Total Synthesis of the Neurotoxic Natural Product Tetrodotoxin with Dr. David Konrad

[@science_and_anonymous]

This is one of those episodes that took my breath away, what incredible chemistry. This man deserves his Ph.D. and then some, what amazing work.

[@fredgrinfeld4921]

I had the pleasure of being one of Trauner's students in undergrad at NYU--though I was one lousy orgo student! Well done, Dr. Konrad!

[@annunzarizzle]

How did they figure out the cosolvent ratios for the ketohydroxylation

[@Tienous_08]

Screening and optimizations most probably

[@annunzarizzle]

@@Tienous_08 well yes but i mean more where do you start with that type of thing was it hts or manual, was there precedence or do you just yolo since the yield is low. What's the rationale for adding the specific cosolvents and to follow that what's the rationale for the resulting ratios?

[@mememachine2586]

awesome presentation!

[@童乙]

I'm confused how simply installing the Ms group to the -OH group would result in elimination at that position affording an alkene?

[@FatalFistFury]

Someone else can correct me if I'm wrong but, Methanesulfonyl chloride (MsCl) was chosen in order to set the stage for an E2 reaction. Additionally, having a nitro group (NO2) allow the protons on the carbon adjacent to the nitro group to be acidic (I don't know the approximate pKa of these protons). This allowed for the easy E2 reaction to occur. In my opinion, it is a testament to the author's highly insightful chemical intuition and rigorous experimental planning. It may also be that they were lucky, but given the monumental achievement of the synthesis, I would go with the former reasons.

[@BeakerBreaker77]

Excellent