A practical synthesis of (2R)-3,5-di-O-benzoyl-2-fluoro-2-C-methyl-d-ribono-γ-lactone

The title compound was synthesized in 23% overall yield using only one purification in four chemical steps. The key features of this practical synthesis include an asymmetric aldol condensation and an enzymatic hydrolysis to remove the major undesired isomer.

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Ethyl (2R,3R,4R)-4,5-O-isopropylidene-2-fluoro-3-hydroxy-2-methylvalerateC11H19FO5Ee = >99%[α]D25=+16.8 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2R,3R,4R)

Ethyl (2S,3R,4R)-4,5-O-isopropylidene-2-fluoro-3-hydroxy-2-methylvalerateC11H19FO5Ee = >99%[α]D25=+11.0 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2S,3R,4R)

Ethyl (2R,3S,4R)-4,5-O-isopropylidene-2-fluoro-3-hydroxy-2-methylvalerateC11H19FO5Ee = >99%[α]D25=-5.7 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2R,3S,4R)

Ethyl (2R,4R)-4,5-isopropylidene-2-fluoro-3-keto-2-methylvalerateC11H17FO5Ee = >99%[α]D25=+13.4 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2R,4R)

(2R)-3,5-Di-O-benzoyl-2-fluoro-2-C-methyl-d-ribono-γ-lactoneC20H17FO6Ee = >99%[α]D25=+124.6 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2R,3R,4R)

(2S)-3,5-Di-O-benzoyl-2-fluoro-2-C-methyl-d-ribono-γ-lactoneC20H17FO6Ee = >99%[α]D25=+23.6 (c 1.0, CH2Cl2)Source of chirality: 2,3-O-isopropylidene-d-glyceradehyde, asymmetric inductionAbsolute configuration: (2S,3R,4R)