Institution: | 1. Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia;2. Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia
Study Center of Natural products and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia;3. Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia
Laboratorium Sentral, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia
Study Center of Natural products and Synthesis, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Kabupaten Sumedang, Indonesia |
Abstract: | Xylapeptide A is a cyclopentapeptide, cyclo-D-Ala-L-Val-N-Me-L-Phe-L-Pip-L-Leu], first isolated from Xylaria sp. × Sophora tonkinensis, together with its analogue, xylapeptide B, which differ by only one residue, proline in xylapeptide B is replaced by pipecolinic acid (Pip) in xylapeptide A. Both xylapeptides A and B possess antimicrobial properties against several bacteria and fungi. Herein, we describe the first total synthesis and antimicrobial evaluation of xylapeptide A containing two non-proteinogenic residues, N-Me-phenylalanine and pipecolinic acid. The synthesis of xylapeptide A was achieved by a combination of solid- and solution-phase methods that were applied for the synthesis of xylapeptide B. Interestingly, the cyclization of linear xylapeptide A was more straightforward yielding 22% compared to 8.9% for xylapeptide B, suggesting that the presence of pipecolinic acid in the linear precursor affected the cyclization process. NMR analysis of synthetic xylapeptide A revealed that the chemical shifts of all protons and carbons of xylapeptide A are highly similar to the natural product. The synthetic xylapeptide A, together with xylapeptide B, were evaluated for their antimicrobial properties, showing that synthetic xylapeptide A has moderate antimicrobial activity and better antimicrobial properties compared to synthetic xylapeptide B. The presence of pipecolinic acid in xylapeptide A is an important requirement for antimicrobial activity. |