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:
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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