Novel functionalized cispentacin derivatives. Synthesis of 1,2,3-triazole-substituted 2-aminocyclopentanecarboxylate stereoisomers

Four 1,2,3-triazole-substituted ethyl 2-amino-3-hydroxycyclopentanecarboxylate diastereomers (3,4-disubstituted cispentacins) with a cyclopentane skeleton were prepared in enantiomerically pure form from racemic β-lactam 7 via enzymatic ring opening, epoxidation and selective ring opening of the oxirane ring with sodium azide. The formation of the 1,2,3-triazole ring system involved click chemistry: 1,3-dipolar cycloaddition of the corresponding 4-substituted azidocarboxylates with diethyl acetylenedicarboxylate.

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Diethyl 1-[(1R,2R,3S,4S)-3-(tert-butoxycarbonylamino)-4-(ethoxycarbonyl)-2-hydroxycyclopentyl]-1H-1,2,3-triazole-4,5-dicarboxylateC21H32N4O9Ee = 98%[α]D24=+64.5 (c 0.66, EtOH)Source of chirality: enzymatic resolution of (±)-6-azabicyclo[3.2.0]hept-3-en-7-oneAbsolute configuration: (1R,2R,3S,4S)

Diethyl 1-[(1R,2R,3S,4R)-3-(tert-butoxycarbonylamino)-4-(ethoxycarbonyl)-2-hydroxycyclopentyl]-1H-1,2,3-triazole-4,5-dicarboxylateC21H32N4O9Ee = 98%[α]D24=+13 (c 0.63, EtOH)Source of chirality: enzymatic resolution of (±)-6-azabicyclo[3.2.0]hept-3-en-7-oneAbsolute configuration: (1R,2R,3S,4R)

Diethyl 1-[(1R,2R,3R,4R)-3-(tert-butoxycarbonylamino)-4-(ethoxycarbonyl)-2-hydroxycyclopentyl]-1H-1,2,3-triazole-4,5-dicarboxylateC21H32N4O9Ee = 98%[α]D24=-18.1 (c 0.6, EtOH)Source of chirality: enzymatic resolution of (±)-6-azabicyclo[3.2.0]hept-3-en-7-oneAbsolute configuration: (1R,2R,3R,4R)

Diethyl 1-[(1R,2R,3R,4S)-3-(tert-butoxycarbonylamino)-4-(ethoxycarbonyl)-2-hydroxycyclopentyl]-1H-1,2,3-triazole-4,5-dicarboxylateC21H32N4O9Ee = 98%[α]D24=+26.2 (c 0.38, EtOH)Source of chirality: enzymatic resolution of (±)-6-azabicyclo[3.2.0]hept-3-en-7-oneAbsolute configuration: (1R,2R,3R,4S)