Forgive me for asking what might be a stupid question, but are you sure
your starting material is Boc-Tyr-OtBu (t-butyl ester of Boc-Tyr) and not
Boc-Tyr(tBu)-OH (t-butyl ether of Boc-Tyr)? I note that Bachem, for
example, sells the latter, but not the former. Otherwise,I don't know why
the esterification should be so difficult. I seem to remember from the dim
past that a standard way to make amino acid p-nitrophenyl esters (which
would be more unstable than your tyrosine ester) was using DCC.
Richard Laursen
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>Hello All,
>
> One possibility, though not likely, is based on the fact that the
>lability of the aryl ester product is much higher than that of a amide
>linkage. I would imagine that aryl esters are more labile than alkyl
>esters which are certainly more labile than amides. In other words,
>perhaps under conditions of the reaction or of the HPLC, it could be that
>the ester is breaking back down to starting materials.
>
> One test of this hypothesis is to try the same activating
>conditions and to couple to an amine instead of tyrosine. Another idea is
>to analyze the reaction by NMR, as opposed to HPLC.
>
> One more thought. Another reagent that some have used to couple
>peptides to amino acids is isobutylchloroformate. I don't know from
>firsthand knowledge that it is any better or worse than your other reagents.
>
>CHris
>
>Original Message appears below:
>-------------------------------------------------------------------------------
>Hello!
>
>We are trying to esterify Boc-Pro to the hydroxyl of Boc-Tyr-OtBu. So
>far all attempts seem to be fruitless. We have tried many kinds of
>COOH activation, from simple DCC to the newest reagents (PyBOP, TFFH,
>uronium salts); we've also added bases (DMAP, DIEA, DBU). By HPLC, all
>reactions show no change from starting materials. What are we doing
>wrong? Could someone point us to useful references in this respect?
>Thank you very much!
>
>--
>David Andreu
>University of Barcelona, Spain
>Phone/Fax: 343-402 1260
>andreu@admin.qo.ub.es
>
>
>
>Christopher Halkides
>Dept. of Chemistry, UNCW
>601 S. College Road
>Wilmington, NC 28403-3297
Richard A. Laursen
Department of Chemistry
Boston University
590 Commonwealth Ave.
Boston, MA 02215
Tel (617) 353-2491; FAX (617) 353-6466
email: <laursen@bu.edu>