Asymmetric synthesis of 4′-C-benzyl-2′,3′-dideoxynucleoside analogues from 3-benzyl-2-hydroxy-2-cyclopenten-1-one

Both enantiomers of the key intermediate, 2-benzyl-5-oxo-tetrahydro-furan-2-carboxylic acid were obtained by asymmetric oxidation of 3-benzyl-2-hydroxy-2-cyclopenten-1-one with an ee ⩾96%, using the tartaric ester/Ti(OiPr)4/t-BuOOH complex, and transformed to the corresponding 4′-substituted nucleoside analogues with up to 61% overall yield.

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(R)-5-Benzyl-5-hydroxymethyl-dihydro-furan-2(3H)-oneC12H14O3[α]D23=+62.8 (c 3.0, CHCl3)Source of chirality: asymmetric oxidationAbsolute configuration: (R)

1-(5-Benzyl-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dioneC17H20N2O4[α]D23=+23.5 (c 1.0, MeOH)Source of chirality: asymmetric oxidationAbsolute configuration: (2R,5R)

1-(5-Benzyl-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dioneC17H20N2O4[α]D24=+61.6 (c 1.0, MeOH)Source of chirality: asymmetric oxidationAbsolute configuration: (2S,5R)

5-[(6-Amino-9H-purin-9-yl)-2-benzyltetrahydro-furan-2-yl]methanolC17H19N5O2[α]D22=+6.6 (c 4.0, DMSO)Source of chirality: asymmetric oxidationAbsolute configuration: (2R,5S)