Sunday, December 04, 2005

diketopiperazine synthesis found

After a bit of digging, I found a published synthesis for a library of diketopiperazines with the same substitution pattern as in our anti-malaria candidates. My initial guess was pretty close and the published synthesis answered some of my concerns.
1) They do use a reductive amination step but not at the last step to avoid having to do the cyclization with a secondary amine.
2) The cyclization is not used to cleave from the solid support. Instead the dipeptide is freed then cyclized in refluxing toluene.

Details can be found on page 571 of this review article. The original article is here Gordon, D.W. and Steele,J. Biomed. Chem. Lett. 1995, 5, p. 47.

Next step on this project: Find a commercial source for the 2 boc protected amino acids, the aldehyde, the resin and necessary reagents. Place each one in the molecule blog.

3 Comments:

At 9:39 AM, Anonymous nbk2000 said...

When liquid aspartame (Nutra-Sweet)is stored in temperatures above 85
degrees Fahrenheit, it breaks down into diketopiperazine (DKP)and formaldehyde.

 
At 11:56 AM, Blogger Jean-Claude Bradley said...

I would expect methanol to be liberated, not formaldehyde. An amide is formed as the ester is cleaved.

 
At 12:58 PM, Anonymous nbk2000 said...

Apparently it's DKP and methanol, which then gets converted into formaldehyde in the body.

Interesting video (about an hour long) about the health effects of Nutra-Sweet:

http://www.google.com/search?q=sweet.misery

 

Post a Comment

Links to this post:

Create a Link

<< Home

Creative Commons Attribution Share-Alike 2.5 License