Khan
5
|
of peptide synthesis protocol through the coupling of the Boc-
Gly-OH and H2N-Gly-OH. A 2 + 2 DCC-HOBt (hydroxy
benzotriazole)-mediated coupling[30,31] of the H2N-Phe-
Met-OBzl and Boc-Gly-Gly-OH yielded the tetrapeptide, Boc-
Gly-Gly-Phe-Met-OBzl, which was deprotected to free amine
using 5N HCl-dioxane followed by resulting hydrochloride salt
neutralization with N-methyl morpholine (NMM) and con-
densing the obtained free amine to Boc-Tyr-OH, again mediat-
ed by DCC-HOBt, at cooled conditions. The Boc-Tyr-OH was
prepared from Boc-Tyr-OMe, which itself was obtained from
HCl.H2N-Tyr-OMe starting from the L-Tyr amino acid. The
protected pentapeptide sequence, Boc-Tyr-Gly-Gly-Phe-Met-
OBzl, was hydrogenated for 20 min over 10% Pd-C with for-
mic acid in a transfer hydrogenation step.[32–34] The obtained
formate salt, a highly hygroscopic product, was converted
to HCl.Tyr-Gly-Gly-Phe-Met-OH by 5N HCl-dioxane treat-
ment in the presence of thioanisole and mercaptoethanol. The
hydrochloride salt was neutralized, worked up, and recrystal-
lized to give the desired pentapeptide sequence, H2N-Tyr-Gly-
Gly-Phe-Met-OH, in 66% yields with its identity confirmed
through comparison with an in-house reference standard and
spectro-analytical techniques. Thus, the desired pentapeptide
was synthesized in a stepwise and linear elongation of the pep-
tide chain starting from C-terminus (Scheme 1) in a 2 + 2 + 1
fragments convergent approach.
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4
CONCLUSION
|
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The current approach in protection and deprotection strategy
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CONFLICT OF INTEREST
There is no conflict of interest.
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