Preparation of dihydro‐, tetrahydro‐ and hexahydro‐chelidamic‐acid derivatives. Three methods for the preparation of 4‐oxo‐2,6‐piperidine‐dicarboxylic acid (3) and derivatives, required as a synthon for betalaine pigments, were explored. The best method was found to be the catalytic hydrogenation of chclidamic acid (1) with 5% Rh/Alox in water under 2.7 atm. H2 for 33 h at 70° and subsequent esterification with methanol which gave 42% of cis, cis‐4‐hydroxy‐2,6‐piperidine‐ (7) and 10% of 2,6‐cis‐piperidine‐dicarboxylic acid dimethyl ester (8), readily separable by chromatography. Oxidation of 7 with dimethylsulfoxide and a carbodiimide attached to a polymer afforded 90% of 4‐oxo‐2,6‐cis‐piperidine‐dicarboxylic acid dimethyl ester (19). Other methods of oxydizing 7 to 19 were less successful. The electrochemical reduction of 1 followed by esterification with methanol led in a low yield to a mixture of 4‐oxo‐0‐2,6‐trans‐piperidine‐dicarboxylic acid dimethylester (24), its dimethyl acetal 25 and presumably trans‐4‐hydroxy‐r‐2, cis‐6‐piperidine‐dicarboxylic acid dimethyl ester (26). Reaction of 4‐oxo‐hepta‐2E, 5E‐dienoic acid (35) with aqueous ammonia gave a 98% yield of a 3 : 2 mixture of cis‐ and trans‐ammonium‐4‐oxo‐2, 6‐piperidine‐dicarboxylate (39 and 40). The above mentioned catalytic hydrogenation method was also applied to N‐ethyl‐chelidamic acid (16) to give a 4:6 mixture of the N‐ethyl derivatives 17 and 18. Furthermore, a number of functional derivatives of 5, of 19, of 39 and of 40 were prepared. Oxidation of the hydroxy‐diester 7 with dimethylsulfoxide and a carbodiimidc derivative in the presence of trifluoroacetic acid afforded 4‐oxo‐1,2,3,4‐tetrahydro‐2, 6‐pyridine‐dicarboxylic acid dimethyl ester (50). This ester was also obtained under the same conditions from thc keto‐diester 19.
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Hermann et al. (1976) studied this question.