Infractin

Liebigs Annalen der Chemie, 1993, 1993(2).

Synthesis of Manzamine C, Infractine and 6‐Hydroxyinfractine.[Reference: WebLink]

METHODS AND RESULTS:
Manzamine C (1), a β‐carboline alkaloid with antitumor activity isolated from the marine sponge Haliclona sp. was synthesized. The dilithium derivative of 5‐hexynoic acid (6) was alkylated with 7 to give after esterification the methyl 10‐hydroxy‐5‐decynoate (8). The tosylate of 8 was converted into the azide 9 which could be selectively hydrogenated with Lindlar palladium catalyst to give the amino ester 10. Saponification of 10 and acylation with (Boc)2O yielded 11, which was converted with pentafluorophenol into 12. Removal of the Boc group in 12 gave an amino ester as intermediate, which cyclized immediately under high dilution conditions to give the lactam 13 in high yield. Reduction of 13 with LiAlH4 produced the macrocyclic amine 4. The β‐carboline part of 1 was prepared by condensation of N‐benzyltryptamine 14 with the formylacetic acid equivalent 15 to give 16. Dehydrogenation of 16 with Pd‐on‐carbon catalyst led to the orthoester 17, which could be converted into the methyl ester 5 in high overall yield. The 4‐(dimethylamino)pyridine‐catalyzed substitution of the methyl ester function in 5 by the amine 4 gave the amide 29. The analogous reaction of 5 with pyrrolidine or with azacyclotridecane yielded 30 and 31. Reduction of these three amides with LiAlH4 produced 1, 2 and 3.
CONCLUSIONS:
The spectroscopic properties of 1 were identical with those of natural manzamine C. – Condensation of 14 or N‐benzyl‐5‐(benzyloxy)tryptamine (19) with aldehyde 18 yielded the products 20 and 21, which could be dehydrogenated to furnish 22 and 23. From these the methyl esters 24 and 25 with properties identical to those of the known β‐carboline alkaloids Infractine and 6‐hydroxyInfractine could be obtained.