ORGANIC
LETTERS
2006
Vol. 8, No. 22
5137-5140
A Concise Total Synthesis of the Lichen
Macrolide (+)-Aspicilin
Christophe Dubost,‡ Istva´n E. Marko´,*,‡ and Thomas Ryckmans†
UniVersite´ Catholique de LouVain, De´partement de Chimie, 1 Place Louis Pasteur,
B-1348 LouVain La NeuVe, Belgium and Pfizer Global Research and DeVelopment,
Sandwich, Kent CT13 9NJ, England
Received August 17, 2006
ABSTRACT
The total synthesis of the polyhydroxylated macrolide (
aldehyde 6 with the uniquely functionalized allylstannane 1. (
+
)-aspicilin 5 is described using as a key step a highly diastereoselective allylation of
)-Aspicilin is obtained in 18 steps and 10% overall yield.
+
We have previously shown1 that enantiomerically pure syn-
anti and syn-syn configured triol units such as 3 and 4 could
be synthesized efficiently by the SnCl4-mediated allylation
of chiral R-benzyloxyaldehydes 2 with the uniquely func-
tionalized allylstannane 1. Remarkably, the relative stereo-
amount of Lewis acid employed (Scheme 1). The resulting
structures possess a stereodefined polyoxygenated triad
present in a large number of natural products. (+)-Aspicilin,
an 18-membered macrolide first isolated from Lecanoraceae
lichen in 1900 by Hesse,2 embodies a contiguous syn-anti
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2004, 60, 7693.
Scheme 1
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chemistry of these adducts was governed solely by the
† Pfizer Global Research and Development.
‡ Universite´ Catholique de Louvain.
10.1021/ol0620287 CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/30/2006