Theses Doctoral

Rh(III)-Catalyzed Methodologies Applied to the Synthesis of Unnatural Peptides

Lamartina, Christopher William

Contemporary developments in the field of synthetic peptide methodologies are imperative for enabling the advance of drug design in medicinal chemistry. Although many groundbreaking discoveries have been made in this field in the past few decades, there has only been a recent renaissance in transition metal catalyzed methods which create unnatural amino acids and generate macrocyclic peptide structures. Rh(III)-catalyzed methods which install C-C bonds and C-N bonds across readily available alkene substrates have been an underexplored avenue for peptide modification chemistry.

In this thesis, several novel catalytic methodologies are disclosed which simultaneously install unnatural amino acid motifs during peptide ligation events. In Chapter 3, we report a modular peptide ligation methodology that couples dioxazolones, arylboronic acids, and acrylamides to construct amide bonds in a diastereoselective manner under mild conditions, facilitated by Rh(III) catalysis. In Chapter 4, we disclose a Rh(III)-catalyzed macrocyclization via carboamidation, reacting acryloyl-peptide-dioxazolone precursors and arylboronic acids to form complex cyclic peptides with concomitant incorporation of noncanonical α-amino acids. In Chapter 5, we describe ongoing efforts to develop a complementary Rh(III)-catalyzed hydroamidation reaction which furnishes macrocyclic peptides to expand the chemical space in which complex peptidomimetic molecules can be attained.

Files

  • thumnail for Lamartina_columbia_0054D_18765.pdf Lamartina_columbia_0054D_18765.pdf application/pdf 4.34 MB Download File

More About This Work

Academic Units
Chemistry
Thesis Advisors
Rovis, Tomislav
Degree
Ph.D., Columbia University
Published Here
September 11, 2024