Unconventional Fragment Usage Enables a Concise Total Synthesis of (−)-Callyspongiolide

An asymmetric synthesis of (−)-callyspongiolide
is described.
The route builds the macrolide domain atypically from a disaccharide
and a monoterpene without passing through a seco-acid.
Chiral iridium catalysis selectively joins fragments. Subsequent degradation
of an imbedded butyrolactone via perhemiketal fragmentation affords
a stereo- and regio-defined homoallylic alcohol that is engaged directly
in a carbonylative macrolactonization. Further elaboration of the
polyunsaturated appendage provides the natural product in a particularly
direct and flexible manner.