Theoretical Investigation of the Biogenetic Pathway for Formation of Antibacterial Indole Alkaloids fromVoacanga africana

Abstract

The energetic viability of the previously proposed biogenetic pathway for the formation of two unique monoterpenoid indole alkaloids, voacafricine A and B, which are present in the fruits of Voacanga africana , was investigated using density functional theory computations. The results of these calculations indicate that not only is the previously suggested pathway not energetically viable but also that an alternative biosynthetic precursor is likely.

Divergent Asymmetric Total Synthesis of (−)‐Voacafricines A and B

“…19‐ epi ‐Voacristine, an iboga‐type indole alkaloid co‐isolated from the same tree, was suggested to be a plausible biogenetic precursor. However, the energy barriers for the proposed skeleton reorganization steps were found to be too high to be kinetically feasible on the basis of recent DFT calculations [2] …”

“…However, the energy barriers for the proposed skeleton reorganization steps were found to be too high to be kinetically feasible on the basis of recent DFT calculations. [2] Structurally, voacafricines A (1) and B (2) are hexacyclic compounds containing an unprecedented 8alkyl octahydro-2H-5,8-methanofuro [2,3-b]azepin-8-ium motif with five contiguous stereocenters. Different from other alkaloids bearing a bridged bicyclic ammonium moiety, such as taberdivamines A, B, [3] excelsinidine, [4] nor-excelsinidine [5] and subincanadines A and C (Figure 1), [6] one of the quaternary N + À C bonds in voacafricines A (1) and B ( 2) is part of an aminal functionality.…”