Scientists from the Zelinsky Institute have developed a stereoselective method for 1,2-cis-glucosylation
Fragments of 1,2-cis-linked glucose are a part of many biologically significant oligosaccharides. Traditionally, glucosyl donors containing a non-participating 2-O-benzyl protecting group are used to prepare such structures. However, the removal of O-benzyl protecting groups by hydrogenolysis is not trivial in the presence of an azido group in aglycone, which is necessary for the synthesis of neoglycoconjugates.
Researchers from the Laboratory of Glycochemistry of the Zelinsky Institute have synthesized new glycosyl donors based on glucopyranose with one or two triisopropylsilyl (TIPS) groups that do not contain benzyl fragments. The resulting compounds were used to study the stereoselectivity of α-glucosylation. It has been established that glycosylation of phenyl-3,4,6-tri-O-benzoyl-2-O-TIPS-1-thio-b-D-glucopyranoside (1) with one TIPS group at O-2 is highly stereoselective (a/b ≥ 10:1), while the use of a glycosyl donor containing two TIPS groups at O-2 and O-3 leads to a loss of a-stereoselectivity (a/b = 3:1). The study revealed the dependence of the result of a-glucosylation on the nucleophilicity of a number of glycosyl acceptors. Full α-stereocontrol of glycosylation with 2-O-TIPS containing glucosyl donor 1 is achieved by glycosylation of weak nucleophiles. In this case, glucosylation appears to follow an SN1-like route through the glycosyl cation anchored in the 4H3 conformation, in which the bulky TIPS group at O-2 occupies a pseudo-equatorial position. The results obtained are an important contribution to the development of efficient and stereoselective methods for the synthesis of a wide range of glycoconjugates.
Source:
Polina I. Abronina, Nelly N. Malysheva, Alexander I. Zinin, Natalya G. Kolotyrkina, Leonid O. Kononov Stereocontrolling Effect of a Single Triisopropylsilyl Group in 1,2-cis-Glucosylation. Eur. J. Org. Chem., 2022, e202200517. DOI: 10.1002/ejoc.202200517.