Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

This study establishes an efficient solid-phase strategy for the total synthesis of segetalins A-H, J and K (<b>1</b>-<b>10</b>), bioactive cyclopeptides isolated from <i>Vaccaria segetalis</i>. Linear precursors were assembled on cost-effective 2-chlorotrityl chloride resin via Fmoc-SPPS, followed by PyBOP-mediated head-to-tail cyclization in DMF (10^-3 M). After RP-HPLC purification, all cyclopeptides were obtained in 45-70% isolated yields. Structural identities were confirmed by HRESIMS, NMR, and HPLC (>95% purity). Circular dichroism (CD) spectroscopy revealed distinct secondary structures, including β-sheets (<b>1</b>, <b>2</b>, <b>3</b>, <b>4</b>, <b>7</b>, <b>8</b>, <b>10</b>) and α-helical elements (<b>5</b>, <b>6</b>). This scalable methodology overcomes limitations of prior syntheses, enabling biological evaluation.