Asymmetric synthesis of 2′,3′-dideoxy-3′-fluoroapiofuranosyl nucleosides

An efficient stereoselective synthetic method for each stereoisomer of enantiomerically pure 2′,3′-dideoxy-3′-fluoroapiofuranosyl nucleosides was developed. The key features of this strategy are the enantiospecific fluorination of the tert-alcohol and the orthogonal protection/deprotection of the diol.

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(2R)-2-Hydroxy-2-(benzyloxymethyl)-4-penten-1-yl benzoateC20H22O4[α]D20=+4.0 (c 1.68, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2R

(2S)-2-Fluoro-2-(benzyloxymethyl)-4-penten-1-yl benzoateC20H21FO3[α]D20=+10.6 (c 0.58, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2S

(2R)-2-Fluoro-2-(benzyloxymethyl)-4-penten-1-olC13H17FO2[α]D20=+3.6 (c 0.72, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2R

(2R)-2-Fluoro-2-(hydroxymethyl)-4-penten-1-yl benzoateC13H15FO3[α]D20=-15.7 (c 0.67, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2R

(−)-1-(2,3-Dideoxy-3-fluoroapio-β-l-furanosyl)cytosineC9H12FN3O3[α]D20=-44.4 (c 0.18, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,3S

(+)-1-(2,3-Dideoxy-3-fluoroapio-α-l-furanosyl)cytosineC9H12FN3O3[α]D20=+84.1 (c 0.37, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1R,3S

(+)-1-(2,3-Dideoxy-3-fluoroapio-β-l-furanosyl)thymineC10H13FN2O4[α]D20=+10.0 (c 0.18, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,3S

(+)-1-(2,3-Dideoxy-3-fluoroapio-α-l-furanosyl)thymineC10H13FN2O4[α]D20=+15.4 (c 0.10, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1R,3S

(+)-1-(2,3-Dideoxy-3-fluoroapio-β-d-furanosyl)cytosineC9H12FN3O3[α]D20=+48.7 (c 0.17, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1R,3R

(−)-1-(2,3-Dideoxy-3-fluoroapio-α-d-furanosyl)cytosineC9H12FN3O3[α]D20=-78.0 (c 0.32, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,3R

(−)-1-(2,3-Dideoxy-3-fluoroapio-β-d-furanosyl)thymineC10H13FN2O4[α]D20=-11.8 (c 0.11, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1R,3R

(−)-1-(2,3-Dideoxy-3-fluoroapio-α-d-furanosyl)thymineC10H13FN2O4[α]D20=-14.8 (c 0.11, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,3R