Practical syntheses of optically active carbagalactose and their potential application to the carbocyclic analogues of KRN7000

Carba-α- and β-d-galactose derivatives were efficiently prepared from a cyclohex-3-ene-1,2-diol derivative 1. Regioselective inversion of 2-OH, and stereoselective dihydroxylation of 1 were accomplished to provide a carba-β-d-galactose derivative 6 in a good yield and with a high stereoselectivity. Stereo-inversion of 1-OH of 6 via oxidation/reduction gave carba-α-d-galactose derivative 12 with a high stereoselectivity. An efficient coupling of carba-α-galactose 12 with an aziridine derivative of sphingosine has been demonstrated to give 1-O-carba-α-galactosyl sphingosine derivative 14.

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(1R,2R,5S)-5-(tert-Butyl-diphenylsilanyloxymethyl)-2-p-nitrobenzoyloxy-cyclohex-3-ene-1-olC30H33NO6Si[α]D27=-131.5 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,5S)

(1R,2R,5S)-5-(tert-Butyl-diphenylsilanyloxymethyl)-1-methoxymethoxy-2-benzyloxy-cyclohex-3-eneC32H40O4Si[α]D26=-92.2 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1R,2R,5S)

Methoxymethyl 2-O-benzyl-6-O-(tert-butyl-diphenyl)silyl-5a-carba-β-d-galactopyranosideC32H42O6Si[α]D27=+29.2 (c 1.0, CHCl3)Source of chirality: enzymatic resolution

Methoxymethyl 2-O-benzyl-6-O-(tert-butyl-diphenyl)silyl-5a-carba-β-d-allopyranosideC32H42O6Si[α]D27=+0.6 (c 1.0, CHCl3)Source of chirality: enzymatic resolution

2,3,4,6-Tetra-O-benzyl-5a-carba-β-d-galactopyranoseC35H38O5[α]D27=-12.6 (c 1.0, CHCl3)Source of chirality: enzymatic resolution

(2R,3S,4S,5R)-2,3,4-Tri-bezyloxy-5-benzyloxymethyl-cyclohexanoneC35H36O5[α]D27=+10.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (2R,3S,4S,5R)

2,3,4,6-Tetra-O-benzyl-5a-carba-α-d-galactopyranoseC35H38O5[α]D25=+20.8 (c 1.0, CHCl3)Source of chirality: enzymatic resolution

(2S,3R,4E)-3-Benzyloxy-1-(2′,3′,4′,6′-tetra-O-benzyl-5a-carba-α-d-galactopyranosyloxy)-2-(p-toluenesulfonylamino)-4-octadeceneC67H85NO8S[α]D25=+13.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (2S,3R,4E)