Divergent Entry to C-Glycosides from Unprotected Sugars

Abstract

An efficient, divergent, and straightforward access to novel C-glycosides has been developed, namely, α-hydroxy carboxamide and carboxylic acid derivatives, via a green and scalable process from unprotected carbohydrates. The method involves condensation of 1,3-dimethylbarbituric acid with unprotected sugars followed by subsequent barbiturate oxidative cleavage in the same pot. Further expanding of the chemistry led to the development of efficient entries to diastereoisomerically pure C-glycosyl-α-hydroxy esters or amides through nucleophilic attack on a readily available and versatile key lactone intermediate.

Reverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids

“…Equilibrium on the YeiN reaction far on the side of the C-nucleoside monophosphate, which would seem unusual for a nominal glycosidase reaction, is thus explained. Enzymatic C-C coupling reactions are synthetically important in the carbohydrate sciences 65,[78][79][80][81][82][83][84][85][86] and the current study adds new application-relevant feature to them.…”

Supramolecular carbohydrate-based hydrogels from oxidative hydroxylation of amphiphilic β-C-glycosylbarbiturates and α-glucosidase-induced hydrogelation

“…25 A previous work from the L′Oréal group reported that H 2 O 2 -mediated oxidative hydroxylation of 1′ in water led in a one-pot procedure to β-methylamide C-glucoside derivative 4′ with the release of NaOH in the mechanism pathway. 26 Moreover, a patent from the previous authors showed that oxazolidine-2,4-dione intermediates 3 and 3′ could be favoured by controlling the reaction time or by using Oxone® as an oxidizing reagent for 16 h. 27 For the latter, by reducing the reaction time from 16 to 2 h, the C-5 hydroxyl derivative 2′ was obtained in 71% yield. And compound 2 was not described.…”

“…25 A previous work from the L′Oréal group reported that H 2 O 2 -mediated oxidative hydroxylation of 1′ in water led in a one-pot procedure to β-methylamide C -glucoside derivative 4′ with the release of NaOH in the mechanism pathway. 26…”

The synthesis of oligomers containing alternating C-glycosyl α-amino acids and proteinogenic α-amino acids

“…Methodologies developed for the synthesis of C-glycosyl a-amino acids include alkylation of a-amino acid equivalents, Strecker reactions, hydrogenation of dehydroamino acids, multicomponent reactions with sugar derivatives, and de novo synthesis of C-glycosyl amino acids. [6][7][8][9][10] Also, olefin cross-metathesis/cyclization strategy, 11 condensation of barbituric acid with unprotected carbohydrates followed by subsequent barbiturate oxidative cleavage 12 and Nicatalysed reductive hydroglycosylation of alkynes 13 were employed. Although often reliable, these methods suffer from multistep synthetic procedures, harsh reaction conditions, and limited substrate scope, accompanied with poor control of stereoselectivity.…”

“…Novel, mild alternatives include photo-catalysed addition of glycosyl radicals to α-imino esters 14 and photo-induced Cu-catalysed asymmetric C(sp 3 )–H alkylation of glycine derivatives, 15 but purification of such radical reactions could be difficult and often hinder scale-up. Despite developed methodologies, most of published data refer to amino acids with carbohydrate unit placed at the side-chain, 10,13,16 or C -glycosyl β-amino acids, 8,9,11,16 b while examples with C -glycosyl α-amino acids with carbohydrate unit placed directly to Cα atom, 12,14,15 or C -glycosyl γ-amino acids are scarce 17 (Fig. 1A).…”