FWF - J 3466-N28 - Natural Product Synthesis of (+)-Brefeldin A

Project: Research project

Project Details


In this project an asymmetric synthesis of potential anti-cancer natural product (+)-Brefeldin will be attempted.

The asymmetric total synthesis of (+)-Brefeldin A, a potent anticancer agent, which has in addition several
other pharmaceutically interesting activities, is outlined and proposed inhere. Within the project a new synthetic
strategy is presented involving ring closing alkyne metathesis, a recently developed trans-hydrogenation as well as
an elegant and simple route for the synthesis of the required alkyne from the corresponding lactone. As
pharmaceutical interest in the title compound has risen due to the exquisite pharmaceutical properties of (+)-
Brefeldin A, the new developed synthesis does not only aim on a short and convenient route, but also aims for high
quantities of the natural product to supply medicinal studies with sufficient amounts for further testing. Therefore
several routes towards the cyclopentanol core of the molecule are proposed and will be evaluated during the project
with regard to their feasibility to meet the requirements outlined in the proposal below [e.g. high yields in
combination with highly practicable protocols at a large batch size (multigram scale)]. These routes include
biocatalytic methods, which are based on enzymatic resolution in order to install the required asymmetry at an
early-stage precursor. The total synthesis is completed via ring closing alkyne metathesis (RCAM) forming the
macrocylce and subsequent catalytic trans-hydrogenation to give (+)-Brefeldin A.
Effective start/end date1/10/1330/09/15