posted on 2014-08-15, 00:00authored byJohn Janetzko, Robert A. Batey
The stereoselective synthesis of
(+)-antimycin A1b has
been accomplished in 12 linear steps and 18% overall yield from (−)-ethyl
lactate. A robust, scalable, and highly diastereoselective montmorillonite
K10-promoted allylation reaction between an α-silyloxy aldehyde
and a substituted potassium allyltrifluoroborate salt provides a general
approach to the core stereochemical triad of the antimycin A family.
The requisite (Z)-substituted potassium allyltrifluoroborate salt
was synthesized using a syn-selective hydroboration/protodeboration
of an alkynylboronate ester, followed by a Matteson homologation reaction.
The total synthesis leverages an MNBA (Shiina’s reagent)-mediated
macrolactonization to generate the 9-membered dilactone ring and a
late-stage PyBOP-mediated amide coupling employing an unprotected
3-formamidosalicylic acid fragment, thereby shortening the longest
linear sequence and, perhaps most notably, generating the antimycin
A C7–C8–C9 stereotriad in a single step using a single
chiral pool-derived stereocenter.