Silicon-Containing Amino Acids: Synthetic Aspects, Conformational Studies, and Applications to Bioactive Peptides

Abstract

Unnatural α-amino acids form a family of essential molecules used for, among other applications, the synthesis of modified peptides, to improve resistance to proteolytic enzyme degradation, and to modulate physico- and biochemical properties of bioactive peptides as well as chiral inducers in asymmetric synthesis. Among them, silicon-containing unnatural amino acids are becoming an interesting new class of building blocks. The replacement of carbon atoms in bioactive substances with silicon is becoming increasingly popular. Peptides containing silyl amino acids hold great promise for maintaining or reinforcing the biological activity of active compounds, while they simultaneously enhance their resistance to enzyme degradation. In addition, the lipophilicity of the silicon atom facilitates their membrane crossing and their bioavailability. Nowadays, the interest of the pharmaceutical industry in peptide- and protein-based therapies is increasing. In this respect, silicon-containing amino acids and peptides are likely to be a significant part of future innovations in this area, and more generally in the area of biomolecules. In this process, commercial availability of silicon-containing amino acids is necessary: new syntheses have been developed, and work in this area is ongoing. This review aims to be a comprehensive and general summary of the different methods used to prepare silicon-containing amino acids and their implications on conformational structures and biological applications when they are incorporated into bioactive molecules.

Silicon amino acids

“…In particular, their importance have been remarked and industrialized since the late 20th century, which was connected with the rise of genetic technologies and proteomics. It is notable that Mortensen et al in 2009, as well as Rémond et al in 2016 stated that the major future goals of silicon‐containing amino acids chemistry are the synthesis of another molecules and further diversity in their side chains . According to this suggestion, we decided to investigate the possible stability of novel silicon amino acids (SiAA) in which all carbon atoms (including the carbon atom in the carboxylic COOH group) are replaced by the silicon atoms.…”

Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles

“…30 This instability is attributable to lengthening and weakening of the Si–C bond caused by the adjacent electron-withdrawing groups. However, 51 and 55 exhibited an incompatibility with silica gel and alumina, which can be explained by this relationship between α -substituted α -silyl amines and the electronic characteristics of the α substituent.…”

Recent Progress in the Transition‐Metal‐Catalyzed Activation of Si−Si Bonds To Form C−Si Bonds

“…Introducing silyl groups into amino acids is attractive, because silicon can strongly affect the stability,s olubility,l ipophilicity, and pharmacokinetic properties of the resulting peptidesa nd proteins. [41] Most studies have focused on the diastereoselective synthesis of b-silyl-a-amino acids, [42] which are traditionally synthesized in multistep pathways involving expensive chiral auxiliaries. Shi and co-workerss tart from corresponding aamino amides 108 containing 8-aminoquinoline as ar emovable directing group to achieve C(sp 3 )ÀHs ilylation selectively at the b position( Scheme 27); [43] no competitive C(sp 2 )ÀHs ilyla-Scheme26.…”