A class of mammalian proteins known as Galectins is distinguished by its capacity to bind to β-d-galactosides. In order to increase drug-like qualities, several researchers have discovered new Galectin-3 disaccharide mimics. They discovered that one of the monosaccharide subunits may be substituted with an appropriately functionalized tetrahydropyran ring. Strong Galectin-3 inhibitors were found by optimizing the structure-activity correlations around a tetrahydropyran-based scaffold. CD BioGlyco provides Glycobiology Microarray Platforms such as Lectin Microarray Assay to study the binding ability of mimics, and other services like Custom Carbohydrate Synthesis for customers to help them produce tetrahydropyran-based thio-disaccharide mimics.
Recent developments include the synthesis of new aryltriazole-containing thio-disaccharide analogues and the creation of tetrahydropyrano-side-structured galactose derivatives. This is a precise synthesis technique shown below: The intermediate 225 was made via trifluoro-meta-sulfonate esterification and benzyl group protection using thio-galactoside 224 as the starting material. Following the SN2 reaction and trifluoro-meta-sulfonate esterification, tetrabutyl ammonium azide was used to make the azide intermediate 228. The C2 ester was then hydrolyzed and methylated to produce the galactoside derivative 230. Following the debenzylation of the protected group, acetylation, click, and bromination reactions, the -bromogalactose derivative 233 was made, and the target compound 235 was made following the glycosylation process, click reaction, and removal of the protective group.
Fig.1 Synthesis of tetrahydropyran galactose derivatives. (Yong, et al., 2022)
A new tetrahydropyran-based scaffold was found as a result of efforts to find thio-disaccharide mimics with fewer H-bond donors to enhance permeability and bioavailability. By removing hydroxyl groups not needed for hydrogen bonding to the hGal-3 CRD, the number of H-bond donors was decreased. Research shows that the monosaccharide molecule that binds at subsite D in the hGal-3 CRD may be replaced by an appropriately functionalized tetrahydropyran ring and that this may be a suitable scaffold for future development and assessment.
CD BioGlyco has an advanced Synthesis Platform to provide customized service in the synthesis of tetrahydropyran-based thio-disaccharide mimics according to research needs. If you are interested in our services, please feel free to contact us for more detailed information.
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