Development of Glycosylation Using the Glucopyranose 1,2-Orthobenzoate under Electrochemical Conditions

Abstract

Substituted glucopyranose 1,2-orthobenzoate undergoes β-selective glycosylation. The developed orthobenzoate derivative was stable under standard workup conditions and efficiently provided a variety of glycosides by EGA (electrogenerated acid), produced by anodic oxidation of cyclohexanol. Upon comparison with Lewis and Brønsted acids, EGA superiorly affected activation of the orthoester to afford desired glycosides possessing such aglycons as sugars, steroids, and adamantanes.

Glycosylation of a Newly Functionalized Orthoester Derivative

“…Although removal of the TBS group in the benzylic region provided the stable phenol derivative 4 [14], the triol was labile under standard work-up conditions, and only detected by ESI mass spectrum. These observations prompted us to synthesize the orthoester derivative 2a, in which a protecting group at the C-6 position can be selectively removed.…”

“…When the orthoester 2a was submitted to reaction with cyclohexanol in the presence of EGA [14] and 4Å MS in 1,2-DCM at 40 °C, the expected β-glycoside 7 was obtained in 62% yield (Scheme 2). Next selective removal of the Fmoc group in 7 under basic conditions was carried out to give 8 in 95% yield, without any acyl migration from C-4 to C-6 position or removal of the acyl group.…”

“…Orthoesters were known to be converted to the corresponding glycosides under acidic conditions, and relatively stable derivatives were employed as glycoside precursors by Kochetkov [7][8][9][10][11] and Kunz [12,13]. We reported the synthesis and reaction of the orthoester 1 (Figure 1), which could be purified by silica gel column chromatography and kept for one month at room temperature [14]. Upon glycosylation with appropriate alcohols in the presence of the OPEN ACCESS electrogenerated acid (EGA) [15][16][17][18][19][20], which is considered to be anhydrous HClO 4 produced by anodic oxidation of cyclohexanol and Bu 4 NClO 4 , the corresponding glycosides were produced in high (primary OH) to moderate (secondary OH) yields, even on tertiary OH groups [14].…”

“…We reported the synthesis and reaction of the orthoester 1 (Figure 1), which could be purified by silica gel column chromatography and kept for one month at room temperature [14]. Upon glycosylation with appropriate alcohols in the presence of the OPEN ACCESS electrogenerated acid (EGA) [15][16][17][18][19][20], which is considered to be anhydrous HClO 4 produced by anodic oxidation of cyclohexanol and Bu 4 NClO 4 , the corresponding glycosides were produced in high (primary OH) to moderate (secondary OH) yields, even on tertiary OH groups [14]. Upon comparison with Lewis acids and Brønsted acids, EGA provided better results in glycosylation reactions.…”

Chemical Glycosylation by Single Electron Transfer

“…[26] Nishiyama and co-workers developed glucopyranose 1,2-orthobenzoate 32 as ag lycosyl donor for EGA-promoted glycosylation (Scheme 4). [27] In this case,t he choice of Bu 4 NClO 4 as an electrolyte could be important to generate anhydrous HClO 4 ,w hich has already been reported as an EGA. 5Challenges in Chemical Glycosylations by SET…”