Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis ofC‐linked Glycoconjugates

Abstract

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available,air and moisture stable precursors to glycosyl radicals.These glycosyl sulfoxides could be converted to glycosyl radicals by way of arapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex Clinked glycoconjugates under mild conditions.T his reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate-DNA conjugates. Scheme 1. a) Glycosyl radicals as valuable intermediates in C-glycoside synthesis. b) Our strategy to generate glycosyl radicals.

Highly (E)-Selective Trisubstituted Alkene Synthesis by Low-Valent Titanium-Mediated Homolytic Cleavage of Alcohol C–O Bond

“…2 These new applications include amino acid 3 and carbohydrate−DNA conjugate syntheses. 4 Reactions between carbon radicals and alkenes generate another radical species that are used in further radical transformations. This feature allows the design of customized sequences of radical reactions that can forge multiple C−C bonds and introduce additional functional groups in a single step.…”

Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes

“…However, synthesis of complex C -glycosyl peptides, especially a convergent synthesis using oligosaccharides as donors still poses a formidable challenge, due to the following methodological limits: (i) scarcity of methods for construction of alkyl/alkenyl C -glycosidic bonds, in contrast to the well-studied aryl C -glycosylation; (ii) harsh reaction conditions, including high temperature, strong bases, stoichiometric amount of organometallic reagents, or metal additives that are poorly compatible with peptide substrates; (iii) use of large excess of sugar donors and/or insufficient anomeric selectivity, impeding convergent synthesis with expensive oligosaccharide donors; (iv) use of highly functionalized sugar donors, necessitating multistep transformations to procure the final glycopeptides. Recently, Chen 50 , Niu 51 , Ackermann 52 , 53 , Liu 54 , Wang 55 , and co-workers have disclosed a series of methods for the synthesis of C -glycosyl amino acids via either C–H activation or radical addition strategies. Very recently, Wang et al reported a stereodivergent synthesis of C -glycosamino acids using glycal donors via Pd/Cu dual catalysis 56 .…”