Plants of the genus Kopsia (Apocyna

Plants of the genus Kopsia (Apocynaceae) have proven
to be fertile sources of novel indole alkaloids, characterized
by unusual carbon skeletons as well as useful biological
activities.1–16 We recently reported the structure
of arboflorine (1), a minor alkaloid isolated from the
stem-bark extract of K. arborea.1 Arboflorine (1) is characterized
by a novel pentacyclic structure, incorporating
a third nitrogen atom embedded within a d-lactam E
ring. We proposed a possible biogenetic pathway from
a preakuammicine-type precursor, featuring an initial
Grob-like fragmentation, conjugate addition by ammonia
to a conjugated iminium ion, a retro-vinylogous
Mannich reaction, followed by an intramolecular Mannich
reaction, en route to the novel ring system of arboflorine
(1). Other recent examples of unusual alkaloids
from Kopsia, which are notable for possessing novel ring
systems, and which were postulated to derive from
known monoterpenoid indole precursors through pathways
involving deep-seated rearrangements and/or loss
of key fragments include, inter alia, mersicarpine,3 and
mersilongine.4 We now report the isolation and structural
elucidation of yet another novel alkaloid, arbophylline
(2), this time from the leaf extract of the same
plant, characterized by an unprecendented heptacyclic
cage structure, and incorporating an acetal unit. Previous
examples of indole alkaloids from Kopsia possessing
a cage structure include the kopsinitarines and
mersingines.12,14