Constrained Dipeptide Surrogates: 5- and 7-Hydroxy Indolizidin-2-one Amino Acid Synthesis from Iodolactonization of Dehydro-2,8-diamino Azelates.

The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one N -(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆ 4 -unsaturated (2 S ,8 S )-2,8-bis[ N -(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆ 4 -azelate stereoselectively delivered a lactone iodide from which separable (5 S )- and (7 S )-hydroxy indolizidin-2-one N -(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation. X-ray analysis of the (7 S )-hydroxy indolizidin-2-one N -(Boc)amino ester indicated that the backbone dihedral angles embedded in the bicyclic ring system resembled those of the central residues of an ideal type II' β-turn indicating the potential for peptide mimicry.