Synthesis of a Cyclooctapeptide, Cyclopurpuracin, and Evaluation of Its Antimicrobial Activity.

Cyclopurpuracin is a cyclooctapeptide isolated from the methanol extract of seeds with a sequence of cyclo-Gly-Phe-Ile-Gly-Ser-Pro-Val-Pro. In our previous study, the cyclisation of linear cyclopurpuracin was problematic; however, the reversed version was successfully cyclised even though the NMR spectra revealed the presence of a mixture of conformers. Herein, we report the successful synthesis of cyclopurpuracin using a combination of solid- and solution-phase synthetic methods. Initially, two precursors of cyclopurpuracin were prepared, precursor linear A (NH-Gly-Phe-Ile-Gly-Ser(-Bu)-Pro-Val-Pro-OH) and precursor linear B (NH-Pro-Gly-Phe-Ile-Gly-Ser(-Bu)-Pro-Val-OH, and various coupling reagents and solvents were trialled to achieve successful synthesis. The final product was obtained when precursors A and B were cyclised using the PyBOP/NaCl method, resulting in a cyclic product with overall yields of 3.2% and 3.6%, respectively. The synthetic products were characterised by HR-ToF-MS, H-NMR, and C-NMR, showing similar NMR profiles to the isolated product from nature and no conformer mixture. The antimicrobial activity of cyclopurpuracin was also evaluated for the first time against , , and , showing weak activity with MIC values of 1000 µg/mL for both synthetic products, whereas the reversed cyclopurpuracin was more effective with an MIC of 500 µg/mL.