Degradation of palustrin to (−)‐dihydropalustramic acid ((2R,6S,1′S)‐[6‐(1′‐hydroxypropyl)‐2‐piperidyl]acetic acid), and the structure of palustrin and palustridinThe structure of the macrocyclic alkaloid palustrin is shown to be 1a. Its piperidine unit can be obtained as (−)‐dihydropalustramic acid (6a) by the following sequence of degradation reactions (Scheme 1): catalytic hydrogenation of 1a followed by methylation and Hofmann degradation provides the allyl base 4. the regioselectivity of the Hofmann elimination is explained by intramolecular proton abstraction at C(3) by C(18)‐O−. Catalytic reduction of 4 and subsequent acidic hydrolysis yielded 6a and N, N‐dimethylputrescine (N,N‐dimethyl‐1,4‐butanediamine; 7). Loss of the N‐alkyl group in the formation of 6a occurs during the catalytic hydrogenation step. This interpretation is supported by the results of model experiments. The position of the double bond in 1a is deduced from the IR. spectrum of the bromo‐δ‐lactone 19 prepared by treatment of 1a with N‐bromosuccinimide at pH 4 (Scheme 3). Some of our previously published results on the degradation of dihydropalustrin (2a) are obviously at variance with the newly proposed structure for palustrin (1a). They can easily be explained by assuming a partial hydrogenolysis of the C(17)‐N(1) bond during the preparation of dihydropalustrin from palustrin. Periodate cleavage of dihydropalustramic acid methyl ester (6b) liberates propionaldehyde, which can be trapped by working at pH 7.5 (Scheme 2); at lower pH values it condenses rapidly with the simultaneously generated 3,4,5,6‐tetrahydropyridine derivative 15. The structure of the condensation product is proposed to be 16 on the basis of the isolation of its hydrogenation product, an isomeric dihydropalustramic acid (17).