Trans-2-Aminocyclohexanecarboxylic acid

Asymmetric Synthesis of trans-2-Aminocyclohexanecarboxylic Acid Derivatives from Pyrrolobenzodiazepine-5,11-diones. 

Reduction of all three of the double bonds in the pyrrolo-benzodiazepine-5,11-dione 105 with excess potassium provides the corresponding trans fused hexahydrobenzene derivative 106 in high yield with complete stereochemical control. The preparation of (+)-perhydro-219A 108 from 106 has been reported 3 and a general method of preparation of derivatives of /ra i-2-aminocyclohexanecarboxylic acid e.g. 107) has recently appeared. 

A. cis- and trans-4-Aminocyclohexanecarboxylic acid. A mixture of 27.4 g. (0.20 mole) of />-aminobenzoic acid (Note 1), 200 ml. of water, and 2 g. of 10% rhodium-0.1% palladium on carbon ciitalyst (Note 2) is placed in a pressure bottle and hydrogenated at 50 p.s.i. When 0.6 mole of hydrogen has been absorbed (Note vl), the mixture is filtered and concentrated under reduced pressure until crystals start to form (Note 4). The mixture is diluted with 200 ml. of dimethylformamide and cooled to 5°, filtered, washed with dimethylformamide, then methanol, and amino-cyclohexanecarboxylic acid, m.p. 292-296° (Note 5). 

ASYMMETRIC SYNTHESIS OF TRANS-2-AMINOCYCLOHEXANECARBOXYLIC ACID DERIVATIVES FROM PYRROLO BENZODIAZEPINE-5,11 -DIONES... 

Alkali metal in ammonia reductions of pyrrolobenzodiazepine-5,11-diones give trans-2-aminocyclohexanecarboxylic acid derivatives (e.g., 4) in enantiomerically pure form.2 3 A method for preparation of cis-2-aminocyclohexanecarboxylic acids related to 4 is based on the enantioselective hydrolysis of symmetrical diesters with pig liver esterase.4 cis-2-Aminocyclohexane derivatives have been used for syntheses of aminocyclitol antibiotics.4 5 6-Alkyl-cis-2-aminocyclohexanecarboxylic acids can be prepared by alkali metal in ammonia reduction of pyrrolobenzodiazepine-5,11-diones followed by olefin hydrogenation the cis-decahydroquinoline alkaloid (+)-pumiliotoxin C has been prepared by this methodology.2... 

Due to the natural occurrence and the novel biological activity, interest in investigations of alicyclic P-amino acids has been aroused. A number of new enantioselective syntheses have been developed and protected by patents [14-26]. The writing of this review was prompted by the renewed interest in the title compound 1. The primary focus was its synthesis and some of its transformations. Besides 1, other alicyclic p-amino acids, such as cis- and trans-2-aminocyclohexanecarboxylic acid (2), 2,3-diendo- and 2,3-c exo-3-aminobicyclo[2.2.1]heptane-2-carboxylic acid (3) and some of their partially unsaturated analogues and derivatives will be mentioned. The biological properties of these and related compounds will also be discussed. 

By means of diastereomeric salt formation, cis- and trans-2-aminocyclohexanecarboxylic acids and 2,3-diendo-3 -aminobicyclo[2.2.1]hept-5-ene-2-carboxylic acid were also separated [79-83],... 

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