Totalsynthese von Betalainen

Total Synthesis of Betalaines cis ‐4‐Oxo‐2,6‐piperidinedicarboxylic acid dimethyl ester ( 10 ) was transformed (44%) into the semicarbazone of 2,3‐dihydrobetalamic acid dimethyl ester ( 13/14 ) by a modified Horner ‐ Wittig reagent 12 . Oxidation of 13/14 afforded 41% of a mixture of stereoisomers of betalamic‐acid‐dimethyl‐ester semicarbazone ( 4 ), key intermediate for the synthesis of betalaine pigments. The utility of 4 in this respect was demonstrated on a small scale by its conversion to the dimethyl ester of indicaxanthine ( 9 , 11%) and to the trimethyl ester of betanidine ( 7 , 87%). Hydrolysis of 7 gave betanidine ( 6 ). We further describe the synthesis of the trimethyl ester of an oxidized form of betalamic acid ( 20/21 ) as well as model condensation reactions on the carbonyl group of cyclohexanone, cis ‐4‐oxo‐2,6‐diphenylpiperidine ( 23 ) and its N ‐formyl derivative 27 . Reaction of 4‐oxo‐1,2,3,4‐tetrahydro‐2,6‐pyridinedicarboxylic‐acid dimethyl ester ( 40 ) with acetic anhydride or with triethyloxonium tetrafluoroborate resulted in O ‐acylation or in O ‐alkylation along with dehydrogenative aromatization to yield the derivatives 39 or 42 , respectively, of chelidamic acid.