I have just re-read your initial inquiry of 21.07.98 and found that you
simply need to incorporate d-allo-Thr into peptide chain during Fmoc-SPPS
and that Fmoc-allo-thr(t-Bu)OH is not actually your final objective. Then,
depending on the peptide length and allo-thr position you should choose one
of the much easier solutions to your problem:
1. You could quite safely couple Fmoc-allo-thr-OH as such = without any
side chain protection;
2. Alternatively, you can quite easily synthesize Fmoc-allo-thr(Trt)-OH ;
All references and some details concerning these two approaches you will
find
in NovaBiochem 97/98 Catalog, pp. S31; S64-S65. Perhaps this very useful
up-to-date Peptide Synthesis Handbook is worth a special award from ABRF...
Good luck!
Igor
<rodionov@fibkh.serpukhov.su>
==================================================
Letter of 21.07.98
I'm going to carry out a SPPS where Fmoc-D-allo-Thr-OH is involved.
I need to protect the hydroxy side chain with tBut, leaving the COOH
free.
Could anyone suggest me a procedure to do that?
Thanks very much
Luca Corte
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Letter of 22.07.98
Hi everybody!
Thanks to mr Wolfe for the reply regarding Thr protection, but I think
I have not been clear in my question: I already have Fmoc-d-allo-Thr-OH, so
I
would like to do the side chain OH protection without affecting the
COOH and leaving the Fmoc group intact.
I thought to block the carboxy function as a methyl ester with
diazometane, then protect the side chain OH with TBTA and BF3.Et2O,
then remove the methyl ester with 2% Na2CO3 in H2O/ACN (this
procedure is similarly described in J. Org. Chem., 1991, 56, 3447 for
Fmoc-Tyr).
I don't know if the protection with diazomethane will affect only the
COOH or the side chain OH, too.
Any suggestion, or any other protection procedure is welcomed.
Thanks very much.
Luca
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Letter of 06.08.98
Hallo everybody.
Is there someone out there who can help me?
I'm trying to protect the OH side chain of Fmoc-Thr-OMe with tBu,
using TBTA (tert-butyl 2,2,2,trichloroacetimidate),
catalyzed by BF3.Et2O, following the paper by Armstrong et al.,
(1988) Tetrahedron lett., 29, 2483.
It seems to be a quick and efficient procedure, but my results are
very poor. In fact, only a small part of Thr has been protected the
other won't react. If I add some other TBTA, it soon degrades to
trichloroacetamide, which precipitates as it is not soluble in the
reaction solvent, cyclohexane. I don't know why TBTA decomposes so
quick, the bottle is new, but it seems that even BF3 tends to
destroy TBTA (I tried to mix the 2 together before adding them to the
aa solution, and after some seconds, I got a white precipitate). As I
don't know exactly the reaction mechanism, I don't know where I am going
wrong. So, if someone has already tried tBut protection this way, I
hope he/she will be able to answer me.
Thanks very much
Luca Corte
Biostrands
Area Science Park
Trieste, Italy