Daldipyrenones A-C: Caged 6,6,6,6,6 Polyketides Derived from an Endolichenic Fungus Daldinia pyrenaica 047188

• Published in: Organic letters 2023-09, Vol.25 (36), p.6725
• Main Authors: Lee, Seungjin, Park, In Guk, Choi, Jin Won, Son, Jin Young, Lee, Jin Woo, Hur, Jae-Seoun, Kim, Youngmee, Nam, Sang-Jip, Kang, Hahk-Soo, Deyrup, Stephen T, Noh, Minsoo, Shim, Sang Hee
• Format: Article
• Language: English
• ISSN: 1523-7052; 1523-7052
• DOI: 10.1021/acs.orglett.3c02583

Daldipyrenones A-C (1-3), three unprecedented caged xanthone [6,6,6,6,6] polyketides featuring a spiro-azaphilone unit, were discovered from an endolichenic fungus, Daldinia pyrenaica 047188. The structures of 1-3 were determined by using spectroscopic analysis and chemical derivatization. Daldipyrenones are likely derived by combining a chromane biosynthesis intermediate, 1-(2,6-dihydroxyphenyl)but-2-en-2-one, and a spiro-azaphilone, pestafolide A, via radical coupling or Michael addition to form a bicyclo[2.2.2]octane ring. Genome sequencing of the strain revealed two separate biosynthetic gene clusters responsible for forming two biosynthetic intermediates, suggesting a proposed biosynthetic pathway. Daldipyrenone A (1) exhibited significant antimelanogenic activity with lower EC50's than positive controls and moderate adiponectin-secretion promoting activity.Daldipyrenones A-C (1-3), three unprecedented caged xanthone [6,6,6,6,6] polyketides featuring a spiro-azaphilone unit, were discovered from an endolichenic fungus, Daldinia pyrenaica 047188. The structures of 1-3 were determined by using spectroscopic analysis and chemical derivatization. Daldipyrenones are likely derived by combining a chromane biosynthesis intermediate, 1-(2,6-dihydroxyphenyl)but-2-en-2-one, and a spiro-azaphilone, pestafolide A, via radical coupling or Michael addition to form a bicyclo[2.2.2]octane ring. Genome sequencing of the strain revealed two separate biosynthetic gene clusters responsible for forming two biosynthetic intermediates, suggesting a proposed biosynthetic pathway. Daldipyrenone A (1) exhibited significant antimelanogenic activity with lower EC50's than positive controls and moderate adiponectin-secretion promoting activity.