18 research outputs found
Computational Analysis of the Potential Energy Surfaces of Glycerol in the Gas and Aqueous Phases:Â Effects of Level of Theory, Basis Set, and Solvation on Strongly Intramolecularly Hydrogen-Bonded Systems
Synthesis of Quinone Methide Precursors for the Treatment of Organophosphorus Poisoning
Eighteen quinone methide precursors (QMPs) were synthesized to test their efficacy at resurrecting organophosphorus-aged acetylcholinesterase. This library of QMPs is based on a phenol framework, and the alkyl groups were chosen based on promising results from similar QMP libraries. The QMPs were synthesized via two methods. The quinone methide precursors with a cyclic R’ group were synthesized via a Suzuki Coupling reaction. The QMPs with conjugated R’ groups were synthesized via a Wittig reaction. Both synthetic pathways ended with a Mannich reaction which installed one of five different aminomethyl groups
2,3-Anhydrosugars in Glycoside Bond Synthesis. NMR and Computational Investigations into the Mechanism of Glycosylations with 2,3-Anhydrofuranosyl Glycosyl Sulfoxides
2,3-Anhydro Sugars in Glycoside Bond Synthesis. Highly Stereoselective Syntheses of Oligosaccharides Containing α- and β-Arabinofuranosyl Linkages
Synthesis of oligosaccharide fragments of mannosylated lipoarabinomannan appropriately functionalized for neoglycoconjugate preparation.
Study of <i>para</i>-Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase
Acetylcholinesterase
(AChE) is an essential enzyme that can be
targeted by organophosphorus (OP) compounds, including nerve agents.
Following exposure to OPs, AChE becomes phosphylated (inhibited) and
undergoes a subsequent aging process where the OP–AChE adduct
is dealkylated. The aged AChE is unable to hydrolyze acetylcholine,
resulting in accumulation of the neurotransmitter in the central nervous
system (CNS) and elsewhere. Current therapeutics are only capable
of reactivating inhibited AChE. There are no known therapeutic agents
to reverse the aging process or treat aged AChE. Quinone methides
(QMs) have been shown to alkylate phosphates under physiological conditions.
In this study, a small library of novel quinone methide precursors
(QMPs) has been synthesized and examined as potential alkylating agents
against model nucleophiles, including a model phosphonate. Computational
studies have been performed to evaluate the affinity of QMPs for the
aged AChE active site, and preliminary testing with electric eel AChE
has been performed