Asymmetric syntheses of the methyl 3-deoxy-3-amino-glycosides of d-glycero-l-gulo-heptose, d-glycero-d-galacto-heptose, d-glycero-l-allo-heptose and d-glycero-d-allo-heptose

The methyl glycosides of 3-deoxy-3-amino-d-glycero-l-gulo-heptose, 3-deoxy-3-amino-d-glycero-d-galacto-heptose, 3-deoxy-3-amino-d-glycero-l-allo-heptose and 3-deoxy-3-amino-d-glycero-d-allo-heptose were prepared from the corresponding d-aldopentoses via a seven step synthetic sequence. The doubly diastereoselective conjugate additions of the requisite antipode of lithium N-benzyl-N-(α-methylbenzyl)amide to four diastereoisomeric d-aldopentose-derived α,β-unsaturated esters and in situ enolate oxidation with the requisite antipode of camphorsulfonyloxaziridine (CSO) were used as the key, stereodefining steps. Sequential protection of the C(2)-hydroxyl group within the resultant α-hydroxy-β-amino esters and partial reduction of the ester functionality furnished the corresponding β-amino aldehydes. Subsequent N- and O-deprotection gave the target compounds (as the corresponding methyl pyranosides and/or methyl furanosides) in good yields and high diastereoisomeric purity.

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tert-Butyl (2S,3S,4S,5R,6R,αS)-2-benzyloxy-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanoateC39H51NO7[α]D20 = +0.5 (c 0.8, MeOH)Source of chirality: d-xyloseAbsolute configuration: (2S,3S,4S,5R,6R,αS)

(2S,3R,4S,5R,6R,αS)-1,4,5,6,7-Pentahydroxy-2-benzyloxy-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-di-O-isopropylideneheptaneC35H45NO6[α]D20 = −22.0 (c 1.0, CHCl3)Source of chirality: d-xyloseAbsolute configuration: (2S,3R,4S,5R,6R,αS)

(2S,3S,4S,5R,6R,αS)-2-Benzyloxy-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanalC35H43NO6[α]D20 = −26 (c 0.3, CHCl3)Source of chirality: d-xyloseAbsolute configuration: (2S,3S,4S,5R,6R,αS)

tert-Butyl (2S,3S,4S,5R,6R,αS)-2-(methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanoateC34H49NO8[α]D20 = +38.0 (c 1.5, CHCl3)Source of chirality: d-xyloseAbsolute configuration: (2S,3S,4S,5R,6R,αS)

(2S,3S,4S,5R,6R,αS)-2-(Methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanalC30H41NO7[α]D20 = +9.1 (c 0.7, CHCl3)Source of chirality: d-xyloseAbsolute configuration: (2S,3S,4S,5R,6R,αS)

tert-Butyl (2R,3S,4R,5S,6R,αS)-2-(methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanoateC34H49NO8[α]D20 = +5.9 (c 1.0, CHCl3)Source of chirality: d-arabinoseAbsolute configuration: (2R,3S,4R,5S,6R,αS)

(2R,3S,4R,5S,6R,αS)-2-(Methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-di-O-isopropylidene-4,5,6,7-tetrahydroxyheptanalC30H41NO7[α]D20 = −66.0 (c 0.5, CHCl3)Source of chirality: d-arabinoseAbsolute configuration: (2R,3S,4R,5S,6R,αS)

tert-Butyl (2S,3S,4R,5R,6R,αS)-2-(methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanoateC34H49NO8[α]D20 = −6.6 (c 1.3, CHCl3)Source of chirality: d-lyxoseAbsolute configuration: (2S,3S,4R,5R,6R,αS)

(2S,3S,4R,5R,6R,αS)-2-(Methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanalC30H41NO7[α]D20 = −23.7 (c 0.9, CHCl3)Source of chirality: d-lyxoseAbsolute configuration: (2S,3S,4R,5R,6R,αS)

tert-Butyl (2R,3R,4S,5S,6R,αR)-2-(methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanoateC34H49NO8[α]D20 = +9.3 (c 0.2, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4S,5S,6R,αR)

(2R,3R,4S,5S,6R,αR)-2-(Methoxymethoxy)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5,6,7-tetrahydroxy-4,5,6,7-di-O-isopropylideneheptanalC30H41NO7[α]D20 = −11.0 (c 0.5, CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4S,5S,6R,αR)

Methyl (1R,2R,3S,4S,5R,6R,αR)-3-deoxy-3-[N-benzyl-N-(α-methylbenzyl)amino]-d-glycero-β-d-allo-heptofuranosideC23H31NO6[α]D20 = +0.4 (c 1.0, MeOH)Source of chirality: d-riboseAbsolute configuration: (1R,2R,3S,4S,5R,6R,αR)

(1S,2R,3S,4S,5R,6R,αR)-3-Deoxy-3-[N-benzyl-N-(α-methylbenzyl)amino]-d-glycero-α-d-allo-heptofuranosideC23H31NO6[α]D20 = +96.3 (c 0.8, MeOH)Source of chirality: d-riboseAbsolute configuration: (1S,2R,3S,4S,5R,6R,αR)

Methyl (1R,2R,3S,4S,5R,6R)-3-deoxy-3-amino-d-glycero-β-d-allo-heptofuranosideC8H17NO6[α]D20 = −58.1 (c 1.0, MeOH)Source of chirality: d-riboseAbsolute configuration: (1R,2R,3S,4S,5R,6R)

Methyl (1S,2R,3S,4S,5R,6R)-3-deoxy-3-amino-d-glycero-α-d-allo-heptofuranosideC8H17NO6[α]D20 = +86.1 (c 1.0, MeOH)Source of chirality: d-riboseAbsolute configuration: (1S,2R,3S,4S,5R,6R)