Synthesis of pipecolic acid-based spiro bicyclic lactam scaffolds as β-turn mimics

Ravindranadh V. Somu, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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 4a-d. 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.

Original languageEnglish (US)
Pages (from-to)5954-5963
Number of pages10
JournalJournal of Organic Chemistry
Volume70
Issue number15
DOIs
StatePublished - Jul 22 2005

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