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ID: ALA1145730

Journal: Bioorg Med Chem Lett

Title: Nodulisporic acid side-chain modifications: access to the 2", 3", 4", and 6" registers.

Authors: Chakravarty PK, Shih TL, Colletti SL, Ayer MB, Snedden C, Kuo H, Tyagarajan S, Gregory L, Zakson-Aiken M, Shoop WL, Schmatz DM, Wyvratt M, Fisher MH, Meinke PT.

Abstract: Efficient routes to access the 2", 3", 4", and 6" registers of the nodulisporic acid (NsA) side chain are disclosed. A mild one-carbon, Ph(2)CdoublebondNCH(2)CtriplebondN mediated homologation of NsA's 3"-aldehyde permitted access to the 4"-register. Curtius reaction of NsA's 3"-acid yielded the corresponding 2"-aldehyde 4 from which the unnatural Delta(2",3")-olefin isomer 2b was obtained. In addition, Arndt-Eistert reactions of the parent NsA permitted a one-carbon homologation to the 6" register. These efforts identified new analogues with significant flea activity and illustrated the biological significance of unsaturation at the 1",2" register.

CiteXplore: 12467636

DOI: 10.1016/s0960-894x(02)00826-0