Glycosyl Disulfides:  Novel Glycosylating Reagents with Flexible Aglycon Alteration

Abstract

[reaction: see text] Glycosyl disulfides have been shown for the first time to be effective glycosyl donors. Glucosylation and galactosylation of a panel of representative alcohol acceptors allowed the formation of 28 simple glycosides, disaccharides, and glycoamino acids in yields of up to 90%. As well as providing a novel class of effective glycosyl donors, the ability to easily alter the nature of the aglycon and the ability to differently activate donors that differ only in their aglycon simply through altering conditions lends glycosyl disulfide donors to their use in latent-active reactivity tuning strategies.

Crystal and molecular structures of diglycosyl disulfide derivatives

“…The disulfide torsion angle (C1-S1-S2-C21) is close to 90°, the value regularly observed in unrestricted acyclic disulfides. [13][14][15] Similar values have been reported from X-ray determination of alkyl-glycosyl disulfide structures with either furanosyl-4 or pyranosyl 16 rings. Importantly, the helicity of the S-S-bond is M (Fig.…”

New Principles for Glycoside‐Bond Formation

“…Since no single method is universally applicable and able to address all the issues associated with glycoside-bond formation, many other glycosyl donors, such as telluroglycosides, [130] glycosyl carbonates, [131] various heteroaryl glycosides, [15,[21][22][23][24][25]132] various N-substituted glycosyl carbamates, [133] methyl 3,5-dinitrosalicylate (DISAL) glycosides, [134,135] glycosyl disulfides, [136] glycosyl sulfimides, [137] N-glycosyl amides, [138] glycosyl phthalates, [139] 2-allyloxyphenyl glycosides, [140] glycosyl 5-hexynoates, [141] and propargyl glycosides [142] have also been devised in the past decade. Furthermore, the development of new activation systems for existing donors propels carbohydrate chemistry forward.…”

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

“…10,[21][22][23][24][25][26][27][28][29][30][31] Another thiol-based method, the selective formation of mixed disulfides, is both one of the oldest and most enduring of ligation methods. 1,2,[32][33][34][35][36][37][38] The mildness of the disulfide ligation and its established chemoselectivity for the cysteine thiol in the presence of all the proteinogenic amino acids stands in stark contrast to the various other methods for cysteine functionalization, most of which involve the capture of the cysteine thiol by electrophilic species, and which consequently have obvious potential chemoselectivity issues. 1,2,39 The practicality of the disulfide ligation, with its direct applicability to cysteine-containing peptides, also contrasts with the various ingenious indirect methods that have been developed for the preparation of S-functionalized cysteine derivatives, 17 including, for example, the Michael addition of thiols to dehydroalanine units, 40 the alkylation of thiolates with peptide-based β-halo-alanine units, [41][42][43] and other electrophiles, 44,45 the opening of peptide-based aziridines by thiolates, 46,47 and the synthesis of peptides with previously functionalized cysteine building blocks, [48][49][50] each of which requires the synthesis of modified peptides.…”