Filicinic Acid-Based\nMeroterpenoids with Antiproliferative\nActivity against Prostate Cancer PC‑3 Cells from <i>Dryopteris\nwallichiana</i>

Nine new structurally diverse filicinic acid–based\nmeroterpenoids\n(<b>1</b>–<b>9</b>) with four kinds of carbon skeletons\nwere isolated from the rhizomes of Dryopteris wallichiana. Their structures, including the absolute configurations, were elucidated\nby comprehensive analysis of spectroscopic data, quantum chemical\ncalculations, and single-crystal X-ray diffraction. Structurally,\ncompounds <b>1</b>–<b>4</b> feature an unprecedented\n6/6/5/6/6/6 hexacyclic system with a rare oxaspiro[4.5]decane core\nlinking the filicinic acid and <i>ent</i>-kaurane-type diterpene\nmoieties. Compounds <b>5</b>–<b>6</b> are rare\nhybrids of filicinic acid and carotane-type sesquiterpene. Compound <b>7</b> is an unusual rearranged filicinic acid-carotane-type sesquiterpene\nmeroterpenoid. Compounds <b>8</b>–<b>9</b> are\ntwo enantiomeric pairs of new meroterpenoids constructed by filicinic\nacid and a germarane-type sesquiterpene. A plausible biosynthetic\npathway for the nine compounds was proposed. Notably, compounds <b>5</b>, <b>6</b>, (+)/(−)-<b>8</b>, and (+)/(−)-<b>9</b> were discovered to possess antiproliferative activity against\nPC-3 cells based on virtual screening, and in vitro bioassay. An interactive\npreprint version of the article can be found at https://www.authorea.com/doi/full/10.22541/au.172666991.17272585/v1.