<jats:title>Abstract</jats:title><jats:p>The crude petroleum‐ether extract of the aerial parts of <jats:italic>Hypericum calycinum</jats:italic> L. (Guttiferae) exhibited <jats:italic>in vitro</jats:italic> growth‐inhibitory activity against the Co‐115 human colon carcinoma cell line. Bioassay‐guided fractionation of this extract allowed the isolation of the cyclohexadienone derivatives <jats:bold>1–5</jats:bold>, four of which are previously undescribed compounds. The structures of the known chinesin <jats:bold>II (1)</jats:bold> and of <jats:bold>2</jats:bold> (hypercalin A) were established by <jats:sup>1</jats:sup>H‐ and <jats:sup>13</jats:sup>C‐NMR spectroscopy and were confirmed by X‐ray analysis of their crystalline mixture which revealed the complete relative configuration of both compounds. The structure of <jats:bold>3</jats:bold> (hypercalin B) was elucidated by means of extensive 1D‐ and 2D‐NMR experiments, including DQ‐COSY, HETCOR and LR‐HETCOR. The structure of compound <jats:bold>4</jats:bold> (hypercalin C) was established by <jats:sup>1</jats:sup>H‐ and <jats:sup>13</jats:sup>C‐NMR spectroscopy and confirmed by X‐ray analysis to be the 3,5‐dihydroxy‐4‐{[(1<jats:italic>R</jats:italic>*,2<jats:italic>S</jats:italic>*, 5<jats:italic>S</jats:italic>*)‐2‐hydroxy‐2‐methyl‐5‐(1‐methylethenyl)cyclopentyl]methyl}‐6,6‐bis‐(3‐methylbut‐2‐enyl)‐2‐(2‐methylpropanoyl)cyclohexa‐2,4‐dien‐1‐one. The structures of the higher isomeric homologues <jats:bold>5a/5b</jats:bold> were deduced by comparison of their UV, <jats:sup>1</jats:sup>H‐, and <jats:sup>13</jats:sup>C‐NMR spectra with those of <jats:bold>4</jats:bold>. The isolated compounds appeared to be related to chinesin <jats:bold>I</jats:bold> and <jats:bold>II</jats:bold> previously isolated from <jats:italic>Hypericum chinense</jats:italic> L. and were responsible <jats:bold>for</jats:bold> the growth‐inhibitory activity of the extract against the Co‐115 human carcinoma cell line. Moreover, <jats:bold>1/2</jats:bold> and <jats:bold>3</jats:bold> showed molluscicidal activity against the schistosomiasis‐transmitting snail <jats:italic>Biomphalaria glabrata</jats:italic>.