Carbocyclic α-amino acids: asymmetric synthesis of all four 1-amino-2-hydroxycyclohexanecarboxylic acids

Bicyclic glutamic acid derivatives

“…It is noteworthy that in contrast to previous work [13][14][15][16] the overall cis/trans diastereoselectivity could not be reversed upon solvent and temperature changes, with the consequence that the above ratio of the four diastereomeric a-amino nitrile esters gained under thermodynamic conditions could not be altered. Thus, even at low temperature in aprotic solvents, the reaction is driven by the thermodynamic stability of the four feasible a-amino nitrile esters.…”

“…At this stage, the different stereoisomers can then be separated by chromatographic methods and the individual compounds are hydrogenolysed to the primary a-amino carboxamides which are finally hydrolysed to the cyclic primary a-amino acids. 16,19 The synthetic strategy applied to the targeted cyclic tris(homoglutamic) acids (i.e., trans-2,3-propanoglutamic acids), starts from racemic 2-carbethoxymethylcyclopentanone 1 prepared from cyclopentanone by a classical Stork enamine procedure. 20 The following imine condensation is run with a slight excess of (S)-1-PEA and (R)-1-PEA, respectively, under azeotropic removal of water in refluxing benzene and leads to a mixture of only the two diastereomeric (E)-imines E-2 and ent-E-2, respectively, in a ratio of 57:43 (Schemes 1 and 2).…”

“…Structures including cyclic isoleucines, bis-and tris-homo-threonines, and homolysines as homochiral cycloaliphatic b-substituted a-quaternary aamino acids with two adjacent chiral centres, have been successfully created by means of the latter protocol. [13][14][15][16] More recently, we have shown that this route is also capable for the synthesis of cyclic trans-tris(homoglutamic) acids. 17 In the course of this investigation we realised that the secondary a-amino a-carbamoyl-g-esters, as their precursors, are also key intermediates for the synthesis of bicyclic glutamate derivatives.…”

Recent progress on the stereoselective synthesis of cyclic quaternary α-amino acids

“…On the other hand, acidic hydrolysis of 98a and subsequent treatment with Dowex resin gave the quaternary α-amino acid (1 S ,2 R )- 100a (Scheme 22). 100…”

Synthesis and Preparative Resolution of the trans‐Cyclohexane Analogues of Phenylalanine

“…Different attempts carried out many years ago to synthesise the racemic target compound by this route were not conclusive with respect to the cis/trans stereochemistry of the amino acid formed, probably due to the precari- ous characterisation techniques employed at that time. [19,20] More recently, synthesis of some enantiomerically pure cisand trans-2-substituted 1-aminocyclohexanecarboxylic acids, constrained analogues of isoleucines [33] and threonines, [34] has been described by means of asymmetric Strecker reactions between 2-substituted cyclohexanones and a chiral amine. To the best of our knowledge, the reaction of 2-phenylcyclohexanone has not been reported.…”