Biomimetic Synthesis of Equisetin and (+)-Fusarisetin A

• Published in: Chemistry : a European journal 2013-09, Vol.19 (39), p.13040-13046
• Main Authors: Yin, Jun, Kong, Lili, Wang, Cheng, Shi, Yingbo, Cai, Shujun, Gao, Shuanhu
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antineoplastic Agents, Phytogenic; biomimetic synthesis; Biomimetics; Chemistry; Cyclization; Cycloaddition Reaction; Diels-Alder reactions; equisetin; Esters; Fatty acids; fusarisetin A; Heterocyclic Compounds, 4 or More Rings - chemical synthesis; Heterocyclic Compounds, 4 or More Rings - chemistry; Oxidation; Oxidation-Reduction; Pyrrolidinones - chemical synthesis; Pyrrolidinones - chemistry; radical reactions; Stereoisomerism; Synthesis; Tetrahydronaphthalenes - chemical synthesis; Tetrahydronaphthalenes - chemistry; total synthesis; Unsaturated
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201302163

(+)‐Fusarisetin A belongs to a group of acyl tetramic acid natural products that show potential anticancer activity. Equisetin, a biogenetically related acyl tetramic acid, contains the basic skeleton of (+)‐fusarisetin A. We proposed that equisetin and (+)‐fusarisetin A share a biosynthetic pathway that starts with naturally occurring (S)‐serine and an unsaturated fatty acid. In support of this hypothesis, we have demonstrated that a cyclization sequence involving an intramolecular Diels–Alder reaction followed by a Dieckmann cyclization of polyenoylamino acid yielded equisetin. The aerobic oxidation of equisetin, promoted by either MnIII/O2 or a reactive oxygen species (ROS) produced by visible‐light chemistry, gave peroxyfusarisetin, which could be easily reduced to (+)‐fusarisetin A. We report herein detailed information on the biogenetic synthesis of equisetin and (+)‐fusarisetin A. Make the change to bio! Biomimetic synthesis of equisetin and (+)‐fusarisetin A was achieved based on a biosynthetic hypothesis. An intramolecular Diels–Alder reaction followed by a Dieckmann cyclization of polyenoylamino ester furnished equisetin. The aerobic oxidation of equisetin to give (+)‐fusarisetin A was mediated by a MnIII/O2 system or reactive oxygen species (ROS) (see scheme).