Toward the total synthesis of Antascomicin B via amino Claisen and allylic diazene rearrangement sequence

by Rivero, Juliette; McIntosh, Matthias C.

Antascomicin B is a macrolide isolated from a strain of Micromonospora that possesses structural similarities to FK506 and rapamycin and exhibits potent binding ability to FKBP12. Recent reports suggest that small mol. ligands of FKBP12 possess potent neuroprotective and neurodegenerative properties in mouse models of Parkinson's disease. Due to the fact that nature cannot be relied upon as a great source for antascomicin B, synthesis is the only means by which to produce sufficient quantities in order to det. its real medicinal value. Our approach to the C10-16 fragment of antascomicin B involved an amino Claisen rearrangement to establish the C14, C15 stereocenters. A novel acyclic diastereoselective allylic diazene rearrangement that has recently been developed in our lab will be effected to establish 1,4-anti (C11/C14) stereorelationships. We will describe the progress toward the synthesis of C10-C16 fragment of antascomicin B. Acknowledgement Arkansas Biosciences Institute, National Science Foundation (CHEM-0616154) and NIH (RR-15569).