title: Flexible synthetic routes to poison-frog alkaloids of the 5,8-disubstituted indolizidine-class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F.
abstract: BACKGROUND
  The 5,8-disubstituted indolizidines are the largest class of poison-frog alkaloids found in anuran skin, and are of considerable interest because of their inhibitory effects on the neuronal nicotinic acetylcholine receptors. Many synthetic strategies for the construction of this nucleus have been reported: however, a flexible route has not been reported to date.
  
  
  RESULTS
  Synthesis of lactam chiral building blocks for the flexible synthesis of the title alkaloids has been achieved using a Michael-type conjugate addition reaction to a chiral cyclic enamine ester as the key step in constructing the trisubstituted piperidine ring system. To demonstrate the usefulness of these chiral building blocks, syntheses of (-)-203A, (-)-205A from 1, and (-)-219F from 2 have been achieved.
  
  
  CONCLUSIONS
  The total synthesis of (-)-203A, (-)-205A, and (-)-219F was achieved, and the absolute stereochemistry of natural 203A was determined to be 5S, 8R, 9S. In addition, the relative stereochemistry of natural 219F was determined.
authors: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan. toyooka@pha.u-toyama.ac.jp
authors: Naoki
authors: N
authors: Toyooka
authors: Dejun
authors: D
authors: Zhou
authors: Hideo
authors: H
authors: Nemoto
authors: H Martin
authors: HM
authors: Garraffo
authors: Thomas F
authors: TF
authors: Spande
authors: John W
authors: JW
authors: Daly