Together with various teammates (MSc students) we worked on the hit-lead optimisation of Tagitinin C - a toxic germanocrolide inhibiting the ubiquitin-proteasome pathway.
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The molecule was notoriously sensitive to acids, bases, nucleophiles, and UV light. Resources were limited, and we were performing multi-step syntheses on just 𝟱 𝗺𝗴 𝘀𝗰𝗮𝗹𝗲𝘀, in 𝘁𝗶𝗻𝘆 𝗿𝗼𝘂𝗻𝗱-𝗯𝗼𝘁𝘁𝗼𝗺 𝗳𝗹𝗮𝘀𝗸𝘀, working in darkened fume hoods.
Over three years, we synthesised dozens of Taginitin C analogues, eventually streamlining the synthesis from 10 to 6 steps 𝘷𝘪𝘢 judicious protection/deprotection strategies.
As an engineer at heart, I wondered how we would scale up if we found a non-toxic, bioactive analogue. That led us to 𝗯𝗶𝗼𝗰𝗮𝘁𝗮𝗹𝘆𝘀𝗶𝘀 (think immobilised enzymes) - screening lipases and esterases to reach, in 1 step, a key intermediate: Taginitol C. This work was patented.
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Europe PMC https://europepmc.org/article/PAT/FR2941697
Google Patents
https://patents.google.com/patent/FR2941697A1/en