpesvirus replication.

The mode of action of a new type of UDP-glucose analog against herpes simplex virus type 1 (HSV-1) replication was examined. The analog showed good selectivity and potent activity. At 10 micrograms/ml, P-536 inhibited the formation of infectious HSV-1 by more than 90%, whereas at 100 micrograms/ml it had no cytotoxic effects, as evidenced by phase-contrast microscopy. P-536 showed a wide spectrum of action and was active against HSV-1, adenovirus type 5, vaccinia virus, poliovirus type 1, encephalomyocarditis virus, vesicular stomatitis virus, influenza virus, and measles virus, irrespective of whether these viruses have lipidic envelopes or not. P-536 clearly inhibited protein glycosylation if added at the time when late viral proteins were being synthesized. Moreover, it also interfered with the synthesis of nucleic acids and the phosphorylation of nucleosides. If P-536 was present from the beginning of infection, HSV-1 replication was blocked at an early step and the infected cells continued to synthesize cellular proteins for long periods. Images