Synthesis of thiodisaccharide glycomimetics containing 6-deoxy-furanosyl units

M. LO FIEGO; A.W. HOBSTETER; V. HOLST; G.F. SILBESTRI; C. MARINO; O. VARELA

Congreso; Canadian glycomics symposium; 2019

Gliconet

The interest in galactofuranose-containing molecules arises from the fact that Galf is present in glycoconjugates that are considered to be essential for the survival or virulence of pathogenic microorganisms, but is absent in higher eukaryotes.1 We have synthesized two thioglycomimetics of -D-Galf-(1→5)-D-Galf, a motif present in glycoconjugates of many pathogenic microorganisms. These β-D-thiodisaccharides contain 1-thio-D-galactofuranose as non reducing unit and alternatively 6-deoxy-5-thio derivatives of L-Altf or D-Galf the reducing end. Both thiodisaccharides showed to be competitive inhibitors of the β-D-galactofuranosidase from Penicillium fellutanum.2In this communication is presented the progress towards the synthesis of new thioglycomimetics 3a and 3b. With the aim to achieve the target molecules, the synthesis of the precursor monosaccharides, particularly 5,6-dideoxy-2,3-di-O-acetyl-5-S-acetyl-5-thio-β-D-galactofuranosyl tricholoroacetimidate (1) has been prepared as a versatile glycosyl donor. By condensation of 1 with the glycosylthiol 2a (L-Altf configuration) as acceptor, using TMSOTf as catalyst, 3a, precursor of a new glycomimetic with two sulfur atoms at the reducing end was obtained in 52 %. On the other hand condensation of 1 with 2b (D-Galf configuration) afforded an inseparable mixture of thiodisaccharide 3b and the disulfide formed from two units of 2b. Efforts to improve the condensation and purification of 3b are in course.