A short and highly stereoselective route to polyhydroxy-perhydroazaazulenes via a C-(d-galacto-pentopyranos-5-yl)isoxazolidine

A short and efficient route to enantiomerically pure hexahydroxy- and pentahydroxy-perhydroazaazulenes, ring-homologues of castanospermine, starting from the sole isoxazolidine derivative obtained in the 1,3-dipolar cycloaddition of a d-galactose-derived nitrone and methyl acrylate, is established. The procedure allows both backbone and stereochemical modulation of the products by choice of the starting monosaccharide. Structural assignment was based on crystallographic analysis of the starting isoxazolidine and NMR techniques. The products were tested for inhibitory activity against several glycosidases.

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Methyl (2R,3R,5R)-2-benzyl-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)isoxazolidine-5-carboxylateC23H31NO8Ee = 100%[α]D25=-82 (c 0.40, CHCl3)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,3R,5R,1′R,2′R,3′S,4′S,5′R

(3R,5R)-3-Hydroxy-5-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)-2-oxopyrrolidineC15H23NO7Ee = 100%[α]D20=-16 (c 1.0, CHCl3)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 1R,2R,3S,4S,5R,6R,8R

(3R,5R)-1-Benzyl-3-hydroxy-5-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)-2-oxopyrrolidineC22H29NO7Ee = 100%[α]D20=-50 (c 2.7, CHCl3)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 1R,2R,3S,4S,5R,6R,8R

(2R,4R)-4-Hydroxy-2-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)pyrrolidineC15H25NO6Ee = 100%[α]D20=-30 (c 1.0, CHCl3)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,4R,1′R,2′R,3′S,4′S,5′R,6′R,8′R

(2R,4R)-1-Benzyloxycarbonyl-4-hydroxy-2-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)pyrrolidineC23H32NO8Ee = 100%[α]D24=+4.5 (c 3.1, CH2Cl2)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,4R,1′R,2′R,3′S,4′S,5′R,6′R,8′R

(2R,5S,6R,7S,8S,9R,9aR)-2,5,6,7,8,9-Hexahydroxy-perhydroazaazuleneC9H17NO6Ee = 100%[α]D20=+58.9 (c 0.45, MeOH)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,5S,6R,7S,8S,9R,9aR

(2R,6S,7R,8S,9R,9aR)-2,6,7,8,9-Pentahydroxy-perhydroazaazuleneC9H17NO5Ee = 100%[α]D20=+6.1 (c 1.55, MeOH)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,6S,7R,8S,9R,9aR

(2R,4R)-1-Benzyl-4-hydroxy-2-(1,2:3,4-di-O-isopropylidene-α-d-galacto-pentopyranos-5-yl)pyrrolidineC22H32NO6Ee = 100%[α]D20=-29.7 (c 0.3, CH2Cl2)Source of chirality: 1,2:3,4-di-O-isopropylidene-α-d-galactopyranoseAbsolute configuration: 2R,4R,1′R,2′R,3′S,4′S,5′R