Stereoselective syntheses of polyhydroxylated azepane derivatives from sugar-based epoxyamides. Part 1: synthesis from d-mannose

An approach to the synthesis of polyhydroxyazepane derivatives from sugar-based epoxyamides or epoxyalcohols, in which the total regioselective epoxide opening by nitrogen nucleophiles is the key step, is described. Thus, novel polyhydroxyazepane carboxamides and aminomethyl polyhydroxyazepanes, with potential pharmacological interest, are synthesized from diacetone d-mannose. Configurational assignments of the obtained products were determined.

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N,N-Dimethyl-5,6-anhydro-1-O-benzyl-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC19H25NO6[α]D17=+31 (c 0.52, CH2Cl2)Source of chirality: d-mannose

N,N-Dibenzyl-5,6-anhydro-1-O-benzyl-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC31H33NO6[α]D17=+42 (c 0.82, CH2Cl2)Source of chirality: d-mannose

N,N-Dimethyl-5,6-anhydro-1-O-benzyl-2,3-O-isopropylidene-d-glycero-β-d-manno-heptofuranuronamideC21H29NO6[α]D20=+24 (c 1.40, AcOEt)Source of chirality: d-mannose

N,N-Dimethyl-5,6-anhydro-1-O-benzyl-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC19H25NO6[α]D17=+61 (c 0.94, CH2Cl2)Source of chirality: d-mannose

N,N-Dibenzyl-5,6-anhydro-1-O-benzyl-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC31H33NO6[α]D17=-2 (c 1.68, CH2Cl2)Source of chirality: d-mannose

N,N-Dimethyl-6-azido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC19H26N4O6[α]D17=+101 (c 0.98, CH2Cl2)Source of chirality: d-mannose

N,N-Dibenzyl-6-azido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-d-glycero-α-d-manno-heptofuranuronamideC31H34N4O6[α]D17=-31 (c 0.86, CH2Cl2)Source of chirality: d-mannose

N,N-Dimethyl-6-azido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-d-glycero-β-d-manno-heptofuranuronamideC19H26N4O6[α]D22=-8 (c 0.94, CH2Cl2)Source of chirality: d-mannose

N,N-Dibenzyl-6-azido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-d-glycero-β-d-manno-heptofuranuronamidC31H34N4O6[α]D17=+35 (c 2.2, CH2Cl2)Source of chirality: d-mannose

N,N-Dimethyl-2,7-dideoxy-2,7-imino-5,6-O-isopropylidene-d-glycero-d-manno-heptonamideC12H22N2O5[α]D17=+10 (c 1.05, MeOH)Source of chirality: d-mannose

N,N- Dibenzyl -2,7-dideoxy-2,7-imino-5,6-O-isopropylidene-d-glycero-d-manno-heptonamideC24H30N2O5[α]D17=-25 (c 0.93, MeOH)Source of chirality: d-mannose

N,N-Dimethyl-1,6-dideoxy-1,6-imino-d-glycero-d-manno-heptonamide chlorhydrateC9H19ClN2O5[α]D30=+9 (c 1.2, MeOH)Source of chirality: d-mannose

7-N-Dimethylamino-1,6,7-trideoxy-1,6-imino-d-glycero-d-manno-heptitol dichlorhydrateC9H22Cl2N2O4[α]D17=+19 (c 1, MeOH)Source of chirality: d-mannose

7-N-Dibenzylamino-1,6,7-trideoxy-1,6-imino-d-glycero-d-manno-heptitol dichlorhydrateC21H30Cl2N2O4[α]D20=-3 (c 0.85, MeOH)Source of chirality: d-mannose

N-N-Dibenzyl 1,6,-dideoxy-1,6-imino-d-glycero-d-manno-heptonamide chlorhydrateC21H27ClN2O5[α]D28=-27 (c 1.1, MeOH)Source of chirality: d-mannose