10.1016/S0040-4020(00)01008-5
The research focuses on the synthesis of spiroazabicycloalkane amino acid scaffolds, which serve as reverse-turn inducer dipeptide mimics. These conformationally constrained molecules are designed to mimic Ala-Pro dipeptide units or more generally, the central (i+1 and i+2) residues of β-turns in peptide chains. The methodology involves a series of chemical reactions starting from known compounds, utilizing reagents such as LiEt3BH, Ac2O, allyltributyl tin, BF3.Et2O, OsCl3, and NaBH4, among others, to produce the desired scaffolds. The experiments include hydrogenolysis, hydrolysis, protection of nitrogen atoms, dihydroxylation, oxidation, and olefination steps. The analyses used to characterize the intermediates and final products encompass 'H and 13C NMR spectroscopy, elemental analysis, mass spectrometry, and optical rotation measurements. Single crystal diffraction analysis was also performed to secure the configuration of the diastereoisomeric alcohols. The study successfully demonstrates a practical approach to synthesize these constrained scaffolds, which could potentially improve peptide-receptor affinity by interacting with hydrophobic pockets, thereby enhancing the metabolic stability of peptides.
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