Carbocyclic analogs of 5'-amino-5'deoxy- and 3'-amino-3'-deoxythymidines

Abstract

The carbocyclic analogue of 5'-amino-5'-deoxythymidine was synthesized from the carbocyclic analogue of 2,5'-O-anhydrothymidine acetate. The carbocyclic analogues of 3'-amino-3'-deoxythymidine and of 1-(3'-amino-2',3'-di-deoxylyxofuranosyl)thymine (an all-cis structure) were synthesized from the carbocyclic analogues of 5'-O-trityl-2,3'-O-anhydrothymidine and 5'-O-trityl-3'-O-(methylsulfonyl)thymidine, respectively. The carbocyclic analogue of 5'-amino-5'-deoxythymidine inhibited cytopathogenic effects (CPE) induced by a TK+ strain of type 1 herpes simplex virus replicating in L929 (mouse connective tissue) cells, but it did not inhibit CPE in Vero cells. In contrast, the all-cis-3'-azido-3'-deoxythymidine analogue demonstrated modest inhibition of CPE in Vero cells, but not in L929 cells.

Azidonucleosides: Synthesis, Reactions, and Biological Properties

“…215,216 The C-2,3′-O-anhydrothymidine derivative 3.325 on treatment with other hand, afforded the expected "up" azidonucleoside 3.328. 217 All these compounds were, however, synthesized as racemic mixtures.…”

“…183 Carbocyclic nucleoside 3.328 showed modest activity against HSV-1 in Vero cells. 217 Compound 3.338 was tested for antiviral activity on HIV (RF strain) infected MT4 cells and showed weak activity. 221 The 5′-triphosphates of 3.349 and 3.352 were evaluated directly as RT inhibitors.…”

“…The C-2,3‘- O -anhydrothymidine derivative 3.325 on treatment with LiN 3 , followed by detritylation, afforded (±)-1-[(1 R ,3 S ,4 S )-3-azido-4-( hydroxymethyl)cyclopentyl]-5-methyl-2,4-(1 H ,3 H )-pyrimidinedione 3.326 . The mesylated derivative 3.327 , on the other hand, afforded the expected “up” azidonucleoside 3.328 . All these compounds were, however, synthesized as racemic mixtures.…”

Synthesis and antiviral activity of the enantiomeric forms of carba-5-iodo-2'-deoxyuridine and carba-(E)-5-(2-bromovinyl)-2'-deoxyuridine

“…ent-10: [a]D20 = -9.6°( c 4.48, MeOH). NMR (DMSO-d6) 1.14-2.79 [overlapping multiplets, 6 H, 2 X CH2, CHCOOU, CHCH2OC(0)Ph], 1.76 [s, 3 H, C(0)CH3], 3.86 [d, J = 6.5 Hz, 2 H, Ctf2OC(0)Ph], 4.48 [m, 1 H, CHOC(0)CH3], 6.57-7.29 (5 H, Ar-H), 11.0 (11) and (-)-(lS,3B,4S)-jV-[3-Acetoxy-4-[(benzoyloxy)methyl]cyclopentyl]urea (ent-11). Refluxing a mixture of 10 or ent-10 (5.9 g, 19.0 mmol), respectively, with diphenyl phosphorazidate (4.2 mL, 19.0 mmol) in 100 mL of benzene under nitrogen for 45 min and cooling to room temperature followed by treatment with gaseous ammonia for 10 min, removal of the solvent, and column chromatography (eluent CHCl3/MeOH, 9/1 v/v) yielded the crude urea derivatives, which were recrystallized from 2-propanol to give 3.6 g (58%) 11 or ent-11, respectively, as colorless crystals.…”

Synthesis and Anti‐HIV Activity of Triazolo‐Fused 3′,5′‐Cyclic Nucleoside Analogues Derived from an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition

“…To study the steric effect for the cycloaddition and to produce other novel compounds, we synthesized the 3'-b-azido compound 6 from 5 following a literature method [12] (Scheme 2). Selective propargylation of the 5'-hydroxy group was achieved under the same conditions as for the preparation of 2 to give precursor 7, which was then cyclized to the triazolo-fused compound 8 and transformed to the 5methylcyctosine compound 9 under the conditions shown in Scheme 2.…”