A short stereoselective synthesis of the protected uracil 3′-epi-polyoxin C

A short synthetic approach to the protected uracil 3′-epi-polyoxin C 20 has been developed. The stereoselective [3,3]-sigmatropic rearrangement of the corresponding 7-thiocyanato-α-d-xylo-hept-5-enfuranose 6 was employed as the key step to construct the C-5 stereocentre in 5-isothiocyanato-α-d-gluco-hept-6-enfuranose 8 and the formal synthesis of uracil 3′-epi-polyoxin C has been accomplished for the first time. This synthesis provides a facile method for multigram scale preparation and thus is useful for the research into the polyoxins’ structure–activity relationship and to search for more potent and effective anticandidal agents.

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3-O-Benzyl-5,6,7-trideoxy-1,2-O-isopropylidene-5-isothiocyanato-α-d-gluco-hept-6-enfuranoseC18H21NO4S[α]D25=-39.4 (c 0.66, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5R)

5,6,7-Trideoxy-1,2-O-isopropylidene-3-O-triisopropylsilyl-5-isothiocyanato-α-d-gluco-hepto-6-enfuranoseC20H35NO4SSi[α]D25=+47.0 (c 0.55, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3R,4S,5R)

5,6,7-Trideoxy-1,2-O-isopropylidene-5-(methoxycarbonylamino)-α-d-gluco-hept-6-enfuranoseC12H19NO6[α]D25=+147.3 (c 0.28, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

3-O-Benzyl-5,6,7-trideoxy-1,2-O-isopropylidene-5-(methoxycarbonylamino)-α-d-gluco-hept-6-enfuranoseC19H25NO6[α]D25=+44.2 (c 0.33, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

Methyl 3-O-benzyl-5-deoxy-1,2-O-isopropylidene-5-(methoxycarbonylamino)-α-d-gluco-hexofuranuronateC19H25NO8[α]D25=-33.4 (c 0.25, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5S)

Methyl 2′-O-acetyl-3′-O-benzyl-1′,5′-dideoxy-1′-[3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl]-5′-(methoxycarbonylamino)-β-d-gluco-hexofuranuronateC22H25N3O10[α]D25=+22.2 (c 0.16, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5S)