Open Source TB

And hopefully we'll be back at it soon, just with a bit of extra PPE 😷 👩‍🔬

We’ve tried THF instead of DMF, + different bases (KOH and NaOH) but our yields are still low..,we think we’re getting the mono-allylated side product, which complicates purification. Any ideas? We’d love suggestions! #ChemTwitter #RealTimeChem #MedChem #OpenSourceTB

#OpenSourceTB's diversity oriented synthesis also includes a double allylation of boc-protected linear polyamine (analogous to the propargylation we mentioned last week). Theoretically, this will help us install other functionalities...

…but we struggled to purify the product of the Michaelis-Arbuzov reaction. We tried a column (DCM:MeOH with 10% NH4) + trituration with toluene, then lockdown interfered. Have you got any ideas for purifying this? We’d love to hear! #ChemTwitter #RealTimeChem #MedChem

Series 4 of #OpenSourceTB has a focus on diversity-oriented synthesis. Here’s one of the routes we planned to install a non-activated alkene. Our first reaction (acylation) had great yields… #MedChem #ChemTwitter #OpenSourceDrugDiscovery #OpenScience

We're struggling to isolate pure product - we think partially bc the reaction mixture contains both mono- and bis-propargylated amine. Read about our attempts (and make suggestions!) here: github.com/KlementineJBS/ELN… Any ideas #ChemTwitter? #RealTimeChem #MedChem #OpenSourceTB

We started trying to use boc-protection to make some bis-functionalised linear polyamines - the plan was to propargylate the protected amine then use a naphthyl-azide coupling partner for a click reaction. #RealTimeChem #OpenSourceTB #ChemTwitter #MedChem #DrugDiscovery

Despite our adventures with cyclam, #OpenSourceTB series 4 is really about the linear polyamine analogues we've been exploring. Our first series of compounds had some promising results but we need to make more to establish some SAR... #DrugDiscovery #Tuberculosis #OpenScience

But the final azidation step remains to be finished (partially due to lockdown, partially due to the product disappearing on a column!) Our first attempt can be found here: github.com/KlementineJBS/ELN… Any suggestions? #RealTimeChem #ChemTwitter #MedChem #OpenSourceTB #DrugDiscovery

We're hoping to use a similar click-coupling reaction, but with a methylazidoferrocene partner. We'd gotten part of the way there...