Stimulated by their biological activity, various synthetic
strategies have been developed for this class of compounds.5
In addition, many of these molecules have been used as starting
materials for the synthesis of other complex biologically relevant
natural products.6 Some unnatural analogues have been also
prepared and evaluated for their antitumor activities. In par-
ticular, 7-oxamuricatacin has been reported as a more potent
and selective antitumor compound than muricatacin.7
Stereoselective Rhodium-Catalyzed Conjugate
Addition of Boronic Acids to Unprotected
δ-Hydroxy-γ-butenolides. Synthesis of
(-)-7-Oxamuricatacin and ꢀ-Substituted
Derivatives
Cristina Navarro, Ana Moreno, and Aurelio G. Csa´ky¨*
The search for new analogues with enhanced pharmacological
properties requires the development of new synthetic methods
able to increase the structural complexity in a straightforward
fashion.8Thus,forexample,theavoidanceofprotection-deprotection
steps in the synthetic strategy and the sequential stereoselective
formation of various C-C or C-X bonds in a tandem process
are welcome advantages. The conjugate addition of organome-
tallic reagents to electron-deficient alkenes, one of the main
synthetic methods for C-C bond formation, may constitute a
useful procedure toward these ends.
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica,
UniVersidad Complutense, 28040-Madrid, Spain
ReceiVed October 07, 2008
Among the different types of conjugate additions, the reaction
of aryl- and alkenylboronic acids under RhI catalysis, the
Miyaura reaction,9 has become increasingly popular.10 Com-
pared with other more traditional methods, such as organocu-
prate chemistry, the RhI-catalyzed conjugate addition of orga-
noboronic acids enjoys more environmentally benign conditions,
as the reactions can be carried out in water-containing solvents,
the heavy metal is used in catalytic amounts, and the boron
reagents and side products are of low toxicity, which becomes
especially relevant in large-scale operations. Additionally, many
aryl- and alkenylboronic acids are commercially available or
can be easily prepared by a variety of methods.11 Furthermore,
The chiral δ-hydroxy-γ-butanolide moiety is widely found
among biologically active natural products. We report herein
the stereoselective synthesis of ꢀ-substituted analogues of
these compounds by the RhI-catalyzed conjugate addition
of boronic acids to chiral δ-hydroxy-γ-butenolides, easily
prepared from the chiral pool. The reaction takes place with
high trans diastereoselectivity without protection of the
hydroxyl group. The three-step syntheses of (-)-7-oxamu-
ricatacin (R1 ) H, R2 ) CH2-O-nC10H21) and of new
ꢀ-substituted 7-oxamuricatacin analogues (R1 ) aryl, vinyl)
is reported.
(5) (a) Ferrie, L.; Reymond, S.; Capdevielle, P.; Cossy, J. Synlett 2007, 2891.
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heptadecalactone (muricatacin), isolated from seeds of Annona
muricata,4 an annonaceous acetogenin derivative, shows im-
portant cytotoxic activity on human tumor cell lines.3
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466 J. Org. Chem. 2009, 74, 466–469
10.1021/jo8022395 CCC: $40.75 2009 American Chemical Society
Published on Web 11/18/2008