Preliminary studies on the synthesis of rancinamycins from nitrosugars: first total synthesis of (3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-cyclohex-1-enecarbaldehyde

The first total synthesis of (3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-cyclohex-1-enecarbaldehyde from d-glucose is described. The key steps of this synthesis are the stereoselective Michael addition of 2-lithio-1,3-dithiane to 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-α-d-xilo-hex-5-enofuranose followed by the enantioselective two-step transformation of 3-O-benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-6-nitro-β-l-idofuranose into (1S,2S,3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-2-nitro-cyclohexanecarbaldehyde propylene dithioacetal, which was finally converted into the target compound.

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(1S,2S,3S,4S,5S,6R)-5-Benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-2-nitro-cyclohexanecarbaldehyde propylene dithioacetalC20H27NO6S2[α]D20=-60.5 (c 3.75, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1S,2S,3S,4S,5S,6R)

(1S,2S,3R,4S,5S,6R)-5-Benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-2-nitro-cyclohexanecarbaldehyde propylene dithioacetalC20H27NO6S2[α]D20=-43.9 (c 1.94, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1S,2S,3R,4S,5S,6R)

(3S,4S,5S,6R)-5-Benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-cyclohex-1-enecarbaldehydeC17H20O5[α]D20=-29.7 (c 1.63, CHCl3);Source of chirality: d-glucoseAbsolute configuration: (3S,4S,5S,6R)