Friday, December 30, 2005

aldehyde problem

It looks like we'll be able to get the amines and BOC-protected amino acids for the Ugi synthesis of the diketopiperazine anti-malaria compounds.

But we have not yet found a commercial source for the aldehyde components so far.
This catechol aldehyde is one of the more common required aldehydes. After looking at several alternatives, the cheapest and most direct route seems to be a pinacol style rearrangement of the amino alcohol adrenaline. Racemic adrenaline is pretty cheap, although the yield is only about 20% in this Korean paper.

These are the concerns I have:

1) The Korean paper reports the heating of perchloric and glacial acetic acids, which I really don't want to do because of the explosive hazard. I am wondering if sulfuric acid will work just as well. The mechanism only involves acid catalysis so I don't see why not.

2) Because the Ugi reaction is carried out in methanol, I am hoping that the phenolic groups will not have to be protected. If they do have to be protected then we'll probably have to make an acetal that will come off during BOC deprotection at the end.

Any comments/ideas/chemicals that would help us?


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