Accidental nerve transection or injury is a significant morbidity associated with many surgical interventions, resulting in persistent postsurgical numbness, chronic pain, and/or paralysis. Nervesparing can be a difficult task due to patient-to-patient variability and the difficulty of nerve visualization in the operating room. Fluorescence image-guided surgery to aid in the precise visualization of vital nerve structures in real time during surgery could greatly improve patient outcomes. To date, all nerve-specific contrast agents emit in the visible range. Developing a nearinfrared (NIR) nerve-specific fluorophore is poised to be a challenging task, as a NIR fluorophore must have enough "double-bonds" to reach the NIR imaging window, contradicting the requirement that a nerve-specific agent must have a relatively low molecular weight to cross the blood-nerve-barrier (BNB). Herein we report our efforts to investigate the molecular characteristics for the nerve-specific oxazine fluorophores, as well as their structurally analogous rhodamine fluorophores. Specifically, optical properties, physicochemical properties and their in vivo nerve specificity were evaluated herein.
Allyl
2-diazo-2-phenylacetates are shown to react with trimethylsilyl
thioethers in the presence of rhodium(II) catalysts to generate α-allyl-α-thio
silyl esters. The transformation involves a tandem process involving
formal rhodium-catalyzed insertion of the carbene group into the S–Si
bond to generate a silyl ketene acetal, followed by a spontaneous
Ireland–Claisen rearrangement. The silyl ester products were
isolated as the corresponding carboxylic acids after aqueous workup.
Intramolecular cyclopropanation of the allyl fragment generally competes
with addition of the heteroatom to the carbene center. The reaction
occurs under mild conditions and in high yield, allowing for rapid
entry into rearrangement tetrasubstituted products. Propargyl esters
were shown to generate the corresponding α-allenyl products.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.