Overview of Synthesis and Applications of Unnatural Lipophilic α-Amino Acids

Abstract

Abstract: Naturally and synthetically obtained lipophilic α-amino acids exhibit diverse properties and applications in academia and industry. Unnatural hydrophobic/lipophilic amino acids lacking polarity in their side chains manifest the biologically significant structure of peptides and proteins. The hydrophobic effect of lipophilic amino acids stabilizes the structure of proteins, peptides, and enzymes during their indigenous folding-unfolding phenomena. The presence of these amino acids in the backbone of protein and peptide-derived drug delivery systems such as lysine-derived surfactants and glycodendrimers can also enhance the cell penetration of drugs of interest. Cationic poly-l-lysine dendrimers, α-amino oleic acid, and a naturally occurring cyclic heptadepsipeptide HUN-7293 are recognized as promising biomaterials for developing prodrugs and also serve as biocompatible surfactants in the food, cosmetic and pharmaceutical industries. The synthesis of unnatural lipophilic amino acids, N-lauroyl sarcosine, N-lauroyl glutamic acid, N-octylglycine, N-myristoyl glycine etc. has gained attention for preparing novel compounds for advanced academic, industrial, and societal applications. This review article discusses the applications and synthesis of hydrophobic/lipophilic α-amino acids using ester enolate Claisen rearrangement, chiral auxiliary, chiral pool, chiral catalysts, and many more relevant methodologies.