Synthesis of leucascandrolide A via a spontaneous macrolactolization.

We have developed a concise, convergent, and stereocontrolled synthesis of (+/-)-leucascandrolide A (18 steps from commercially available precursors), featuring a complete relay of the initial stereochemical information via a series of diastereoselective transformations. Spontaneous macrolactolization discovered during this synthetic exercise has provided unprecedented access to this macrolide and demonstrated the possibility of accessing even large-ring systems in a highly controlled and efficient manner.