Abstract
Herein, we detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints. Efforts toward accessing the common intermediate through a convergent and modular approach resulted in the discovery of a sterically encumbered photoredox catalyst that can selectively generate carbonyl ylides from electron-rich epoxides. These can undergo concerted [3 + 2] dipolar cycloadditions to afford tetrahydrofurans, which were advanced (2-4 steps) to at least one representative natural product or natural product scaffold within all six subtypes in classical lignans. The application of those synthetic blueprints to the synthesis of heterolignans bearing unnatural functionality was demonstrated, which establishes the potential of this strategy to accelerate structure-activity-relationship studies of these natural product frameworks and their rich biological activity.
Highlights
Classical lignans (CLs) represent one of the oldest known and most sought a er families of secondary metabolites found in planta.1 The interest in these molecules is well merited, as they possess a broad spectrum of promising biological actions, some of which have already signi cantly impacted society.2 their carbon frameworks are only composed of two phenylpropane units like 1 (Scheme 1), CLs exhibit wide structural diversity and oxidation patterns that extend to six different subtypes, namely, dibenzylbutane (CL1), dibenzylbutyrolactone (CL2), arylnaphthalene and its derivatives (CL3), dibenzocyclooctadiene (CL4), furan (CL5a–c), and furofuran (CL6)
We detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints
We report a uni ed synthetic approach to CLs and demonstrate how the outlined synthetic blueprints are amenable to the synthesis of heterolignans, which can accelerate the investigation of promising biological functions that each subtype displays outside its natural framework
Summary
Classical lignans (CLs) represent one of the oldest known and most sought a er families of secondary metabolites found in planta.1 The interest in these molecules is well merited, as they possess a broad spectrum of promising biological actions, some of which have already signi cantly impacted society.2 their carbon frameworks are only composed of two phenylpropane units like 1 (Scheme 1), CLs exhibit wide structural diversity and oxidation patterns that extend to six different subtypes, namely, dibenzylbutane (CL1), dibenzylbutyrolactone (CL2), arylnaphthalene and its derivatives (CL3), dibenzocyclooctadiene (CL4), furan (CL5a–c), and furofuran (CL6). In 2017, we reported our efforts on exploring the scope of carbonyl ylide formation and its [3 + 2] dipolar cycloaddition.10 We found some success using DCA, but when expanding the scope to more electron-rich epoxides bearing multiple aryl methoxy groups, characteristic of CL natural products, the reaction failed.11 For example, whereas the carbonyl ylide from epoxide 6 (Scheme 2a) could be trapped with modest efficiency with dimethyl fumarate [8], epoxide 7 would remain unreacted, only providing trace amounts of the desired product 10.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
