Sunday, November 04, 2007

CombiUgi Update: the Master Table

It has been a while since my last update on the CombiUgi project. Those who have been following the UsefulChem wiki and mailing list will be aware of all the experiments and discussions but it helps to take a look at the big picture periodically.

My last post described our new focus on trying to make falcipain-2 inhibitors and Rajarshi was kind enough to do some docking runs for us. To keep costs low, we started using a library of Ugi products that we can make just from starting materials that we have in abundance (at least 5 g) in our lab.

Four undergraduate students have joined the group in the past few weeks and have been trained to perform the Ugi reaction in 1 dram vials. We initially started doing these in 1.5 ml Eppendorf tubes but they didn't seal perfectly with methanol and leaked during vortexing.

We are currently focusing on Ugi products which precipitate within a few days from the reaction mixture. We were very fortunate in that our first Ugi products crystallized from methanol. It turns out that not all Ugi products behave that way but we are hoping that enough will from the first few hundred falcipain-2 hits to have a handful of compounds to test.

Those reactions that generate pure products as precipitates are tremendously easier to run and scale up compared to requiring a chromatography purification step. If we can provide a list of Ugi products that can be easily prepared this way, I think that would be useful for other researchers with other applications in mind. Maybe we will identify patterns in different solvents that will enable us to understand (or at least empirically predict) how to induce precipitation for a given Ugi product. This kind of practical laboratory advice would add to the knowledge base of information on the Ugi reaction provided in a recent Nature Protocol report by Stefano Marcaccini and Tomás Torroba. (unfortunately not Open Access)

To keep track of all of this, results are pooled in a GoogleDoc Master Table on the CombiUgi page. Look on the experiment number to locate the experimental details from the experiment list page.

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