C-Difluoromethylene-containing, C-trifluoromethyl and C-perfluoroalkyl carbohydrates. Synthesis by carbohydrate transformation or building block methods

Reactions of Difluoroenoxysilanes with Glycosyl Donors: Synthesis of Difluoro-C-glycosides and Difluoro-C-disaccharides

“…[2] It was not surprising that carbohydrate chemists were interested in applying this concept to synthesize various substituted fluorinated sugars and nucleosides. [3] Though several groups reported on C-difluoromethylene containing groups grafted in other positions, [4] the grafting on the anomeric carbon to give difluoro-C-glycosides, was much less investigated, in spite of the potential interest of these compounds as non hydrolyzable glycoside mimics. Most of the methods of synthesis of C-glycosides, recently reviewed, [5] are not suitable for difluoro-C-glycosides, which need more specific methodologies.…”

Modified natural substances—fluorinated and fluoroalkylated monosaccharides and inositols

“…C-Difluoromethylene-containing and C-trifluoromethyl and C-perfluoroalkyl substituted carbohydrates (see the recent review [5]) are attractive moieties in physiologically interesting glycosides, because the strong electron-withdrawing group in 2-position also stabilises the neighboured anomeric centre. Therefore, glycosides and nucleosides derived from non-natural carbohydrates, especially from 2-C-trifluoromethyl substituted pentoses, are of current interest [36][37][38][39] O-difluoromethyl-substituted carbohydrates could be useful tools, e.g.…”

“…Nevertheless, the interest in fluorinated analogues of natural substances is increasing continuously [2][3][4][5], since fluorine, strategically positioned in target molecules, may greatly modify the chemical properties, the biological activity and selectivity of those molecules. Lipophilicity is an important consideration in the design of biologically active compounds since it often controls absorption, transport, or receptor binding.…”

Synthetic Methods for Heterocycles and Carbocycles Bearing Fluorinated One-Carbon Units (=CF₂, CHF₂, or CF₃): Intramolecular Reaction of 2-Trifluoromethyl-1-alkenes

“…2 (i) The incorporation of a trifl uoromethyl (CF 3 ) group into an organic molecule increases its lipophilicity and affects its electron density. 3 (ii) The difl uoromethyl (CHF 2 ) group is a hydrogen bond donor without nucleophilicity and with high lipophilicity, 4 making it a special mimic of a hydroxy group ( Figure 1a).…”

“…Multiple issues hinder these synthetic developments, including synthetic problems in the regioselectivity for the introduction of these units, the necessity of multistep procedures, and the diffi culty of handling reagents for their introduction. 9 In particular, to introduce CHF 2 and CF 2 groups, there are only limited methods available.…”