Total Synthesis of Thailanstatin A

The
total synthesis of the spliceosome inhibitor thailanstatin
A has been achieved in a longest linear sequence of nine steps from
readily available starting materials. A key feature of the developed
synthetic strategy is the implementation of a unique, biomimetic asymmetric
intramolecular oxa-Michael reaction/hydrogenation sequence that allows
diastereo­divergent access to highly functionalized tetrahydropyrans,
which can be used for the synthesis of designed analogues of this
bioactive molecule.