Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived <em>Penicillium purpurogenum</em> G59

Abstract

Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (<strong>1</strong>) and purpurogemutantidin (<strong>2</strong>), and the known macrophorin A (<strong>3</strong>) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived <em>Penicillium purpurogenum</em> G59. Structures and absolute configurations of <strong>1</strong> and <strong>2</strong> were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for <strong>1</strong>–<strong>3</strong> were also proposed and discussed. Compounds <strong>1</strong> and <strong>2</strong> significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound <strong>3</strong> also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce <strong>1</strong>–<strong>3</strong>, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for <strong>1</strong>–<strong>3</strong> production.

Keywords

• purpurogemutantin
• purpurogemutantidin
• sesquiterpene
• meroterpenoid
• structure determination
• antitumor activity
• &lt;em&gt;Penicillium purpurogenum&lt;/em&gt;
• marine-derived fungus
• DES mutagenesis