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very high diastereoselectivity (.98 : 2) in favour of the desired anti,
syn adduct. Using the enantiomeric (S)-mesyl-butynol, the
diastereomeric adduct (19, Scheme 5) was prepared (84% yield)
with a 95 : 5 anti, anti : anti, syn ratio, which could be used to
access 12,13-epi-dictyostatin,{ a compound for which structure–
activity relationships are still completely lacking.4d Finally, TBS
protection of alcohol 18 afforded the desired fragment 2 (Scheme 4)
ready for further elongation of the carbon chain.
In conclusion, we have synthesised the C10–C23 fragment of
(2)-dictyostatin using a highly convergent and stereocontrolled
route. Besides targeting the natural product, this route can be used
to access a number of analogues (e.g. 12,13-epi-dictyostatin) and
gain a better understanding of the structure–activity relationships
of this class of molecules.
We thank the European Commission for financial support and
for a postdoctoral fellowship to O. Sharon (‘‘Marie Curie’’ MEIF-
CT-2003-500880). We also gratefully acknowledge Merck
Research Laboratories (Merck’s Academic Development
Program Award to C. Gennari) and Ministero dell’Universita` e
della Ricerca (PRIN prot. 2006030449) for financial support and
for a postdoctoral fellowship (Assegno di ricerca) to C. Monti.
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Notes and references
{ For more details on the addition of either (R)-mesyl-butynol or
(S)-mesyl-butynol, see the ESI{.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 4271–4273 | 4273