Conocandin

A catalytic diastereoselective sulfonium ylide epoxidation of aldehydes furnished original vinyl epoxides, having an MBH backbone. These highly functionalized building blocks were used for a formal synthesis of the antibiotic conocandin, and opened up a stereodivergent route towards beta-hydroxy-alpha-methylene lactones, core units of naturally occurring compounds. Under acidic conditions, the oxiranes were mainly transformed, with moderate to good yields, into trans beta-hydroxy-alpha-methylene lactones. On the other hand, a user-friendly palladium-catalysed CO2 insertion and cyclisation sequence gave the cis beta-hydroxy-alpha-methylene lactone counterparts along with an interesting cis-trans equilibration of the pi-allyl intermediates.

Herein is a report on the molecular exchange occurring between multilateral symbiosis partners-a tit-for-tat exchange that led to the characterization of two new metabolites, conocandin B (fungal-derived) and dentigerumycin F (bacterial-derived). The structures were determined by NMR, mass spectrometry, genomic analysis, and chemical derivatizations. Conocandin B exhibits antimicrobial activity against both the bacterial symbionts of fungus-growing ant and human pathogenic strains by selectively inhibiting FabH, thus disrupting fatty acid biosynthesis.