Total synthesis of a reversed cyclopurpuracin using a combination of solid and solution phase methods

Cyclopurpuracin is a cyclooctapeptide isolated from the methanol extract of Annona purpurea seeds with the following sequence cyclo-Gly-Phe-Ile-Gly-Ser-Pro-Val-Pro residue. In this study, a reversed cyclopurpuracin, namely cyclo-Pro-Val-Pro-Ser-Gly-Ile-Phe-Gly, was successfully synthesized using a combination of solid and solution phase synthesis methods. The precursor was head-to-tail cyclized using 1.25 mM in DCM with 3 eq. HBTU and 1% v/v DIPEA. The final product was obtained (3.8 mg) with an overall yield of 7.4%. The synthetic products were characterized by HR-ToF-MS, H-1-NMR, C-13-NMR, and 2D NMR, showing different NMR profiles. The presence of the conformation was confirmed by providing additional signals in the H-1 NMR and C-13 NMR spectrum and the correlation peaks shown by 2D NMR. The presence of the cis conformer in conformer B was proven by the chemical shifts of Ser(6) C beta, Pro(7) C beta, and Pro(8) C beta in conformer B, which were more upfield than the conformer A chemical shifts, and the presence of NOE correlation between H alpha/H alpha of Val(7) and Pro(8). The NMR of the reversed cyclopurpuracin revealed the presence of two conformers, conformer A (cyclo-[trans-Pro-Val-trans-Pro-Ser-Gly-Ile-Phe-Gly]) and conformer B (cyclo-[cis-Pro-Val-trans-Pro-Ser-Gly-Ile-Phe-Gly]). The presence of dual conformers has not been observed in the NMR spectra of natural cyclopurpuracin.

Automated summary

Cyclopurpuracin, a cyclooctapeptide, was synthesized in reverse, and its characterization revealed the presence of dual conformers. This study contributes to a better understanding of the structure and properties of Cyclopurpuracin.