Thioether protection via selectively cleavable sulfonium salts

Synthesis of O-1–O-6 Substituted Positional Isomers of d-Glucose–Thioether Ligands and Their Ruthenium Polypyridyl Conjugates

“…This same intermediate was also observed in the presence of a mild reducing agent such as Et 3 SiH. However, when this intermediate was treated with MeNH 2 in MeOH, the methyl thioether could be liberated, acquiring hemiacetal H37 in five steps (18% overall yield). After reaction of this compound with [Ru­(tpy)­(bpy)­(H 2 O)]­(PF 6 ) 2 glycoconjugate [Ru­(tpy)­(bpy)­( 37 )]­PF 6 , ([6]­PF 6 ) was acquired instead of [Ru­(tpy)­(bpy)­( H37 )]­(PF 6 ) 2 .…”

Preparation of Multifunctional and Multireactive Polypeptides via Methionine Alkylation

“…This result is not surprising because in all previous work on methionine alkylation using amino acids, peptides, or proteins there are no reports of sulfonium formation using unactivated reagents. [16][17][18][19][27][28][29][30][31]42 To expand further the scope of poly-(Met) alkylation, explored different means to increase the reactivity of unactivated alkyl halides. Silver tetrafluoroborate is known to promote thioether alkylation in small molecules, 45,46 and we found that the addition of this reagent to alkylations in acetonitrile promoted the complete reaction of poly(Met) with unactivated alkyl halides (e.g., haloethyl compounds) (Figure 3).…”

“…Because of its role in biology, the alkylation of thioether groups in methionine has been studied for some time, with pioneering studies being done by Toennies in the 1940s. , The majority of work in this area has employed simple alkylating agents, such as iodomethane to give the naturally occurring, dietary supplement S -methyl-methionine, , as well as iodoacetic acid to form soluble derivatives and probe the active sites of proteins. − There are some reports on the use of other activated alkyl halides to alkylate methionine, including those containing alkene and alkyne groups, yet no reactions were performed on the resulting sulfonium derivatives. − Katchalski was the first to alkylate poly( l -methionine), poly(Met), preparing both methyl and carboxymethyl sulfonium derivatives from the corresponding alkyl bromides and poly(Met) in neat formic acid . These polysulfoniums were found to be stable and water-soluble and were studied for their conformational and polyelectrolyte behavior.…”

Reversible chemoselective tagging and functionalization of methionine containing peptides

“…9 This work was based on the pioneering studies of Met alkylation in proteins, which were mainly focused on use of non-functional alkylating reagents to probe inhibition of enzyme active sites. [10][11][12][13][14] While many of these alkylations were reported to be irreversible, [10][11][12] some studies, 13,14 as well as subsequent experiments with peptides, [15][16][17][18][19][20] found that Met alkylation can be reversed under certain conditions. Since each study typically employed a different substrate (amino acid, peptide or protein), different alkylating reagents, and different nucleophilic cleavage reagents, [10][11][12][13][14][15][16][17][18][19][20] comparison of reactivity and properties of the various alkylated Met sulfonium groups that have been reported is challenging.…”