Wednesday, December 21, 2005

Ugi DKP synthesis for malaria

I found a nice little review of diketopiperiazine syntheses. One of the methods involved a one pot solution synthesis (Ugi reaction) with a BOC protected amino acid, an amine and an aldehyde. I have drawn the scheme below in such a way that the R1, R2 and R3 groups are positioned in the same way as in our file of target compounds.

The original article is: The solution phase synthesis of diketopiperazine libraries via the Ugi reaction: Novel application of Armstrong's convertible isonitrile Christopher Hulme*, Matthew M. Morrissette, Francis A. Volz and Christopher J. Burns Tetrahedron Letters
Volume 39, Issue 10 , 5 March 1998, Pages 1113-1116

This should be much simpler and much cheaper than the previous solid phase synthesis I proposed earlier. Since the reaction is carried out in methanol, my guess is that there is no need to protect alcohols in any of the starting materials. Does anyone know if phenols would be a problem in the Ugi reaction?

2 Comments:

At 12:04 PM, Anonymous Anonymous said...

Phenols have similar pKa to carboxylic acids and can react in its stead. I've seen a recent Org. Biomol. Chem. paper describing the use of phenols in the Ugi-three component reaction, albeit with slightly modified conditions.

If you have free phenolic groups in your compounds, it would be best to protect them.

 
At 9:12 AM, Blogger Jean-Claude Bradley said...

Yes phenols can react but it looks like they need electron withdrawing groups, which we don't have so we're going to be bold and try without protection first. More on that here.

 

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