(-)-Spicigerolide was stereoselectively synthesized from a protected (S)-lactaidehyde. The synthesis of the polyacetylated framework relied on two Zn-mediated stereoselective additions of alkynes to aldehydes as well as a regiocontrolled [3,3]-sigmatropic rearrangement of an allylic acetate. The pyranone moiety was constructed via ring-closing metathesis.

Medical treatments of neuron-related disorders are limited due to the difficulty of targeting brain cells. Major drawbacks are the presence of the blood–brain barrier and the lack of specificity of...