Wednesday, August 30, 2006

Working on the Ugi

Going over some of the other papers that Chris Hulme wrote regarding the Ugi reaction and diketopiperazines, there are a few more answers but a few more questions

1) We now know that he used 1,2-dichloroethane in the 10%TFA solution for cyclization from a review paper
2) In the same review paper, there are some small changes to the procedure that make it safer and less complicated than we originally thought. While it does not specify that it uses MeOH (looks like they used ethyl glyoxalate) in the Ugi reaction it says that it was under reflux over night not just stirring at room temperature.
3) the cyclization step can be done with 10% of AcCl in MeOH (AcCl reacts immediately with methanol to generate anhydrous HCl when prepared separately, as done by Tenderbutton, it would then be added to the mixture) or TFA in 1,2-dichloroethane and it was done at room temp over night
4) the review paper mentioned above looks like it gives HMR info of two diketopiperazines which can be used for comparing NMRs when we are fairly certain we have obtained our product.

Some of the questions that we have brought up now that we have compared some NMRs of Boc-protected amino acids and from reading the paper mentioned above are as follows

1) can we have tautomerization in the cyclized diketopiperazine ring since we have amides? We have observed in our HMR of our Boc protected amino acids (Boc-Gly-OH and N-Methionine) there is some peak splitting which we can interpret to be tautomerization.
2) there are complications using dichloroethane in that it can react with our amine and other amine byproducts so why did Hulme used this particular solvent?
3) since most of Hulme's experiments were automated and purified by HPLC, is the product diketopiperazine difficult to purify by chromatography?

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