An efficient synthesis of new diastereomeric enantiopure 1-aminocyclopentane-1,2,4-tricarboxylic acids

Novel 1-aminocyclopentane-1,2,4-tricarboxylic acids 11 and 14 containing the glutamic acid skeleton were prepared as two diastereomers characterized by having the carbonyl groups in positions two and four cis to each other and trans with respect to the 1-carboxylic group and as all cis relationship, respectively. The reaction sequences, that is, Diels–Alder reaction to give norbornene cycloadducts, oxidative cleavage of the double bond of the cycloadducts, ensured the proper stereochemistry of both diastereomers. Each diastereomer was prepared in enantiopure form starting from exo- and endo-2-amino-norbornene-2-carboxylic acid derivatives 5 and 6 obtained through a very efficient asymmetric synthesis.

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(−)-8-Phenylmenthyl 2-acetylamino-bicyclo[2.2.1]hept-5-ene-2-carboxylateC26H35NO3mp 188–189 °C (acetone)[α]D25=-49.7 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,2S,4S

(−)-8-Phenylmenthyl 2-acetylamino-bicyclo[2.2.1]hept-5-ene-2-carboxylateC26H35NO3mp 230 °C (acetone)[α]D25=+79.6 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 1R,2S,4R

1-Aminocyclopentane-1,2,4-tricarboxylic acidC8H11NO6[α]D25=+3.1 (c 0.26, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: 1S,2R,4S

3a-Amino-1,3-dioxo-hexahydro-cyclopenta[c]furan-5-carboxylic acidC8H9NO5[α]D25=+6.7 (c 0.25, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: 3aS,5R,6aS