Investigations into the Manzamine Alkaloid Biosynthetic Hypothesis

The biomimetic synthesis of a pentacyclic alkaloid (keramaphidin B, 1 ), an intermediate in the biogenetic pathway to the manzamine alkaloids, has been achieved. Compound 1 was formed by an intramolecular Diels–Alder reaction of macrocycle 2 in buffer followed by reduction with NaBH₄. This reaction provides the first direct expeimental evidence for the authors' biosynthetic hypothesis.     

STUDIES DIRECTED TOWARD THE SYNTHESIS OF NAKADOMARIN A

The application of a Pummerer-initiated tandem reaction cascade leads to the highly stereoselective formation of the tetracyclic core of nakadomarin A.     

Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A, and 3,4-dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp.

New manzamine alkaloids, zamamidine C (1), 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2), and 3,4-dihydromanzamine J N-oxide (3), have been isolated from an Okinawan marine sponge Amphimedon species. The structures and stereochemistries of 1-3 were elucidated from the spectroscopic data and chemical derivatization. Zamamidine C (1) is a new manzamine alkaloid possessing a second β-carboline ring via an ethylene unit at N-2 of manzamine D, while 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2) is the first manzamine alkaloid possessing an epoxide ring at C-10 and C-11. Zamamidine C (1) showed significant antitrypanosomal activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and antimalarial activity against Plasmodium falciparum, the causative agent of malaria in vitro.     

Synthetic study on efficient stereoselective construction of tricyclic core skeleton of manzamine A

Tricyclic core skeleton of manzamine A was constructed stereoselectively from the fused nitrogen-containing bicyclic enone 3 via a novel and efficient strategy including sequential stereoselective Diels-Alder reaction, Curtius rearrangement, and intramolecular lactam formation reaction.