New 21- and 24-atom Aib-containing cyclopeptides.
The synthesis of two Aib-containing cyclic octapeptides, cyclo(Leu-Aib-Phe-Aib-Gly-Aib-Phe-Aib) (1) and cyclo(Gly-Aib-Aib-Val-Aib-Leu-Aib-Phe) (2), and a cyclic heptapeptide cyclo(Gly-Aib-Val-Aib-Leu-Aib-Phe) (3), is described. The linear precursors of 1-3 were prepared using solution-phase techniques, and the cyclisation was also accomplished in solution. Among the coupling reagents examined in the final macrolactamisation step, PyAOP, HATU and DEPC/DEPBT efficiently yielded cyclised products. However, the success of the cyclisation was found to be dependent on the coupling reagent used. The two octapeptides 1 and 2 were obtained in much better yields (up to 63%) than the cycloheptapeptide 3 (30-37%). In addition, crystal-state conformational analysis of 2 was performed by X-ray crystallography. Six intramolecular hydrogen bonds stabilise the structure characterised by two consecutive type II'/I beta-turns, two consecutive type II/III' beta-turns, one gamma-turn, and one inverse gamma-turn.
Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, Zürich, Switzerland.
Tatjana
T
Jeremic
Anthony
A
Linden
Heinz
H
Heimgartner
D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*
D000621:Aminoisobutyric Acids; D009842:Oligopeptides; D010456:Peptides, Cyclic