Synthesis of tetrazole analogues of amino acids: The Fmoc approach

摘要

The chemistry of heterocycles has acquired immense importance in recent years. Tetrazoles represent an important class of heterocycles which exhibit a wide range of applications in medicinal as well as synthetic chemistry. They are used as cis-peptide bond mimics, drugs in pharmaceuticals and bioisosteres for carboxylic acids [1]. Since the acidity of tetrazole group corresponds closely with that of carboxylic acid, replacement of C-terminal amino acid residue with a tetrazole analogue often preserves or improves the biological activity of parent peptides. Alzheimer's β-secretase (BACE1) inhibitor [2] KMI-420 and its α-isomer are potent drug molecules that possess tetrazole sub-units. They are also employed as catalysts in asymmetric synthesis, peptide chelating agents and metallopeptide stabilizers. Proline-derived tetrazole is a powerful enantioselective catalyst used in conjugate addition reactions, asymmetric aldol, mannich reactions and multicomponent reactions. Tetrazoles exist as 1H and 2H tautomers of which the latter is found to be more stable.^