Synthetic studies towards proline amide isosteres, potentially useful molecules for biological investigations

Abstract

2-Ethenylpyrrolidine derivative 8b was prepared from N-protected proline ethyl ester 6b. Bromofluorination of 8b with NBS-Bu 4NF/2HF gave a 1:1 regioisomeric mixture, 9b and 10b (X = Br). Dehydrobromination of 9b and 10b with t-BuOK produced a fluoroolefin 11 and a proline amide isostere model 12, respectively. Deprotection of the Z group in 12 was attempted by treatment with CF 3COOH. Although formation of the useful molecule in pseudopeptide synthesis, 13, was observed as checked by NMR spectra, it seemed to decompose slowly during purification procedure to give a mixture of fluorine-free compounds.