Conjugation of bile esters to cellulose by olefin cross-metathesis: A strategy for accessing complex polysaccharide structures. (1st October 2019)

• Record Type: Journal Article
• Authors: Dong, Yifan; Novo, Diana C.; Mosquera-Giraldo, Laura I.; Taylor, Lynne S.; Edgar, Kevin J.
• Is Part Of: Carbohydrate polymers. Volume 221(2019)
• Page Start: 37
• Page End: 47
• Publication Date: 2019-10-01
• Subjects: Cellulose -- Bile salt -- Cross-metathesis -- Oral drug-delivery -- Amorphous solid dispersion -- Bioavailability; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2019.05.061
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: Cross-metathesis of modified bile acids with cellulose ω-unsaturated ethers. Selectively append complex, multifunctional moieties to polysaccharides. Insight into synergistic drug-crystallization inhibitor solubility and nucleation. Abstract: Bile salts tend to form micelles in aqueous media and can thereby contribute to drug solubilization; they also exhibit crystallization inhibition properties that can stabilize supersaturated drug solutions. Herein, we explore conjugation of bile salts with polysaccharides to create new, amphiphilic polysaccharide derivatives with intriguing properties, portending broad utility in various applications. We introduce efficient conjugation of cholesterol (as a model steroid), lithocholic acid, and deoxycholic acid by mild, modular olefin cross-metathesis reactions. These small molecules were first modified with an acrylate group from the A-ring hydroxyl, then reacted with cellulose derivatives bearing olefin-terminated metathesis "handles". Successful conjugation of bile acids has demonstrated chemoselective cross-metathesis with complex, polyfunctional structures, and large multi-ring systems. It also enabled an efficient, general pathway for polysaccharide-bile salt conjugates, which promise synergy for applications such as amorphous solid dispersion (ASD).