Carboxamide protection in peptide synthesis
Abstract
In the first part the use of 4-methoxy-2-
-methylbenzyl and 4-methoxy-l-naphthalenemethyl as
protecting groups for the amide side chain of
glutamine and asparagine during peptide synthesis
is demonstrated. The second part involves the
hydration of some cyano containing model compounds
(cyano group is an undesired functional group
formed ty the dehydration of the unprotected carboxamide
group when N,N"':'dicyclohexylcarbodiimide is used
as the coupling reagent in the course of peptide
synthesis) under mild conditions to the corresponding
carboxamide containing products.
4-Methoxy-2-met-bylbenzonitrile and 4-methoxy-lnaphthonitrile
were reduced to 4-methoxy-2-methylbenzylamine
and 4-methoxy-l-naphthalenemethylamine
respectively using lithium aluminium hydride in ether.
These groups were then used to prepare the carboxamide
CA
protected derivatives viz. Carbobenzoxy-N -4-methoxy-
CA
-2-methylbenzylleucinamide; carbobenzoxyleucyl-N -4-
-methoxy-2-methylbenzylglycinamide; tert-butyloxycarbonylphenylalanyl-
a-benzyl-N CA-4-methoxy-2-methylbenzylasparaginate;
tert-butyloxycarbonylglycyl-
-phenylalanyl-a-benzyl-NCA-4-methOxy-2-methylbenzyl-
-asparaginate; carbobenzoxy-NCA-4-methoxy-l-naphthal-
-enemethylleucinamide; carbobenzoxy-NCA-4-methoxy-l-
naphthalenemethylglycinamide; tert-butyloxycarbonylphenylalanyl-
a-benzyl-N CA -4-methoxy-I-naphthalenemethylasparaginate;
and tert-butyloxycarbonylglycyl-
phenylalanyl-a-benzyl-N CA -4-methoxy-I-naphthalenemethylasparaginate.
Cleavage of all protecting
groups (i.e. Carboxamide, Carboxyl, and Amino) is
carried out using boron trifluoride with acetic acid
complex (B7FA) to obtain the fully deprotected
products i.e. leucinamide; leucylglycinamide;
phenylalanylasparagine and glycylphenylalanylasparagine.
In the second part, model studies on the
hydration of nitrile to the amide using (i) hydrogen
peroxide in a base (Radziszenwskis reaction) and
(ii) 33% hydrogen bromide in glacial acetic acid were
carried out. The nitrile model compounds used for
the study include, benzonitrile; 4-methoxy-l-
-naphthonitrile; carbobenzoxy-S-cyanoalanine;
carbobenzoxy-y-cyano-a-aminobutyric acid; carbobenzoxy-
S-cyanoalanylglycine methyl ester and
carbobenzoxy-y-cyano-a-aminobutylglycine methyl
ester. Carbobenzoxyasparagine and carbobenzoxyglutamine
were dehydrated to their corresponding
cyano derivatives using N,N~-dicyclohexylcarbodiimide
in pyridine at a-~emperature of 16oC. The synthesis
of the cyano dipeptides was carried out using
N-hydroxysuccinimide coupling procedure.
Citation
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University of NairobiPublisher
University of Nairobi Faculty of Sciencem