1- Aminocyclohexanecarboxylic acid

Isoquinuclidone A 5-g portion of cis- and rra/ij-4-aminocyclohexanecarboxylic acid is mixed with 30 ml of Dowtherm At and heated rapidly to reflux in a flask fitted with a short distilling column. Water distils during the heating, which is continued for about 20 minutes. At this time, the mixture is homogeneous. The cooled solution is... 

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). 

In connection with synthesis of quinomycin model systems, Chen and Olsen found that diethylphosphoryl cyanide is the reagent of choice for coupling amino acid derivatives to cis- or rra/ 5-4-aminocyclohexanecarboxylic acid. Other procedures, including the carbodiimide, p-nitrophenyl active ester, and symmetrical anhydride methods, were less satisfactory. 

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. 

Hydrolysis of reduced quinazoline derivatives has also been performed, as demonstrated by the synthesis of enantiopure 2-aminocyclohexanecarboxylic acid 560 from octahydroquinazoline 559 <2004TA3545>. 

Nohira, H., Watanabe, K. and Kurokawa, M. (1976) Optical resolution of Ar-benzyl-cii-2-aminocyclohexanecarboxylic acid by preferential crystallization, Chem. Lett, 1976, 299-300. 

Alicyclic P-lactams 28 were successfully synthesized via a parallel liquid-phase Ugi four-center three-component reaction, starting from alicyclic P-amino acids such as cis-2-aminocyclohexanecarboxylic acid, c/.s-2-aminocyclopentanecarboxylic acid, 2,3-diexo-3-aminobicyclo-[2.2.1]heptane-2-carboxylic acid and some of their partially unsaturated analogues <02OL1967>. 

A mixture of chlorotrimethylsilane (0.205 mmol) was added to a suspension of n. v-3-aminocyclohexanecarboxylic acid (0.205 mmol) suspended in 500 ml CH2Cl2/acetonitrile, 5 1, and refluxed for 2 hours. Once cooled, triethylamine (0.410 mmol) was added dropwise to the mixture followed immediately by the portionwise addition of triphenylmethyl chloride (0.205 mmol). The mixture was stirred 18 hours and sufficient methyl alcohol was added to dissolve the vessel contents. The solution was concentrated and the residue was partitioned between 800 ml diethyl ether/10% citric acid, 1 1. The ether layer was collected and combined with a 150 ml diethyl ether extraction from the citric acid layer. Combined fractions were extracted three times with 250 ml 2 M NaOH and once with 100 ml water. These layers were washed twice with 150 ml diethyl ether, cooled to 0°C, acidified to pH 7 with 12 M HC1, and re-extracted three times with 200 ml EtOAc. The extract was dried over MgS04, then concentrated, and the product isolated in 85% yield as a white foam. 

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... 

Surprisingly, methods for preparing enantioenriched 3-aminocyclopentanecar-boxylic acids and 3-aminocyclohexanecarboxylic acids have rarely been reported. 

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],... 

The above method was also applicable for enantioselective synthesis of the cis and Cram -aminocyclohexanecarboxylic acid enantiomers [95]. 

Bis(trifluoroacetoxy)iodo]benzene has also been used as a reagent for the Hofmann rearrangement, as illustrated by the conversion of amide 404 into the respective amine 405 (Scheme 3.162) [503], A similar [bis(trifluoroacetoxy)iodo]benzene-induced Hofmann rearrangement has been used for the preparation of both enantiomers of trfl 5 -2-aminocyclohexanecarboxylic acid from fran5-cyclohexane-l,2-dicarboxylic... 

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