ortho-Methoxycarbonylethynylphenyl Thioglycosides (MCEPTs): Versatile Glycosyl Donors Enabled by Electron-Withdrawing Substituents and Catalyzed by Gold(I) or Cu(II) Complexes

Abstract

With easily accessible and operator-friendly reagents, shelf-stable ortho-methoxycarbonylethynylphenyl thioglycosides were efficiently prepared. Based on these MCEPT glycoside donors, a novel glycosylation protocol featuring mild and catalytic promotion conditions with Au(I) or Cu(II) complexes, expanded substrate scope encompassing challenging donors and acceptors and clinically used pharmaceuticals, and versatility in various strategies for highly efficient synthesis of glycosides has been established. The practicality of the MCEPT glycosylation protocol was fully exhibited by highly efficient and scalable synthesis of surface polysaccharide subunits of Acinetobacter baumannii via latent–active, reagent-controlled divergent orthogonal one-pot and orthogonal one-pot strategies. The underlying reaction mechanism was investigated systematically through control reactions, leading to the isolation and characterization of the vital catalyst species in MCEPT glycosylation, the benzothiophen-3-yl-gold(I) complex. Based on the results obtained both from control reactions and from studies leading to the glycosylation protocol establishment, an operative mechanism was proposed and the effect of the vital catalyst species reactivity on the results of metal-catalyzed alkyne-containing donor-involved glycosylation was disclosed. Moreover, the mechanism for C-glycosylation side product formation from ortho-(substituted)ethynylphenyl thioglycoside donors with electron-donating substituents was also illuminated.

S-o-(p-Methoxyphenylethynyl)benzyl (SMPEB) Glycosides for Catalytic Glycosylation and Their Application in the Synthesis of Polyporus Umbellatus Polysaccharides

“…In recent years, catalytic glycosylation has attracted attention from glycoscientists using S -glycosides as donors. Au­(I)- or Cu­(II)-catalyzed glycosylation with thioglycosides as donors has been independently reported by Yu, Zhu, Zhang, and Sun . In regard to the metal-free catalytic glycosylation, Ragains and Li have respectively demonstrated that the glycosylation can be realized in the presence of Bronsted acids.…”

“…Au(I)-or Cu(II)-catalyzed glycosylation with thioglycosides as donors has been independently reported by Yu, 10 Zhu, 11 Zhang, 12 and Sun. 13 In regard to the metal-free catalytic glycosylation, Ragains 14 and Li 15 have respectively demonstrated that the glycosylation can be realized in the presence of Bronsted acids. Although breakthroughs have been achieved in catalytic activation of thioglycosides, the development of an efficient and catalytic glycosylation is still highly in demand with a readily accessible and easy-to-handle thioglycoside donor, especially a thioglycoside donor that can be catalyzed under metal-free conditions and enable effective glycosylation with a broad substrate scope.…”

Stereoselective AromaticO-Glycosylation of Glycosyl Chloride with Arylboronic Acid under an Air Atmosphere

“…The synthesis of aromatic O -glycosides has attracted plentiful attention, and various methods , have been developed after the first report in 1879 . The common method to form O -aryl glycosides remains using a phenol or phenoxide nucleophile displacing the leaving group from the anomeric position (Scheme a). − , Another classical method is the direct O -arylation of glycosyl hemiacetals with aryl halides or arylboronic acids, which always leads to no stereoselectivity (Scheme b,c). Recently, using arylboronic acids as an aromatic source oxidized by O 2 was applied in the glycosylation with 1,2-anhydrosugars and glycals to form O -aryl glycosides (Scheme d) .…”

Stereoselective Synthesis of the O‐antigen of A. baumannii ATCC 17961 Using Long‐Range Levulinoyl Group Participation

“…To date, more than 20 different A. baumannii polymeric saccharides have been elucidated among more than 90 serotypes [4] . In 2015, Nakamura reported the synthesis of the A. baumannii O18 tetrasaccharide; [5] in 2018, Wu disclosed the semi‐synthesis of a glyco‐conjugate vaccine of A. baumannii strain 54149 and found that pseudaminic acid (Pse) played a critical role in immunogenic activity; [6] in 2020, Gao demonstrated the synthesis of the A. baumannii K47 pentasaccharide using the α‐selective glycosylation method; [7] in 2021, Li and Chen described the synthesis of Pse‐CRM197 conjugates against A. baumannii Infection; [8] in the same year, Seeberger reported the synthesis of the trisaccharide repeating unit of A. baumannii AB5075; [9] one year later, Seeberger published an amazing work on synthetic carbohydrate‐based vaccines against A. baumannii 17978; [10] Yang and Yin reported the chemical synthesis and antigenic evaluation of inner core oligosaccharides of A. baumannii ; [11] recently, Sun described the synthesis of the tetrasaccharide subunit of A. baumannii SMAL, the nonasaccharide of the A. baumannii O22 and the tetrasaccharide fragment of A. baumannii ATCC 17961 [12] . The A. baumannii ATCC 17961 O‐antigen consists of pentasaccharide repeating unit (with core trisaccharide subunit [→6)‐β‐ d ‐Glc(1→3)‐β‐ d ‐GalNAc(1→3)‐α‐ d ‐Gal(1→], β‐linked to a 2,3‐diacetamido‐ d ‐glucuronate at C4‐OH of Gal and β‐linked GlcNAc at C6‐OH of Gal) (Figure 1).…”