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 molecule ligands of FKBP12 possess potent neuroprotective and neurodegenerative properties in mouse models of Parkinson's disease. Our approach to the C10-21 fragment of antascomicin B involves an asymmetric amino-Claisen rearrangement originally developed by Tsunoda et al.1 We are exploring the scalability of the preparation and rearrangement of an allylic amide possessing a silyloxy group at the terminal position of the alkene.  The Tsunoda-Claisen rearrangement uses inexpensive (S)-a-methylbenzylamine as the chiral auxiliary.  The allylic amide underwent rearrangement to establish the C14 and C15 stereocenters in high yield and good diastereoselectivity. This approach will potentially provide a low cost alternative to the Evans aldol for the preparation of b-siloxy amides formally derived from the aldol reaction of a,�-unsaturated aldehydes.  A surprisingly high yielding acid mediated lactonization was employed to cleave the a-methylbenzyl amide. Details of these studies and further elaboration of the lactone will be discussed. 1. A Total Synthesis of (-)-Antimycin A3b Nishii, T., Yoshizuka, M., Yamasaki, C., Suzuki, T., Ito, S., Tsunoda, T. Tetrahedron Letters, 2000 , 41, 7667-7671.

Toward the total synthesis of Antascomicin B: Building the C10-C21 fragment

243rd National Meeting (2012)

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