Cyanide-Free Synthesis of Glycosyl Carboxylic Acids and Application for the Synthesis of Scleropentaside A

Abstract

We have developed a cyanide-free strategy for the synthesis of glycosyl carboxylic acids, which can provide 1,2-trans or 1,2-cis glycosyl carboxylic acids and is compatible with common protecting groups. The synthetic utility was demonstrated by the synthesis of 12 unreported glycosyl acids and the total synthesis of scleropentaside A.

Efficient Copper‐Catalyzed Highly Stereoselective Synthesis of Unprotected C‐Acyl Manno‐, Rhamno‐ and Lyxopyranosides

“…[19][20][21] In all cases, the glycosyl donors for these strategies have to be synthesized in lengthy multi-step routes. While C-acyl glycosides have recently gained interest as synthetic intermediates and in drug discovery, [22][23][24][25][26][27][28][29][30][31][32] syntheses of C-acyl d-mannopyranosides have remained scarce and syntheses of unprotected C-acyl manno-type pyranosides were not reported at all. [23,24,26,31] To date, most syntheses of C-glycosidic compounds revolve around benzyl-protected d-mannopyranosyl cyanides 4 b.…”

“…If esters are employed as protective groups, the 2-OR substituent is eliminated in an E1 cb -elimination when deprotection under alkaline conditions is attempted. This unwanted reaction was reported to occur with pivaloyl, [32] acetyl [23,24] and benzyl [25][26][27][28][29][30][31] protecting groups. This problem is especially pronounced with peracetylated C-acyl α-d-mannopyranosides 8α where this elimination already occurs during purification by column chromatography.…”

“…[ 19 , 20 , 21 ] In all cases, the glycosyl donors for these strategies have to be synthesized in lengthy multi‐step routes. While C ‐acyl glycosides have recently gained interest as synthetic intermediates and in drug discovery,[ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] syntheses of C ‐acyl d ‐mannopyranosides have remained scarce and syntheses of unprotected C ‐acyl manno‐type pyranosides were not reported at all. [ 23 , 24 , 26 , 31 ]…”

Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes

“…Besides, the complex functionality of peptides are poorly tolerated with the glycosylation conditions. In recent years, transition metal-catalyzed C -glycosylation has gained great attention 26 – 43 and a large variety of C -glycoside natural products as well as drug candidates have been successfully synthesized 44 – 49 . However, synthesis of complex C -glycosyl peptides, especially a convergent synthesis using oligosaccharides as donors still poses a formidable challenge, due to the following methodological limits: (i) scarcity of methods for construction of alkyl/alkenyl C -glycosidic bonds, in contrast to the well-studied aryl C -glycosylation; (ii) harsh reaction conditions, including high temperature, strong bases, stoichiometric amount of organometallic reagents, or metal additives that are poorly compatible with peptide substrates; (iii) use of large excess of sugar donors and/or insufficient anomeric selectivity, impeding convergent synthesis with expensive oligosaccharide donors; (iv) use of highly functionalized sugar donors, necessitating multistep transformations to procure the final glycopeptides.…”

1,2-trans-Stereoselective Synthesis of C-Glycosides of 2-Deoxy-2-amino-sugars Involving Glycosyl Radicals

“…In a continuation of our interest in the synthesis of C -glycosides, , we report herein a general, toxic-reagent-free approach for the synthesis of C -alkyl glycosides of 2DASs. Complementary to previous strategies, the reaction is 1,2- trans -selective and could be applied to not only alkenes with electron-withdrawing groups but also aryl alkenes.…”