Total Synthesis of Aryl C-Glycoside Natural Products: Strategies and Tactics

Abstract

The aryl C-glycoside structure is, among the plenty of biologically active natural products, one of the distinct motifs embedded. Because of the potential bioactivity as well as the synthetic challenges, these structures have attracted considerable interest, and extensive research toward the total synthesis has been performed. This Review focuses on the synthetic strategies and tactics employed in the total synthesis of this class of natural products. The Introduction describes the historical background, structural features, and synthetic problems associated with aryl C-glycoside natural products. Next the Review summarizes the methods for constructing the aryl C-glycoside bonds. Completed total syntheses-and, in some cases, selected examples of incomplete syntheses-of natural aryl C-glycosides are also summarized. Finally described are the strategies for constructing polycyclic structures, which were utilized in the total syntheses.

Pd-catalyzed coupling reactions of anhydro-aldose tosylhydrazones with aryl bromides to produce substituted exo -glycals

“…Other ligands such as SPhos, RuPhos and P(4-F-C 6 H 4 ) 3 were found to be also effective (entries 3-5, respectively), however, the yield did not improve significantly. On the other hand, P(2-furyl) 3 proved ineffective in this reaction (entry 6). It was observed that 4 mol% of CataCXium A gave the better result both in short and longer times (entries 7 and 8), however, application of 10 mol% did not affect the yield (entry 9).…”

“…Optimal reaction conditions were sought for by applying literature conditions [25] to tosylhydrazone 1 [26][27][28] and bromobenzene (1,4-dioxane, 70 o C with 2 mol% tris(dibenzylideneacetone)dipalladium(0) (Pd 2 (dba) 3 ) catalyst in the presence of LiOtBu and XPhos, Table 1). Both short and longer reaction times resulted in moderate yields with the XPhos ligand (entries 1 and 2).…”

“…Formation of a carbon-carbon bond at the anomeric position of carbohydrates has received great attention due to the versatile applicability of such sugar derivatives as chiral synthons in syntheses of complex natural products as well as to manyfold biological activities of Cglycosyl compounds [1][2][3]. As a part of a program targeting the systematic study of applications of anhydro-aldose tosylhydrazones (compounds H in Scheme 1) as coupling partners in metal-free [4,5] and transition metal-catalyzed coupling reactions we have been interested in the Pd-catalyzed coupling of H with bromobenzenes.…”

Stereocontrolled Synthesis of 2‐Fluorinated C‐Glycosides

“…A number of successful pharmaceuticals contain this structural feature, including a series of SGLT‐2 inhibitors such as Dapagliflozin ( 1 ) . It is also important to note that the aryl C ‐glycoside motif is found in numerous natural products, including Carminic acid ( 2 ) and Papulacandin D ( 3 ). Whilst this approach is logical, the intrinsic challenges associated with the generation of crowded, often quaternary, stereocentres must be considered.…”

Reengineering Chemical Glycosylation: Direct, Metal‐Free Anomeric O‐Arylation of Unactivated Carbohydrates

“…Indeed, ar ecent survey conducted by Njardarson and co-workers of U.S. FDA-approved drugs containing oxygen heterocycles revealedt hat pyranoses and furanoses are the top two most frequently employed motifs. [12] Predicated on retrosynthetic analysiso ft he anomeric Csp 3 ÀO bond ( Figure 1, upper centre, disconnection A), ap lethora of protocols for aromatic O-glycosylation has been developed. [11] Consequently,s trategies to facilitatet he efficient synthesis of diversea ryl glycosides have been intensively pursued.…”