Solution-phase synthesis of Aib-containing cyclic hexapeptides.
The 18-membered Aib-containing cyclohexapeptides, cyclo(-Gly-Aib-Aib-Gly-Aib-Phe-) (22), cyclo(-Gly-Aib-Phe(2Me)-Gly-Aib-Aib-) (24a), cyclo(-Gly-Phe(2Me)-Aib-Gly-Aib-Aib-) (24b), and cyclo(-Gly-Phe(2Me)-Aib-Gly-Aib-Phe-) (25), have efficiently been synthesized by solution-phase techniques. The linear precursors 1a-1d were prepared by combining the 'azirine/oxazolone method' for incorporation of alpha,alpha-disubstituted alpha-amino acids (Aib, Phe(2Me)) into the peptide chains by classical peptide coupling methods for segment condensations. Deprotection of the amino and carboxy termini of 1a-1d, followed by cyclization with DEPC as the coupling reagent, gave the above-mentioned cyclic hexapeptides 22, 24a, 24b, and 25 in good yields (26-57%). The solid-state conformations of the linear hexapeptides 1d, 16 and 27, and of the cyclohexapeptides 22 and 25 have been established by X-ray crystallography.
Jeremic
Tatjana
T
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich.
Linden
Anthony
A
Heimgartner
Heinz
H
D000621:Aminoisobutyric Acids / Q000138:chemical synthesis*; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis*; D012996:Solutions / Q000138:chemical synthesis
D000621:Aminoisobutyric Acids; D009842:Oligopeptides; D012996:Solutions; C100049:2-aminoisobutyric acid