Asymmetric Synthesis of alpha-Methyl alpha-Amino Acids by Diastereoselective Alkylation of Optically Active 6-Isopropyl-3-methyl-2,3-dihydro-6H-l,4-oxazin-2-ones

摘要

The present, high interest in the synthesis of nonproteino-genic amino acids is based on their remarkable pharmacological and confbrmational properties, both as free amino acids and as components of biologically active peptides. alpha-Methyl alpha-amino acids (AMAA) are important members in the family of modified amino acids. Some representative examples are a) naturally occurring alpha-aminoisobutyric acid (Aib) and (R)-2-amino-2-methylbutyric acid (D-Iva), which are constituents of peptaibols (microbial peptide antibiotics that form transmembrane ion channels), b) (S)-alpha-methyl-DOPA (Aldomet), which is an inhibitor of DOPA decarboxylase (an important commercial anti-hypertensive) ; c) (S)-alpha-methyltyrosine, which (as a substitute of tyrosine4 in angiotensin II) results in a peptide that is resistant to chymotryptic degradation, and d) (R)-a-methylaspar-tic acid, (R)- or (S)-2-methylglutamic acids, as well as (R)-and (S)-alpha-methylserine, which can be used to stabilize beta-turn and alpha-helical conformations in short peptides.