Toward the total synthesis of antascomicin B: Building the C10-C16 fragment.

by Rivero-Castro, Juliette; McInstosh, Matthias C.

Antascomicin B is a macrolide isolated from a strain of Micromonospora, It 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 involves an amino Claisen rearrangement to establish the C14, C15 stereocenters. Ring closing metathesis would be an interesting methodol. to install the 1,4-anti stereorelationship. We will describe the progress toward the synthesis of C10-C16 fragment of antascomicin B. Acknowledgement Arkansas Biosciences Institute, National Science Foundation (CHEM-0616154, CHEM-0911638) and NIH (RR-15569).