Synthesis of 2-Thiocarbohydrates and Their Binding to Concanavalin A.

A convenient and general synthesis of 2-thiocarbohydrates via cerium ammonium nitrate oxidation of the thiocyanate ion is described. Radical addition to glycals proceeds with excellent regio- and good stereoselectivities in only one step, deprotection affords water-soluble 2-thio saccharides. Binding studies to Con A have been performed by isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR spectroscopy. The 2-thiomannose derivative binds even stronger to Con A than the natural substrate, offering opportunities for new lectin or enzyme inhibitors.

Carbohydrate-2-deoxy-2-phosphonates: simple synthesis and Horner-Emmons reaction.

Phosphorus meets carbohydrates: Dimethyl phosphite reacts with ceric(IV) ammonium nitrate (CAN) to give phosphonyl radicals that add to glycals 1. The derivatives 2 were isolated in high yields and during a subsequent Horner-Emmons reaction underwent an interesting elimination to give 3,6-dihydro-2H-pyrans 3. The short sequence with simple precursors is applicable to the transformation of hexoses, pentoses, and disaccharides. Bn = benzyl.

Remarkable oxidation stability of glycals: excellent substrates for cerium(IV)-mediated radical reactions.

The remarkable stability of glycals under oxidative conditions becomes apparent by their redox data in solution, computed HOMO energies, and behavior on the addition of electrophilic radicals generated in the presence of cerium(IV) ammonium nitrate. Oxidation potentials up to 2.03 V vs ferrocene were obtained, which are exceptionally high for cyclic enol ethers but correlate nicely with the reaction times of the radical reactions. Protecting groups have a strong influence on the oxidation stability and HOMO energies of glycals as E(ox) is shifted from O-silyl over O-benzyl to O-acetyl by more than 500 mV. Interestingly, this effect must be transmitted through sigma-bonds, even up to the para-position of a benzoate group, as verified by a wide variation of remote substituents in the carbohydrate. Favorable interactions of the sigma*-orbital of the adjacent C-O bond with the HOMO of the double bond are proposed as a mechanistic rationale, which might be important for the redox behavior of other allylic systems. Finally, donors and acceptors in the 1-position exert the strongest influence on the oxidation stability, shifting the potentials by almost 1 V and resulting in different follow-up reactions of the cerium(IV)-mediated additions of malonates. It is the remarkable oxidation stability of glycals that makes them valuable building blocks in carbohydrate chemistry.

Convenient synthesis of branched-chain glycosamines by radical addition of nitromethane to glycals.

Radical addition-reduction-acetylation is the simple three-step sequence for the synthesis of branched-chain glycosamines 3 from glycals 1 and nitromethane (2). The intermediary formed 2-C-nitromethyl-pyranosides are valuable precursors for the synthesis of C-2 branched disaccharides.