C O M M U N I C A T I O N S
lactone. Being unable to perform the epoxide translocation, we
sought another strategy that would allow us to obtain the natural
product laulimalide from our intermediate 3. It has previously been
shown that the isomerization of allylic alcohols via 1,3-transposition
of a hydroxy group can be catalyzed by a number of high-oxidation-
state oxo complexes of transition metals such as V, W, Mo, and
Re.20 To our delight, the utilization of the Re oxo catalysis
conditions developed by Osborn et al.,21 which involve the highly
active triphenylsilyl perrhenate catalyst O3ReOSiPh3, resulted in
the clean formation of the rearranged product 2 with complete
retention of configuration (Scheme 7). We found that using 1 equiv
of the Re catalyst for 5 min at -50 °C in Et2O was optimal in
obtaining the rearranged allylic product 2 (78% isolated yield),
which was easily separable from the remaining starting material 3
by flash column chromatography on silica gel (97% yield brsm).
Subsequent inversion of the C15 stereogenic center following an
oxidation/CBS-reduction sequence afforded the allylic alcohol
epimeric to 2 at C15. Epoxidation of the latter compound using
Sharpless conditions22 followed by DDQ deprotection ultimately
furnished laulimalide, whose spectral and physical data were in
total agreement with those reported for the natural product.1,23
significant cytotoxic activity. More importantly, this work further
highlights the power of the Ru-catalyzed alkene-alkyne coupling
in the context of macrocyclizations via C-C bond formation.
Acknowledgment. We gratefully acknowledge P. Crews (UC
Santa Cruz) for providing an authentic sample of laulimalide. We
also thank J. Flygare, J.-P. Stephan, and P. Chan at Genentech for
biological testings of our laulimalide analogue. W.M.S. thanks the
National Institutes of Health for a postdoctoral fellowship. We thank
the NIH National Institute of General Medical Sciences (GM 33049)
for their generous support of our programs. We thank Johnson-
Matthey for generous gifts of Pd and Ru salts.
Supporting Information Available: Detailed experimental proce-
dures, full characterization of all products, and NMR spectra. This
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Scheme 7. Completion of the Synthesis of Laulimalide and a
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displayed significant activity against Granta 519 and Jurkat cell
lines with IC50 values of 200 and 182 nM, respectively.
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1
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