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Synthesis of Cyclohexapeptides Containing Pro and Aib Residues
Author(s) -
Jeremic Tatjana,
Linden Anthony,
Heimgartner Heinz
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490275
Subject(s) - chemistry , hexafluorophosphate , yield (engineering) , reagent , cyclic peptide , stereochemistry , proline , glycine , amino acid , aminoisobutyric acid , ring (chemistry) , peptide , organic chemistry , catalysis , biochemistry , ionic liquid , materials science , metallurgy
Cyclization reactions on hexapeptides containing several α ‐aminoisobutyric acid (=2‐amino‐2‐methylpropanoic acid; Aib) residues and the turn‐promoting glycine (Gly) and proline (Pro) residues were investigated. Eight linear hexapeptides were synthesized, and their cyclization was attempted with various coupling reagents. The macrolactamization step proved to be difficult since only three hexapeptides could be cyclized. Two of these latter peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Aib‐Aib‐Phe‐Pro‐Aib‐Gly) ( 1 ). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site by using DEPBT as the coupling reagent, whereas the cyclization at the Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively (DEPBT=3‐[(diethoxyphosphoryl)oxy]‐1,2,3‐benzotriazin‐4(3 H )‐one, PyAOP=(1 H ‐7‐azabenzotriazol‐1‐yloxy)tripyrrolidin‐1‐ylphosphonium hexafluorophosphate, DEPC=diethyl phosphorocyanidate). Another cyclic hexapeptide, cyclo(Aib‐Aib‐Gly‐Aib‐Pro‐Gly) ( 2 ) was prepared in 34% yield when DEPC was used in the cyclization step. The solid‐state conformation of 1 was established by X‐ray crystallography.