Selective acylation and transformation of unprotected monosaccharides

Abstract

In this thesis, we will demonstrate the application of site-selective acylation of saccharides for the precise synthesis of bioactive molecules which have practical applications in the pharmaceutical industries. The methods presented provide a highly concise and efficient pathway to access challenging site-specific functionalized saccharide moieties, facilitating drug discovery and enhancing manufacturing routes for commercially available drugs. In chapter 1 of this thesis, we will briefly introduce the significance of saccharides, the challenges associated with utilizing them, the key strategies previously employed to achieve regioselective acylation of saccharides and the available transformations of acyl bonds in saccharide derivatives. In chapter 2 of this thesis, we will demonstrate the site-selective acylation of unprotected monosaccharides with the aid of NHCs. This site-selective strategy utilizes NHCs and boronic acid to provide layers of differentiation for precise acylation and ‘mix and match’ combinations to achieve a variety of desired outcomes. Under this unique and mild strategy, a variety of saccharides, aldehydes, carboxylic acid, and esters are tolerated. Practical applications for this strategy have been applied for the synthesis of bioactive molecules. In chapter 3 of this thesis, we will demonstrate the applications of site-selective acylation of unprotected monosaccharides through a ‘tagging and editing’ strategy for the access of rare sugars and C-glycosides. This strategy integrates site-selective acylation of photoredox glycosyl esters and photocatalysis to form glycosyl radicals, which could be trapped by alkenes or HAT catalyst to afford C-glycosides and rare sugars, respectively. Our method demonstrates good tolerance to a wide range of functional groups and has been successfully applied in the post-transformation of drug molecules and the preparation of C‑glycosyl amino acids. In chapter 4 of this thesis, we will demonstrate the site-selective acylation of naturally abundant and readily available natural monosaccharides through Sn2 Mitsunobu reaction to generate bench stable glycosyl esters. Under photoredox conditions, this glycosyl ester can undergo Giese-type additions for the construction of C-C bonds to yield a wide variety of C glycosides with excellent stereoselectivity. Our method demonstrates good tolerance to a wide range of functional groups and has been successfully applied in the post-transformation of drug molecules and the preparation of C‑glycosyl amino acids. In chapter 5 of this thesis, we will conclude our work from the previous chapters and provide insight into future work that can be done with regards to the site-selective acylation of saccharides and their acyl groups for further transformations.