Efficient and Flexible Synthesis of New Photoactivatable Propofol Analogs

Abstract

Propofol is a widely used general anesthetic, which acts by binding to and modulating several neuronal ion channels. We describe the synthesis of photoactivatable propofol analogs functionalized with an alkyne handle for bioorthogonal chemistry. Such tools are useful for detecting and isolating photolabeled proteins. We designed expedient and flexible synthetic routes to three new diazirine-based crosslinkable propofol derivatives, two of which have alkyne handles. As a proof of principle, we show that these compounds activate heterologously expressed Transient Receptor Potential Ankyrin 1 (TRPA1), a key ion channel of the pain pathway, with a similar potency as propofol in fluorescence-based functional assays. This work demonstrates that installation of the crosslinkable and clickable group on a short nonpolar spacer at the para position of propofol does not affect TRPA1 activation, supporting the utility of these chemical tools in identifying and characterizing potentially druggable binding sites in propofolinteracting proteins.

Continuous midazolam infusion can minimize the pro-inflammatory response to anesthesia and surgery for pediatric patients with intra-abdominal infection: Comparative study versus continuous propofol infusion

“…Propofol is an intravenous general anesthetic widely used for general anesthesia and for sedation in ICU [10]. Propofol acts by binding to and modulating several neuronal ion channels and its effects are thought to occur through an impact on the ligand-gated channels including the GABA A receptor [11].…”