Cycloisomérisations d'énynes issus de monoterpènes par ...

Abstract :
Abstract
Keywords
Monoterpenes represent a large family of natural molecules, which have a moderate cost and
present interesting olfactive and biological properties. The possibility of obtaining best use
from these natural substrates goes through their functionalization, with the aim at increasing
the known biological activity of such natural products or at investigating novel properties. In
this context, the successful use of selective catalytic tools, respecting the principle of atom
economy, is both interesting and challenging. Catalytic reactions involving carbon monoxide
have already permitted to selectively transform many monoterpene into esters, ketones, or
lactones in the presence of rhodium and palladium complexes. To further ameliorate such
approach and to widen the number of accessible structures, thus developing novel molecules,
we have introduced an intermediate stage consisting in the functionalization of these
substrates: the transformation of the monoterpenic substrate into an enyne, known for its
ability to give rise to cyclocarbonylation and cycloisomerisation reactions.
Several monoterpenes carrying an alcoholic group have been functionalized via an O-
alkynylation reaction to provide the corresponding enynes. Starting from these substrates,
cycloisomerisation reactions catalyzed by complexes of transition metals have been
investigated. Various catalytic systems were used: PtCl2, AuCl3 and [Rh2Cl2(CO)4]. The
Pauson-Khand cyclocarbonylation reaction has also been adressed. Novel bi- and tricyclic
substrates containing cyclopropane, diene or cyclopentenone moieties could be synthetized.
These novel molecules arising from monoterpenes have been isolated and fully characterized
by NMR and mass spectrometry. The study of the various enynes and of the relevant
molecules has shown that the structure of the end products is often dependent on the nature of
the enyne. Furthermore, we have evidenced that rhodium(I) complexes could be involved in
the formation of cyclopropane-fused rings, providing higher selectivities than platinum salts
precursors. Besides, within a collaboration with a research hospital laboratory, the antifungal
biological properties and antiplasmodial activity of these new molecules have been tested:
preliminary results indicate that the generation of a cyclopentenone could result in a
significant increase in the antiplasmodial activity with regard to some monoterpenes.
Keywords :
monoterpenes, enynes, cycloisomerization, cyclocarbonylation, rhodium, platinum, gold
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