Pd-Catalyzed Picolinamide-Directed Late-Stage Chalcogenation of Tryptophan-Containing Peptides

Abstract

This report describes the Pd-catalyzed late-stage chalcogenation of tryptophan-containing peptides with disulfides/diselenides in moderate to good yields. It comprises broad substrate scope, functional group diversity, late-stage modification of drug molecules, and various valuable synthetic transformations, including room temperature easy removal of the picolinamide auxiliary, which could be applicable to tune the structure and function of peptides.

Pd-Catalyzed Picolinamide-Directed C(sp2)–H Sulfonylation of Amino Acids/Peptides with Sodium Sulfinates

“…All required materials were purchased from commercial suppliers and used without further purification. The compounds 1a–g , , 1h , 1j , 1w–z , , 1ac , 1al – am , 2c , and 2e–i , were synthesized by following the literature reported procedure. All the heating reactions were carried out over a magnetic stirrer with a hot plate using heating blocks.…”

“…Over the past decade, the transition-metal-catalyzed direct functionalization of C–H bonds has emerged as an attractive, atom and step-economic alternative for the development of C–S bonds. − The pioneer work has been documented by Dong and co-workers using Pd-catalyzed pyridine-directed C­(sp 2 )–H sulfonylation of 2-arylpyridine with sulfonyl chloride . Later, the same has been elegantly explored using different transition metals such as Pd, − Rh, Ru, , Cu, − and Ni , in the presence of various sulfonylating agents like sulfonyl chlorides or metal sulfinate salts etc.…”

Palladium‐Catalyzed C3‐Carbaldehyde Directed Regioselective C2‐Thioarylation of Indoles

“…[21] Quite recently, C2-chalocogenation of tryptophan-containing peptides by disulfides/diselenides was achieved by Sharma and co-workers using picolinamide as a directing group (Scheme 1c(ii)). [22] Here, we report the Pdcatalyzed sulfenylation of indoles with a C3-formyl group by disulfides in the presence of phenyl iododiacetate (Scheme 1c-(iii)).…”