fusarisetin-a and equisetin

Total synthesis of cryptocin, a fungus metabolite, was achieved based on the biosynthetic hypothesis. A variety of derivatives of cryptocin, equisetin and fusarisetin A were prepared, wherein the racemization of C-3 and diastereoselectivity of C-5 were investigated. We further examined their inhibitory effects on breast cancer cell survival and metastasis, and summarized the structure-activity relationship.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chemistry Techniques, Synthetic; Heterocyclic Compounds, 4 or More Rings; Humans; Naphthalenes; Oxidation-Reduction; Pyrroles; Pyrrolidinones; Structure-Activity Relationship; Substrate Specificity; Tetrahydronaphthalenes

(+)-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 Mn(III)/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.

Topics: Antineoplastic Agents, Phytogenic; Biomimetics; Cyclization; Cycloaddition Reaction; Heterocyclic Compounds, 4 or More Rings; Oxidation-Reduction; Pyrrolidinones; Stereoisomerism; Tetrahydronaphthalenes