Kobayashi, Daishiro published the artcilePeptide cyclization mediated by metal-free S-arylation: S-protected cysteine sulfoxide as an umpolung of the cysteine nucleophile, Application In Synthesis of 151-10-0, the main research area is cyclic stapled peptide synthesis; solid phase peptide synthesis oxidative cyclization cystein sulfoxide arylation; thioether linkage formation reaction mechanism sulfoxide tryptathionine; aromatic electrophilic substitution; S-arylation; peptide cyclization; stapling; sulfoxides; tryptathionine.
Covalent linking of side chains provides a method to produce cyclic or stapled peptides that are important in developing peptide-based drugs. A variety of crosslinking formats contribute to fixing the active conformer and prolonging its biol. activity under physiol. conditions. One format uses the cysteine thiol to participate in crosslinking through nucleophilic thiolate anions or thiyl radicals to form thioether and disulfide bonds. Removal of the S-protection from an S-protected Cys derivative generates the thiol, which functions as a nucleophile. S-Oxidation of a protected Cys allows the formation of a sulfoxide that operates as an umpolung electrophile. Herein, the applicability of S-p-methoxybenzyl Cys sulfoxide (Cys(MBzl)(O)) to the formation of a thioether linkage between tryptophan and Cys has been investigated. The reaction of peptides containing Cys(MBzl)(O) and Trp with trifluoromethanesulfonic acid (TFMSA) or methanesulfonic acid (MSA) in TFA in the presence of guanidine hydrochloride (Gn · HCl) proceeded to give cyclic or stapled peptides possessing the Cys-Trp thioether linkage. In this reaction, strong acids such as TFMSA or MSA are necessary to activate the sulfoxide. Addnl., Gn · HCl plays a critical role in producing an electrophilic Cys derivative that combines with the indole by aromatic electrophilic substitution. The findings led us to conclude that the less-electrophilic Cys(MBzl)(O) serves as an acid-activated umpolung of a Cys nucleophile and is useful for S-arylation-mediated peptide cyclization.
Chemistry – A European Journal published new progress about Arylation. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Application In Synthesis of 151-10-0.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem