Total Synthesis of Agelasine F and Synthesis Directed towards ent-Ageloxime D: Two Natural Products with Interesting Biological Activities

Abstract

The work described in this thesis has focused on total synthesis directed towards two different classes of secondary metabolites isolated from the Agelas sponge, ageloxime D and analogs, and agelasine F. Ageloximes were reported to be 7,9 - dialkylpurinium salts carrying a diterpenoid side chain in the 7- position and a hydroxylamine substituent in the 6-position, whereas the agelasines lack the hydroxyl group at N6. There are no reported syntheses of ageloximes, and therefore a synthetic strategy was established. The compounds were tested for biological activity and ent-ageloxime D and geranylgeranyl-ageloxime displayed high activity against the protozoa causing leishmaniasis and Chagas disease in addition to Mycobacterium tuberculosis. Agelasine F was synthesized starting from (S) - carvone, and the synthesis of the side chain focused on avoiding and improving some key steps from the previously reported total synthesis of the enantiomer of agelasine F. This compound has shown interesting activity against some drug resistant strains of M. tuberculosis in vitro and also inhibition of Na, K - ATPase.