Reverse turn mimetics
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
-D-Glucurono-3,6-lactone and L-cysteine combine in a highly stereoselective manner to give the 7,5-bicyclic thiazolidinlactam 2. The α-hydroxy group of the D-glucurono-3,6-lactone was exchanged for an amino function (to give 13) and, after condensation with L-cysteine methyl ester, the polyol dipeptide 7 was obtained. Peptide couplings proceed without the need to protect the three secondary hydroxy groups of the seven-membered ring. The amino group of 7 was deprotected and selectively elongated to the pseudo-tripeptide 16. The depsipeptide 17 was obtained by condensation of Boc-Ala-OH with the polyol 2. Elongation at the carboxy terminus yielded 19 and 20. The bicyclic scaffold populates a well-defined solution conformation; the hydroxy groups mimic the side chains of hydrophilic amino acids and can be further functionalized.
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