Stereoselective β-mannosylation via anomeric O-Alkylation: Concise synthesis of β-D-Xyl-(l→2)-β-D-Man-(1→4)-α-D-Glc-OMe, a trisaccharide oligomer of the hyriopsis schlegelii glycosphingolipid

GRAPHICAL ABSTRACT

ABSTRACT

Synthesis of β-D-Xyl-(l→2)-β-D-Man-(1→4)-α-D-Glc-OMe (1), a tr-isaccharide oligomer of the Hyriopsis schlegelii glycosphingolipid is described. The synthesis involves a key β-mannosylation via cesium carbonate-mediated anomeric O-alkylation for direct synthesis of partially protected disaccharide β-D-Man-(1→4)-α-D-Glc-OMe (4) bearing a free C₂˭OH in the mannose moiety. In addition, a silver triflate-promoted glycosylation of 4 with 2,3,4-tri-O-benzoyl-α-D-xylopyranosyl bromide (5) followed by deprotection affords the desired trisaccharide component (1) of the Hyriopsis schlegelii glycosphingolipid.

KEYWORDS:

• β-mannosylation
• lactol
• anomeric O-alkylation
• glycosylation

Acknowledgements

We are grateful to National Science Foundation (CHE-1464787), The University of Toledo, and University of Michigan-Dearborn for supporting this research.

Additional information

Notes on contributors

Bishwa Raj Bhetuwal

Bishwa Raj Bhetuwal received his B.S. in chemistry in 2008 and M.S. in organic chemistry in 2014 from Tribhuvan University, Kathmandu, Nepal. He moved to the United States in the fall of 2015 and started his graduate studies in the Department of Chemistry and Biochemistry at The University of Toledo, Ohio. Since then, he has been working with Professor Jianglong Zhu as a graduate student research assistant on the development of new stereoselective glycosylation methods and synthesis of complex biologically significant oligosaccharides and glycoconjugates.

Xiaohua Li

Xiaohua Li received her B.S. in chemistry in 1998 from Tianjin University, Tianjin, China, and M.S. in Chemical Engineering in 2001 from Beijing Institute of Technology, Beijing, China. After that, she came to United States and did her Ph.D. studies under the supervision of Professor David Mootoo at Hunter College, CUNY, on the chemical synthesis of complex natural products. After working with Professor Samuel Danishefsky at Columbia University as a postdoctoral fellow, she joined University of Toledo, Ohio, as a Visiting Assistant Professor in 2010. In 2013, she started her independent career as an Assistant Professor of Chemistry at University of Michigan-Dearborn. Her current research interests focus on development of new chemical reactions and synthesis of biologically active molecules.

Jianglong Zhu

Jianglong Zhu received his B.S. in chemistry in 1998 and M.S. in organic chemistry in 2001 from Tianjin University, Tianjin, China. After receiving his Ph.D. in organic chemistry in 2007 from Boston University under the supervision of Professor John A. Porco, Jr, he worked with Professor Samuel Danishefsky as a postdoctoral fellow at Memorial Sloan-Kettering Cancer Center. In 2010, he joined Department of Chemistry and Biochemistry at The University of Toledo, Ohio, as an Assistant Professor. Dr. Zhu was promoted to Associate Professor in 2014 and to Full Professor in 2017. His current research interests include the development and application of new chemical methodologies in the synthesis of complex biologically important oligosaccharides and glycoconjugates as well as bioactive natural products.