PF 1018

A new insecticidal compound PF1018 was isolated from the culture broth of Humicola sp. It exhibited insecticidal activity against a wide range of critical pest species. The structure of PF1018 was determined to be (7aS)-2-((2E)-1-hydroxy-3-((1S,3aR,4R,5R,7aR)-3a,4,5,7 a-tetrahydro-1,3,5,7- tetramethyl-5,1-((3S)-(Z)-2,3-dimethylpropeno)-1H-inden-4-yl )-2- propenylidene)pyrrolizidine-1,3-dione, by NMR spectral analyses coupled with X-ray crystallographic analysis and chemical degradation study.

The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels-Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.

Pericyclic reaction cascades are unparalleled in their ability to quickly generate complex structures with excellent stereocontrol. Herein, the use of a biomimetic Stille/8π electrocyclization/Diels-Alder cascade to successfully assemble the core structure of (-)-PF-1018 is reported.