Methyl.Magic
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L-Proline Esterification
Does anybody have a good method to transform the L-proline into iits methyl or ethyl ester ?
structure of L-proline :
http://www.bmrb.wisc.edu/metabolomics/standards/L_proline/li...
Thanx in advance !
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Nicodem
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There are quite some methods described in the literature already. Is there a particular reason why you don't use one of those?
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Sauron
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Go see my thread making the following books available for free download
Principle of Peptide Synthesis
The Practice of Peptide Synthesis
You should find your answer in one of those
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Klute
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What do you plan on doing with it? Or is it for the sake of the reaction?
Proline can be used as an efficient aldol catalyst..
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Sauron
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It occured to me that as a newbie you may not have the pw for References yet.
So here is Chapter 2 from The Practice of Peptide Synthesis, with plenty of examples of esterification procedures for a variety of amino acids.
With my compliments.
If you want a specific procedure for methyl or ethyl esterification of proline I suggest you search in JBC (that is Journal of Biological Chemistry)
which is free online - you can have the articles for free once you locate them.
The oldest but still one of the best esterification methods is to suspend your AA in methanol or ethanol (absolute of course) and slowly bubble dry
HCl gas through with stirring. (The Fischer method.) The pages from Bodanzsky's book will give you examples of how to work up.
I looked for any proline-specific published procedure for the Me or Et esters in JBC or the ACS journals but did not see any obvious emtries. However,
I think any of the normal methods ought to suffice.
Fischer method; tosyl chloride for catalust; prep of the acid chloride then rxn with alcohol. For the latter I recommend TCT (cyanuric chloride) in
acetone with TEA for acid scavenger. You need not isolate the acid chloride, you can react with your alcohol in situ.
Aldrich sells the methyl ester hydrochloride so you can obtain physical constants and registry numbers there.
Considering that proline is just pyrollidine-2-carboxylic acid, I would not expect any difficulty in just about any method of esterification you want
to employ. Choose one that is quantitative and easy to work up from afterwards.
[Edited on 22-8-2007 by Sauron]
Attachment: Pages from practiceofpeptidesynthesis.pdf (756kB)
This file has been downloaded 9117 times
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Sauron
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FINALLY found direct examples of preparation of L-proline methyl ester and other esters - see attachment.
[Edited on 22-8-2007 by Sauron]
Attachment: Synthesis of tripeptides containing L-proline, L-hydroxyproline, and glycine .pdf (354kB)
This file has been downloaded 2516 times
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Methyl.Magic
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hey
thank you very much sauron !
85% of the hydrochlorid is acceptable.
Yes, the fisher synthesis of amino-ester is very easy but I dont have a lot of L-proline (only 3g) and I search some pratical experience. I remember
when I was trying to synth tryptophan methyl ester with methanol wich contains some H2O and this water fails my esterification and detroyed the
tryptophan, next I esterified it with TMP but I never isolated it.
_______________________________________
Yesterday I started L-proline estérification.
1,5g of L-proline was dissolved in ~30ml of anhydrous ethanol.
The Hydrogen chloride was generated by dropping conc. HCl solution into 98% sulfuric acid magnetically stirred.
The gas passed through a glasspipe and bubbled in the ethanol/proline suspension.
Today I evaporated the ethanol under vacuum as much as possible. I got a light brown solution. I added 50ml of ether and the L-proline ethyl ester
hydrochloride was precipitated as white powder.
I basified the solution with 5% NaOH and extracted 3 times with 10ml Et2O, washed ether with 5% NaOH until the water layer was clean.
Actually the ether solution is drying with anhydrous MgSO4 during all the night.
The L-proline ethyl ester must be anhydrous ! This week I 'm going to attack it with Phenylmagnesium bromid to synth diphenylprolinol, a long-life
psychostimulant similar to desoxypipradol.
bye
[Edite le 23-8-2007 par Methyl.Magic]
[Edite le 24-8-2007 par Methyl.Magic]
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solo
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Reference Information
desoxypipradol information
This is a request for anyone who works for, or knows someone who works for Ciba Geigy or perhaps someone in an academic setting who can request data
to try and find out why desoxypipradrol was dropped by Ciba Geigy Pharma following human trials in 1958-9
The historywas that Merrell now part of Aventis patented 1952 or thereabouts and ran with pipradrol, which was rather successfull.
Ciba Geigy held the patent for desoxypipradrol and given the success of piradrol they initiated trials, these trials went as far as human trials and
even came up with 1 and 2 mg tablet formulations. then the trials were then stopped and the product never made it to market.
Schering also carried out trials of various diphenylmethylpiperidines which were substituted with hydroxy groups on the piperidine ring and some with
hydroxyethyl group on the nitrogen,none of these made it to market either.
the isomeric 4-(diphenylmethyl)piperidine (desoxypiradrol with the diphenyl methyl group moved opposite the nitrogen) has potent toxic effects on the
islet cells in the pancreas, apparently the 2-(diphenylmethyl)piperidine (desoxypipradrol) does not have these effects so I don't thnk this is the
reason.
perhaps the long duration of action or idiosyncratic reactions were the reason?
In the interests of harm reduction it would be nice to know what they discovered 40 years ago hence this request.
I'm no guinea pig but I am rather interested in desoxypipradrol.
forewarned is forearmed
V.......from bluelight,
http://www.bluelight.ru/vb/showthread.php?t=292451
[Edited on 23-8-2007 by solo]
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Methyl.Magic
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the ether has been distilled to give 1.01g of ethyl prolinate as yellow oil. i didnt distill this oil (i have only 1ml...)
Poor yield = 53% .
For the next extraction, I'll isolate the hydrochloride before transforming it into freebase.
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Sauron
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My best guess is that the relatively poor yield (53 vs 85%) is due to some moisture entrainment in the HCl. If you used bottled HCl instead, or if you
pass your generated HCl through a couple drying bottles of P2O45 or Drierite before admitting it to your perfectly dry methanolic soln, you will
probably up the yield.
Best wat to ensure your methanol is bone dry is to buy the best grade you can get then dry it over a little Na metal and distill it directly into your
reaction vessel, protecting the system with a drying tube of course.
L-proline isn't so costly. Acros sells 100 6 for <$50 US. (Aldrich wants $200.) Acros also sells the methyl ester, but it is $50 for 5 g. So buy
the amino acid and bubble away to your heart's content. If you get your yield up you should get close to 100 g of ester hydrochloride for your $50
investment.
Acros is part f the Thermo-Fisher conglomerate. VWR resells their products in USA and will sell to individuals (whereas most chemical companies will
only deal with corporations or institutions.)
Contact details
VWR International, Inc.
Goshen Parkway 1310, P.O. Box 2656
West Chester, PA 19380-0906
VWR International, Inc.
tel: +1-800-932-5000
http:// www.vwr.com
Another possible cause of the low yield is if you did not adequately treat the AA with HCl gas. You may notice that the Russian workers treat their
proline twice. Treat, remove solvent, add fresh solvent, and treat again.
[Edited on 25-8-2007 by Sauron]
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Maja
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It's even cheaper here :
http://cgi.ebay.com/Source-Naturals-L-Proline-Powder-4oz-Fre...
But don't know about the purity!
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