American Chemical Society
jo050529k_si_002.cif (22 kB)

Synthesis of Pipecolic Acid-Based Spiro Bicyclic Lactam Scaffolds as β-Turn Mimics

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posted on 2005-07-22, 00:00 authored by Ravindranadh V. Somu, Rodney L. Johnson
A series of 6.5.5 spiro bicyclic lactam scaffolds were synthesized from pipecolic acid in a sequence of reactions that was initiated with the α-allylation of tert-butoxycarbonyl pipecolic acid. Oxidative cleavage of the olefin to give an aldehyde followed by condensation with d-cysteine methyl ester gave a mixture of pipecolyl thiazolidines. Cyclization of the pipecolyl thiazolidines with Mukaiyama's reagent yielded the spiro bicyclic lactams 4ad. Epimerization of the 7‘a bridgehead carbon under acidic conditions was observed for those spiro bicyclic lactam scaffolds with an S stereochemistry at this position. The 6.5.5 spiro bicyclic lactam scaffold with the 3‘S,6‘R,7‘aR stereochemistry mimicked a type II β-turn, while the scaffold with the 3‘S,6‘S,7‘aR stereochemistry mimicked a right-handed poly-d-proline II helix.