syn-Selective dihydroxylation of γ-amino-α,β-unsaturated (Z)-esters from d-serine: stereoselective synthesis of d-iminolyxitol

An efficient and stereoselective synthesis of d-iminolyxitol, a potent α-galactosidase inhibitor, is achieved in 11 steps over 45% overall yield from N-Boc-O-Bn-d-serine. The key step involves the OsO4-catalyzed syn-selective dihydroxylation reaction of the acyclic γ-amino-α,β-unsaturated (Z)-ester controlled by an N-diphenylmethylene group.

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(2S)-3-Benzyloxy-2-(tert-butoxycarbonylamino)propan-1-olC15H23NO4[α]D23=-7.6 (c 0.92, CHCl3)Source of chirality: d-serineAbsolute configuration: (2S)

Methyl (2Z,4S)-5-benzyloxy-4-(tert-butoxycarbonylamino)pent-2-enoateC18H25NO5[α]D23=-4.2 (c 1.43, CHCl3)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (2Z,4S)

Methyl (2Z,4S)-5-benzyloxy-4-(diphenylmethylenemino)pent-2-enoateC26H25NO3[α]D23=-72.8 (c 1.1, CHCl3)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (2Z,4S)

Methyl (2S,3S,4R)-5-benzyloxy-4-(diphenylmethyleneamino)-2,3-isopropylidenedioxypentanoateC29H31NO5[α]D24=-28.0 (c 0.72, CHCl3)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (2S,3S,4R)

(3S,4S,5R)-5-Hydroxymethyl-3,4-isopropylidenedioxypyrrolidin-2-oneC8H13NO4[α]D23=+22.9 (c 0.71, MeOH)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (3S,4S,5R)

(2R,3S,4R)-2-Hydroxymethyl-3,4-isopropylidenedioxypyrrolidineC8H15NO3[α]D25=-48.2 (c 0.12, CHCl3)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (2R,3S,4R)

(2R,3S,4R)-3,4-Dihydroxy-2-hydroxymethylpyrrolidine hydrochlorideC5H12ClNO3[α]D27=+15.4 (c 0.56, H2O)Source of chirality: d-serine, asymmetric synthesisAbsolute configuration: (2R,3S,4R)