A synthetic approach to tetrodotoxin : via oxidative amidation of a phenol

This dissertation describes synthetic efforts towards tetrodotoxin. Contact with tetrodotoxin brings upon paralytic shellfish poisoning (PSP) for the unfortunate victim. The syndrome can be fatal in extreme cases and symptoms include nausea, numbing of the lips and body, throat constriction, slurred speech, and loss of coordination. Our approach stems from the oxidative amidation of a phenol as a key step. This technology installs a necessary nitrogen-functionality of the natural product at an early stage; ultimately the route was optimized to allow the synthesis to proceed in a practical manner.Science, Faculty ofChemistry, Department ofGraduat

The Chemical Synthesis of Tetrodoxin : An Ongoing Quest

This contribution reviews all the synthetic work on tetrodotoxin that has appeared in the literature through June 2011.Science, Faculty ofChemistry, Department ofReviewedFacult

Assembly of a Key Dienic Intermediate for Tetrodotoxin via a Machetti–DeSarlo Reaction

A route to a racemic diene intermediate for the synthesis of tetrodotoxin is described. Key steps of the sequence leading to such a compound include the oxidative amidation of a phenol, a Cu­(II)-catalyzed cyclocondensation of a nitroketone with an olefin (Machetti–DeSarlo reaction), and a nucleophilic fragmentation of the resulting isoxazoline. Several unusual reactions encountered in the course of this study are thoroughly discussed

Intraocular Inflammation Incidence Following Intravitreal Brolucizumab Injection for Exudative Age-Related Macular Degeneration

PURPOSEWe evaluated the clinical outcomes of Intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODSA retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021 were reviewed. RESULTSThere were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline logMAR best-corrected visual acuity (BCVA) was 0.32 0.2 (20/42), while it was 0.580.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There were no known case of retinal vasculitis. Management of IOI included topical steroids in 7 eyes (54%), topical and systemic steroids in 5 eyes (38%), and observation in one eye (8%). BCVA returned to baseline and inflammation resolved in all eyes by last follow-up examination. CONCLUSIONSIntraocular inflammation following brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by last follow-up visit