Silicon-Containing Amino Acids and Peptides. Asymmetric Synthesis of (Trialkylsilyl)alanines

摘要

Synthetic amino acids which bear unnatural side chains have proven useful for probing the structural requirements for the activity of numerous peptides and proteins and for imparting novel properties, such as metal-complexing abilities, to peptides. Trialkylsilyl groups are known for having nonpolar, hydrophobic properties relevant to biological activity, so we became interested in developing means for imparting such properties into peptides by the use of (trialkysilyl)alanines. Peptides containing such residues in place of naturally occuring residues might exhibit enhanced biological activities, tissue absorbance properties, and proteolytic stabilities due to the hydrophobicity and large volume (relative to the corresponding hydrocarbon groups) ofthe trialkylsilyl side chains. Moreover, by using the rich substitution chemistry known for organosilanes, one might be able to develop silicon-functionalized trialkyl-silyl-containing amino acids for the placement of silicon-bearing functionality into peptides including, conceivably, disiloxane crosslinks and silicone--peptide co-polymers, with potential applications to peptide dnig design and the development of biocompatible polymeric materials.