1-C-Alkyl imino-d-xylitol and -l-arabinitol derivatives obtained via nucleophilic addition to pentose-derived N-tert-butanesulfinyl imines: sugar- versus chiral auxiliary-induced stereoselectivity

The stereoselective synthesis of 1-C-alkyl iminosugars in the d-xylo and l-arabino series as potential drugs for the treatment of lysosomal diseases has been achieved. The key step involves nucleophilic addition to pentodialdofuranose-derived imines generated using enantiopure tert-butanesulfinamide. Depending on the pentofuranose configuration and structure, the stereoselectivity of this reaction was found to be controlled either by the sugar moiety or by the stereogenic sulfur center.

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Methyl 2,3-di-O-benzyl-5-(SR)-N-tert-butanesulfinylimino-β-l-xylofuranosideC24H31NO5S[α]D25=+42 (c 1.1, CHCl3)Source of chirality: l-xyloseAbsolute configuration: (1S,2S,3R,4S,SR)

Methyl 2,3-di-O-benzyl-5-(SS)-N-tert-butanesulfinylimino-β-l-xylofuranosideC24H31NO5S[α]D25=-38 (c 1.0, CHCl3)Source of chirality: l-xyloseAbsolute configuration: (1S,2S,3R,4S,SS)

Methyl 2,3-di-O-benzyl-5-(SR)-N-tert-butanesulfinylamino-(5R)-5-C-hexyl-β-l-xylofuranosideC30H45NO5S[α]D25=+90 (c 1.1, CHCl3)Source of chirality: l-xyloseAbsolute configuration: (1S,2S,3R,4S,5R,SR)

Methyl 2,3-di-O-benzyl-5-(SS)-N-tert-butanesulfinylamino-(5R)-5-C-hexyl-β-l-xylofuranosideC30H45NO5S[α]D25=-88 (c 0.6, CHCl3)Source of chirality: l-xyloseAbsolute configuration: (1S,2S,3R,4S,5R,SS)

(1R)-1-C-hexyl-1,5-dideoxy-1,5-imino-d-xylitolC11H23NO3[α]D25=-21 (c 1.0, MeOH)Source of chirality: l-xyloseAbsolute configuration: (1R,2S,3S,4R)

Benzyl 2,3-O-isopropylidene-5-(SS)-N-tert-butanesulfinylimino-α-l-lyxofuranosideC19H27NO5S[α]D25=-100 (c 1.2, CHCl3)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1R,2R,3R,4S,SS)

Benzyl (5R)-5-C-butyl-2,3-O-isopropylidene-5-(SS)-N-tert-butanesulfinylamino-α-l-lyxofuranosideC23H37NO5S[α]D25=-21 (c 1.5, CHCl3)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1R,2R,3R,4S,5R,SS)

(1R)-1-C-butyl-1,5-dideoxy-1,5-imino-l-arabinitolC9H19NO3[α]D25=-5 (c 0.6, MeOH)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1R,2S,3S,4S)

Benzyl 2,3-O-isopropylidene-5-(SR)-N-tert-butanesulfinylimino-α-l-lyxofuranosideC19H27NO5S[α]D25=+104 (c 1.0, CHCl3)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1R,2R,3R,4S,SR)

Benzyl (5S)-5-C-butyl-2,3-O-isopropylidene-5-(SR)-N-tert-butanesulfinylamino-α-l-lyxofuranosideC23H37NO5S[α]D25=+26 (c 0.9, CHCl3)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1R,2R,3R,4S,5S,SR)

(1S)-1-C-Butyl-1,5-dideoxy-1,5-imino-l-arabinitolC9H19NO3[α]D25=+3 (c 0.3, MeOH)Source of chirality: d-gulono-γ-lactoneAbsolute configuration: (1S,2S,3S,4S)