110071-96-0Relevant academic research and scientific papers
A Rapid and Mild Sulfation Strategy Reveals Conformational Preferences in Therapeutically Relevant Sulfated Xylooligosaccharides
Vo, Yen,Schwartz, Brett D.,Onagi, Hideki,Ward, Jas S.,Gardiner, Michael G.,Banwell, Martin G.,Nelms, Keats,Malins, Lara R.
, p. 9830 - 9838 (2021)
Although sulfated xylooligosaccharides are promising therapeutic leads for a multitude of afflictions, the structural complexity and heterogeneity of commercially deployed forms (e. g. Pentosan polysulfate 1) complicates their path to further clinical development. We describe herein the synthesis of the largest homogeneous persulfated xylooligomers prepared to date, comprising up to eight xylose residues, as standards for biological studies. Near quantitative sulfation was accomplished using a remarkably mild and operationally simple protocol which avoids the need for high temperatures and a large excess of the sulfating reagent. Moreover, the sulfated xylooligomer standards so obtained enabled definitive identification of a pyridinium contaminant in a sample of a commercially prepared Pentosan drug and provided significant insights into the conformational preferences of the constituent persulfated monosaccharide residues. As the spatial distribution of sulfates is a key determinant of the binding of sulfated oligosaccharides to endogenous targets, these findings have broad implications for the advancement of Pentosan-based treatments.
A General Approach to O-Sulfation by a Sulfur(VI) Fluoride Exchange Reaction
Ferraro, Samantha L.,Flynn, James P.,Hwang, Seung,Liu, Chao,Niu, Jia,Yang, Cangjie
, p. 18435 - 18441 (2020/08/25)
O-sulfation is an important chemical code widely existing in bioactive molecules, but the scalable and facile synthesis of complex bioactive molecules carrying O-sulfates remains challenging. Reported here is a general approach to O-sulfation by the sulfur(VI) fluoride exchange (SuFEx) reaction between aryl fluorosulfates and silylated hydroxy groups. Efficient sulfate diester formation was achieved through systematic optimization of the electronic properties of aryl fluorosulfates. The versatility of this O-sulfation strategy was demonstrated in the scalable syntheses of a variety of complex molecules carrying sulfate diesters at various positions, including monosaccharides, disaccharides, an amino acid, and a steroid. Selective hydrolytic and hydrogenolytic removal of the aryl masking groups from sulfate diesters yielded the corresponding O-sulfate products in excellent yields. This strategy provides a powerful tool for the synthesis of O-sulfate bioactive compounds.
