Synthesis and comparative anti-HIV activities of new acetylated 2′,3′-dideoxy-3′-thiacytidine analogues

Retinoic Acid Conjugates as Potential Antitumor Agents: Synthesis and Biological Activity of Conjugates with Ara-A, Ara-C, 3(2H)-Furanone, and Aniline Mustard Moieties

“…Chemistry. The conjugates 3 − 5 , were obtained by reaction of the corresponding nucleosides (Ara-C and Ara-A), protected as 3‘,5‘- O- (1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl) derivatives ( 1 and 2 ), and retinoyl chloride in situ prepared from retinoic acid and oxalyl chloride in benzene (Scheme ) . The reaction gave both N 6 - and 2‘-retinoyl derivatives in the case of Ara-A ( 4 and 5 ) and solely the N 4 -retinoyl derivative in the case of Ara-C ( 3 ).…”

“…Several observations support the design and synthesis of these conjugates: (i) there is evidence of interesting synergistic antitumor effects by simple combination of antiproliferative agents and retinoic acid; − (ii) retinoic acid could be released from its amides and esters by cellular enzymes; , (iii) the retinoic acid prodrug moiety is endowed with differentiating properties as well as with antiproliferative activity; (iv) the increased lipophilicity of a retinoic acid conjugate may improve both the biotransport of the prodrug through cell membranes and the plasma half-life of the conjugated drug. , …”

“…Retinoic acid itself has been reported to inhibit HIV replication. Therefore, it has appeared of interest by different authors to study retinoic acid covalently linked to nucleosides, in order to enhance the uptake of the prodrug by HIV-1-infected cells and to increase its plasma half-life. − …”

ChemoselectiveN-Deacetylation of Protected Nucleosides and Nucleotides Promoted by Schwartz's Reagent

“…O -Acetyl-lamivudine (3h) . Prepared from 2h [ 19a , 25 ] according to standard procedure for the N -deacetylation reaction. The crude compound is purified by flash chromatography on silica gel gradient elution of CH 2 Cl 2 /MeOH from 98/2 to 95/5 to give 3h [ 25 ] as a white solid (0.048 g, 56% yield).…”

“…Prepared from 2h [ 19a , 25 ] according to standard procedure for the N -deacetylation reaction. The crude compound is purified by flash chromatography on silica gel gradient elution of CH 2 Cl 2 /MeOH from 98/2 to 95/5 to give 3h [ 25 ] as a white solid (0.048 g, 56% yield). 1 H NMR (500 MHz) CD 3 OD δ H 1.90 (3H, s, COCH 3 ), 2.95 (1H, dd, J = 3.0, 12.5 Hz, H-4′), 3.35 (1H, dd, J = 5.5, 12.5 Hz, H-4′), 4.20 (1H, dd, J = 3.0, 12.5 Hz, CH 2 OH), 4.35 (1H, dd, J = 5.0, 12.5 Hz, CH 2 OH), 5.20 (1H, dd, J = 3.5, 5.0 Hz, H-2′), 5.70 (1H, d, J = 7.5 Hz, H-5), 6.10 (1H, dd, J = 3.5, 5.5 Hz, H-5′), 7.68 (1H, d, J = 7.5 Hz, H-6); 13 C NMR (125 MHz) CD 3 OD δ C 20.62 (CH 3 ), 38.15 (C-4′), 65.64 (CH 2 OH), 84.44 (C-2′), 89.11 (C-5′), 96.03 (C-6), 142.49 (C-5), 157.83 (C-2), 167.72 (C-4), 172.08 ( C OCH 3 ); MS (ESI+) m/z = 272 [M+1].…”