Zhan B.-B,
Fan J,
Jin L,
Shi B.-F.
* Zhejiang University, Hangzhou, P. R. of China
Divergent Synthesis of Silicon-Containing Peptides via Pd-Catalyzed Post-Assembly
γ-C(sp
3)–H Silylation.
ACS Catal. 2019;
9: 3298-3303
Key words
late-stage functionalization - peptide modification - silylation - palladium catalysis
- C–H activation
Significance
Chemically modified unnatural peptides are often endowed with improved biological
and pharmacokinetic properties and are therefore valuable in the drug-discovery process.
Modification by silicon-containing groups appears to be promising, because the presence
of a silicon moiety in amino acids or peptides can help to improve permeation through
membranes and increase proteolytic stability.
Comment
Shi and co-workers have developed an efficient procedure for the synthesis of various
γ-silyl-α-amino acids and oligopeptides by palladium(II)-catalyzed γ-C(sp3)–H silylation. The present site-specific late-stage C(sp3)–H functionalization is assisted by a picolinamide auxiliary and uses cheap and commercially
available hexamethyldisilane as a silylating agent. Compatibility with a broad range
of amino acid residues and the facile removal of the picolinamide auxiliary are noteworthy
features of the present protocol.
