Ipobscurines C and D: macrolactam-type indole alkaloids from the seeds of Ipomoea obscura

Separation of the methanolic seed extract of Ipomoea obscura afforded five indole alkaloids, three of them (ipobscurines B-D) being new natural products of a unique structural type characterized as serotonin hydroxycinnamic acid amide-type conjugates with a second phenylpropanoid moiety forming an ether with the 5-OH position of the indole nucleus. Due to an oxidative phenolic coupling between the two phenylpropanoid moieties of the supposed precursor ipobscurine B two 21-membered macrolactams with a phenol ether partial structure are formed: the trans–cis isomers ipobscurines C and D. Their structures were established on the basis of spectral data. Moreover, total synthesis of the racemic erythro- and threo-ipobscurine B 4′,4″-dimethyl ethers and the comparison with the corresponding derivative of natural (−)-ipobscurine B proved an erythro configuration of the latter. Ipobscurines C and D are macrocyclic serotonin-neolignanoid-type lactams; structure elucidation was achieved by spectral data. The acyclic lactam B is a putative precursor; total synthesis of its 4,4′-dimethyl ether and corresponding derivatisation of natural B supported the structure and proved an erythro-configuration.