Journal of Glycomics & Lipidomics
Open Access

Abstract

Glycolipids and glycopeptides: Minimally competent Lewis acid catalysis produces surfactants for use ex vivo and in vivo

Robin Polt

Use of minimally competent main group Lewis acids such as InBr3 and Bi (OSO2CF3)3 permit the formation of glycosides in high yield and purity from simple sugar per-acetates at room temperature or above with remarkable α/β-selectivity. Classical reactions rely on very reactive glycosyl donors in conjunction with metal promoters (Hg++, Ag+ etc). Newer methods have used trichloroacetimidates and strong Bronsted or Lewis acids or thioglycosides in conjunction with oxidative or thiophilic activators. Use of the more stable glycosyl per acetates in conjunction with stoichiometric amounts of strong Lewis acids (BF3.Et2O, FeBr3 etc) has been explored with limited success. The use of “minimally competent” Lewis acids has allowed us to perform glycosidation reactions with catalytic amounts of InBr3 or Bi (OTfl)3 well above room temperature and without significant decomposition of the glycoside products. We will discuss the exploitation of these methods to produce glycolipid surfactants from renewable resources as well as glycopeptide drugs that penetrate the blood-brain barrier (BBB). These “biousian glycopeptides” are not subject to “Lipinski’s rules” that would otherwise eliminate them as CNS drug candidates. Glycosylated amphipathic helices or “address segments” have been used to target G-protein coupled receptors (GPCRs) in the brain after intravenous administration. The addition of glycosides to endogenous peptide neurotransmitters and peptide hormones imparts favorable pharmacokinetic and pharmacodynamics (PK/PD) properties and enables penetration of the BBB which is not constrained by molecular weight.
 

Published Date: 2021-03-16;