Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation.

Autor:	Twitty JC; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Hong Y; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Garcia B; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Tsang S; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Liao J; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Schultz DM; Department of Process Research & Development, Merck & Co., Inc., MRL, Rahway, New Jersey 07065, United States., Hanisak J; Discovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States., Zultanski SL; Department of Process Research & Development, Merck & Co., Inc., MRL, Rahway, New Jersey 07065, United States., Dion A; Department of Process Research & Development, Merck & Co., Inc., MRL, Rahway, New Jersey 07065, United States., Kalyani D; Discovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States., Watson MP; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2023 Mar 15; Vol. 145 (10), pp. 5684-5695. Date of Electronic Publication: 2023 Feb 28.
DOI:	10.1021/jacs.2c11451
Abstrakt:	A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis of noncanonical amino acids and diversification of peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, and diaminopropanoic acid to aryl alanines and homologated derivatives with varying chain lengths. Attractive features include ability to transverse scales, tolerance of pharma-relevant (hetero)aryls and biorthogonal functional groups, and the applicability beyond monomeric amino acids to short and macrocyclic peptide substrates. The success of this work relied on high-throughput experimentation to identify complementary reaction conditions that proved critical for achieving the coupling of a broad scope of aryl bromides with a range of amino acid and peptide substrates including macrocyclic peptides.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu