Studies on the transformation of nitrosugars into branched chain iminosugars. Part II: Synthesis of (3R,4R,5R,6S)-2,2-bis(hydroxymethyl)azepane-3,4,5,6-tetraol

The first stereocontrolled synthesis of (3R,4R,5R,6S)-2,2-bis-(hydroxymethyl)azepane-3,4,5,6-tetraol is described herein. The method involves a novel double Henry reaction of the 3,5-di-O-benzyl-6-deoxy-1,2-O-isopropylidene-6-nitro-α-d-glucofuranose with formaldehyde followed by a reductive ring closure to give the first branched 1,6-dideoxy-1,6-heptitol described.

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3,5-Di-O-benzyl-6-deoxy-6-C-hydroxymethyl-1,2-O-isopropylidene-6-nitro-α-d-gluco-heptofuranoseC25H31NO9[α]D20=-67.8 (c 1.70, chloroform)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

6-Amino-6-deoxy-6-C-hydroxymethyl-1,2-O-isopropylidene-α-d-gluco-heptofuranoseC11H21NO7[α]D20=-20.3 (c 2.33, methanol)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

(2R,3R,4S,5R,6R)-7,7-Bis-(hydroxymethyl)azepane-2,3,4,5,6-pentaolC8H17NO7[α]D20=-13.9 (c 1.32, methanol)Source of asymmetry: d-glucoseAbsolute configuration: (2R,3R,4S,5R,6R)

(3R,4R,5R,6S)-2,2-Bis-(hydroxymethyl)azepane-3,4,5,6-tetraol hydrochlorideC8H18ClNO6[α]D20=-5.6 (c 1.07, methanol)Source of asymmetry: d-glucoseAbsolute configuration: (3R,4R,5R,6S)