3-Cyclohexenecarboxylic acid, preparation

Cyclohexenyl isocyanate (108), produced from 1-cyclohexenecarboxylic acid (107) and DPPA in situ, reacts with l-(A -pyrrolidinyl)cyclohexene (109) to give the pyridone derivative (110 equation 43). The similar vinyl isocyanate-enamine cyclocondensation presents a general method for the preparation of various pyridone derivatives. 

Taking in consideration that the anti-influenza drug and neuraminidase inhibitor GS-4071 has a cyclohexenecarboxylic acid structure, the cyclohexene phosphonate derivatives 114-123 (Fig. 10) were prepared and tested for TcTS activity.170 Compounds 115 and 117, containing the phosphonate as the monoethyl ester showed only weak inhibition (IC50 values of 4.7 and 5.7 mM, respectively). 

Ammonolysis of alicyclic anhydrides followed by Hofmann degradation is one of the most frequently used methods for the synthesis of alicyclic P-amino acids, since many anhydrides are commercially available cheap substances produced by Diels-Alder addition of maleic anhydride and the corresponding dienes [44], By this method, cis- and frans,-2-aminocyclohexane- and -cyclohexenecarboxylic acids, cis-2-aminocycloheptanecarboxylic acid [45], 3-ewtffo-aminobicyclo [2.2.1 ]heptane-2-ew/o-carboxylic acid, 3-e ifo-aminobicyclo[2.2.1 ]hept-5-ene-2-ertcarboxylic acid and some analogue P-amino acids have been prepared [44, 46-48], For partially unsaturated alicyclic compounds, a modified Hofmann degradation is used, sodium hypochlorite being applied to avoid bromine addition to the double bond [48,49]. 

The preparation of the material starts from of mesityl oxide and ethyl acetoacetate which are cyclized under acidic conditions. The resulting ethyl 4-oxo-2,6,6-trimethyl-2-cyclohexenecarboxylate is subsequently reduced and dehydrated. 

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