Synthetic Study of Natural Metabolites Containing a Benzo[ c ]oxepine Skeleton: Heterocornol C and D

• Published in: International journal of molecular sciences Vol. 24; no. 12; p. 10331
• Main Authors: Gettler, Ján, Čarný, Tomáš, Markovič, Martin, Koóš, Peter, Samoľová, Erika, Moncoľ, Ján, Gracza, Tibor
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2023; MDPI
• Subjects: Absolute configuration; Analysis; asymmetric synthesis; benzo[c]oxepin-1-one; Benzoic acid; Chemical properties; Chemical reactions; Configurations; Cross coupling; Enantiomers; heterocornol; Lactones; Metabolites; Metathesis; natural compound; Olefins; Organic acids; Organic compounds; Plant metabolites; polyketide; Polyketides; Potassium; Scientific equipment and supplies industry; Secondary metabolites; Single crystals; Skeleton; Stereoisomerism; Stereoisomers; Synthesis; X ray analysis; United States; Slovakia; asymmetric synthesis; polyketide; benzo[c]oxepin-1-one; heterocornol; natural compound
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241210331

A versatile strategy for the enantioselective synthesis of a benzo[ ]oxepine structural core containing natural secondary metabolites was developed. The key steps of the synthetic approach include ring-closing alkene metathesis for seven-member ring construction, the Suzuki-Miyaura cross-coupling reaction for the installation of the double bond and Katsuki-Sharpless asymmetric epoxidation for the introduction of chiral centers. The first total synthesis and absolute configuration assignment of heterocornol D ( ) were achieved. Four stereoisomers, , - , and - , of this natural polyketide were prepared, starting with 2,6-dihydroxy benzoic acid and divinyl carbinol. The absolute and relative configuration of heterocornol D was assigned via single-crystal X-ray analysis. The extension of the described synthetic approach is further presented with the synthesis of heterocornol C by applying the ether group reduction method to the lactone.