Synthesis of aldopentapyranose-derived nitrones by silylation or Cu(II)-catalyzed aerobic oxidation of N-glycosylhydroxylamines

A series of new enantiomerically pure nitrones derived from 3,4-O-isopropylidene l-erythrofuranose, per-O-benzylated l-arabino-, d-xylo-, and d-ribopyranose were synthesized. Whereas silylation of the starting N-glycosylhydroxylamines provided open-chain nitrones functionalized with terminal hydroxyl group protected as silyl ether, the Cu(II)/base-catalyzed aerobic oxidation yielded benzaldehyde-derived nitrones decorated at the N atom with a pyranosyl carbohydrate auxiliary.

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N-Benzyl-1-(hydroxyimino)-2,3,4-tri-O-benzyl-l-arabinopyranose, mixture of tautomersC33H35NO5Ee = mixture of anomers and the open-chain tautomer in 9:2:1 ratio[α]D22 = +12.0 (c 0.53, CHCl3)Source of chirality: l-arabinoseAbsolute configuration: (2R,3S,4S)

N-Benzyl-1-(hydroxyimino)-2,3,4-tri-O-benzyl-d-ribopyranose, mixture of tautomersC33H35NO5Ee = mixture of single anomer and the open-chain tautomers in 2:1 ratio; E/Z ratio of nitrone tautomer in 1:10[α]D22 = +14.7 (c 0.59, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4R)

(Z)-N-Benzyl-(2,3-O-isopropylidene-4-O-tert-butyldiphenylsilyl)-l-erthrosylideneamine N-oxideC30H37NO4SiEe = 100%[α]D22 = −8.3 (c 0.69, CHCl3)Source of chirality: chiral substrateAbsolute configuration: (2R,3S)

(Z)-N-Benzyl-(2,3,4-tri-O-benzyl-5-O-tert-butyldiphenylsilyl)-l-arabinosylideneamine N-oxideC49H53NO5SiEe = 100%[α]D22 = +3.1 (c 1.20, CHCl3)Source of chirality: chiral substrateAbsolute configuration: (2S,3R,4S)

(Z)-N-Benzyl-(2,3,4-tri-O-benzyl-5-O-tert-butyldiphenylsilyl)-d-xylosylideneamine N-oxideC49H53NO5SiEe = 100%[α]D22 = −75.3 (c 0.69, CHCl3)Source of chirality: chiral substrateAbsolute configuration: (2S,3R,4R)

(Z)-N-Benzyl-(2,3,4-tri-O-benzyl-5-O-tert-butyldiphenylsilyl)-d-ribosylideneamine N-oxideC49H53NO5SiEe = 100%[α]D22 = +17.3 (c 1.28, CHCl3)Source of chirality: chiral substrateAbsolute configuration: (2S,3S,4R)

(Z)-N-Benzylidene-2,3,4-tri-O-benzyl-β-l-arabinopyranosylamine N-oxideC33H33NO5Ee = 100%[α]D22 = −6.6 (c 0.57, CHCl3)Source of chirality: asymmetric oxidationAbsolute configuration: (1S,2R,3S,4S)

(Z)-N-Benzylidene-2,3,4-tri-O-benzyl-β-d-xylopyranosylamine N-oxideC33H33NO5Ee = 100%[α]D22 = −15.7 (c 0.57, CHCl3)Source of chirality: asymmetric oxidationAbsolute configuration: (1R,2R,3S,4R)

(Z)-N-Benzylidene-2,3,4-tri-O-benzyl-β-d-ribopyranosylamine N-oxideC33H33NO5Ee = 100%[α]D22 = +68.8 (c 0.70, CHCl3)Source of chirality: asymmetric oxidationAbsolute configuration: (1R,2R,3R,4R)