Herstellung von Dihydro‐, Tetrahydro‐ und Hexahydrochelidamsäure‐Derivaten

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. H 2 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‐2 E , 5 E ‐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 .