Oxathiolane nucleosides

Mansour et a/. 5 2 have reported the synthesis and the anti-HIV activity of a new class of oxathiolane nucleosides. 2 -dcoxy--3 -oxa-4 -thiacytidine 244 [(-)-dOTC], its enantiomer [(-l-)-dOTC]. and their 5-fluoro analogues... 

As shown in Scheme 12.54, oxathiolane nucleoside 230, has been prepared by the method of Schinazi and Liotta." Thus, the coupling of sUylated flucytosine 231 preparing from 217 with lactol 232 gave racemic compound, 2-hydroxymethyl-5-(5-fluorocytosin-l-yl)-l,3-oxathiolane [( )-FTC], which afforded the title compound 230 after an enantioseiective enzymic resolution and hydrolysis. 

Liotta DC, Schinazi RF, Choi W-B (2002) Intermediates in the synthesis of 1,3-oxathiolane nucleoside enantiomers. US 6346627... 

Figures 6A and B display the IR spectra of forms I and II, respectively, of lamivudine, a 1,3-oxathiolane nucleoside which has anti viral activity ...

Schinazi RF, Lloyd RM Jr, Nguyen M-H, Cannon DL, McMillan A, Ilksoy N, Chu CK, Liotta DC, Bazmi HZ, Mellors JW. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob Agents Chemother 1993 37 875-881. 

Brnalt, J., Kvarnstroem, I., Classon, B., Samuelsson, B. Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-induced Rearrangement of a 2,3-Epoxy Thioacetate. J. Org. Chem. 1996, 61, 3604-3610. 

Stoter R, Clemens IR, Lamont B, Noble SA, Williamson C, Belleau B. The resolution and absolute stereochemistry of che enantiomers of ci s-l(2-f hydroxy methyl )-l.3-oxathiolan-5 yljcytosine (BCH189) Equipotent anti-HIV agents. Nucleosides Nucleotides 1993 12 225-236. 

Jeong LS, Schinazi RF, Beach JW, Kim HO, NampaUi S, Shanmuganathan K, Alves AJ, McMillan A, Chu CK, Mathis R (1993) Asymmetric synthesis and biological evaluation of P-L-(2/J,5.S)- and a-L-(2R,5R)-13-oxathiolane-pyrimidine and -purine nucleosides as poten-tieil anti-HIV agents. J Med Chem 36 181-195... 

Other important members of this class of nucleoside analogues are those that contain an oxathiolane ring system, in particular, the cytosine derivative, BCH-189. This compound showed potent anti-HIV activity. Again it was observed that the five-membered ring system of... 

In the search for an L-sugar that would serve as a chiral template for the synthesis of both the oxathiolane as well as dioxolane nucleosides, L-mannose was consid ed. L-mannose, however, suffers from several disadvantages in that it is not readily available or easily... 

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