Organocatalytic synthesis of carbohydrates

Abstract

The key role of carbohydrates in biological processes and their visible existence in our everyday life have stimulated the interest of leading research groups on the smart and simple synthesis of common and rare sugar molecules. Now, more than 120 years after Fischer's first synthesis of (D)-glucose (1890), we are witnessing important development in this field of total synthesis. Using modern methods of direct activation of carbonyl compounds chemists can prepare sugars in an elegant and efficient way similar to that of Nature. This tutorial review presents recent impressive progress in the area of de novo synthesis of carbohydrates by using organocatalytic direct aldol reaction as a key step.

Asymmetric syn‐Aldol Reaction of α‐Hydroxy Ketones with Tertiary Amine Catalysts

“…[2] Since the first reports of metal-complex- [3] and proline-catalysed direct asymmetric aldol reactions, [4] numerous catalysts have been designed that have further improved the catalyst reactivity, enantioselectivity and most importantly substrate scope of this reaction. [6] Since 2000, few initial reports have addressed the direct aldol addition of hydroxy ketones to aldehydes by using both organometallic and proline catalysts (Scheme 1). This newly elaborated tertiary-amine-catalyzed direct asymmetric aldol reaction has extended the scope of organocatalytic processes to aromatic α-hydroxy ketones, which have hitherto been unreactive towards enamine catalysis.…”

Asymmetric assembly of aldose carbohydrates from formaldehyde and glycolaldehyde by tandem biocatalytic aldol reactions

“…However, this requires cumbersome successive protection and deprotection steps 9 . Alternatively, straightforward and efficient bottom-up strategies for the de novo construction of polyoxygenated scaffolds may be devised through the consecutive connection of small building blocks, by C-C bond-forming reactions with the concomitant installation of hydroxylated chiral positions 3,10 . The catalytic asymmetric aldol addition reaction has proved to be an extremely useful carboligation procedure for the generation of polyoxygenated molecules [10][11][12] .…”

“…Alternatively, straightforward and efficient bottom-up strategies for the de novo construction of polyoxygenated scaffolds may be devised through the consecutive connection of small building blocks, by C-C bond-forming reactions with the concomitant installation of hydroxylated chiral positions 3,10 . The catalytic asymmetric aldol addition reaction has proved to be an extremely useful carboligation procedure for the generation of polyoxygenated molecules [10][11][12] . When aiming to recreate the prebiotic synthesis of sugars, simple amino acids and inorganic catalysts were found to assemble glycolaldehyde (1a) and formaldehyde (1b) into diverse carbohydrates, thereby offering partial control over the sugar size, configuration and enantiomeric ratio 13,14 .…”

Synthesis of Structurally Complex Silicon Frameworks through the First Sila‐Aldol Reaction

“…[2][3][4][5] These synthetic approaches include,f or example, the use of organocatalysts (amine-based systems), [4,6] chiral auxiliaries (Evans oxazolidinone route), [7] as well as chiral Lewis acids (e.g., Zn, Ag, Pd, and Cu complexes) [4,5,8] and bases. [1] On the basis of this general strategy,namely the merging of two carbonyl compounds,s ynthetic chemists have put al ot of emphasis on stereoselective aldol reactions over the last couple of centuries to accomplish results comparable to those achieved by organisms and enzymes in nature.…”