mnick12 - 30-1-2013 at 15:16
Hello everyone,
I am interested in synthesizing the some various N-acyl derivatives of L-proline. Right now my interest is in N-phenylacetyl-L-proline ethyl ester or
ethyl 1-(phenylacetyl)pyrrolidine-2-carboxylate. The two most common methods I have run across are the acylation of L-proline with phenylacetyl
chloride, and coupling of proline with phenylacetic acid in the presence of DCC. Both of these methods work quite well but use some expensive or hard
to get reagents.
Recently there have been a few threads regarding the boric acid catalyzed amidation of amines in refluxing toulene. The reaction described in Organic
Syntheses is pretty straight forward, and has good yields. Could a similar type of reaction be used to catalyze the amidation of L-proline ethyl ester
and phenylacetic acid? If so this would negate the use of phenylacetyl chloride and DCC. If not, what would suggest as an alternative for the
acylation of L-proline ethyl ester?
Any ideas are appreciated.
http://www.orgsyn.org/orgsyn/prep.asp?prep=v89p0432
http://deepblue.lib.umich.edu/bitstream/handle/2027.42/41560...
Attachment: US5439930.gsv-111.Noopt.pdf (698kB)
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killer_lapin - 30-1-2013 at 16:50
you can make the methyl ester of proline, then couple your amino acid with your acid ester( not methyl, bigger=better ) which is going to get
displaced by the nitrogene making an amide bond, the you can deprotect your methyl ester on the proline with aqueous lithium hydroxide. The peptidic
bond should resist to this base but not the ester.
you should look for peptide chemistry it's pretty developped but you can still find papers that don't use coupling agent like DCC, HOBT...
mnick12 - 31-1-2013 at 15:25
Are you sure the nitrogen in proline is capable of participating in aminolysis with acceptable yields? If so that would be a good method.
killer_lapin - 31-1-2013 at 16:10
yep pretty sure, i'm doing my undergraduated research in peptidomimetic!
Here is a simple protocole reproducible in a home lab: http://www.orgsyn.org/orgsyn/prep.asp?prep=v88p0042
Removed the colon problem.
[Edited on 4-2-2013 by ScienceSquirrel]
chemrox - 3-2-2013 at 07:58
Hey killer, when place the colon before the http it leads to a lot of irrelevant crap. Just thought you should know and take care. Thanks for the
ref!
mnick12 - 4-2-2013 at 10:25
Thanks for the ref,
I hope I have some time to try this out in the next few weeks.
suewill - 6-2-2013 at 21:04
thanks for the reply