Publication
The natural product class of the sorbicillinoids is composed of structurally diverse molecules with many strong, biomedically relevant biological activities. Owing to their complex structures, the synthesis of sorbicillinoids is a challenging task. Here we show the first total synthesis of the fungal sorbicillinoids spirosorbicillinols A-C. The convergent route comprises the chemo-enzymatic transformation of sorbicillin to the highly reactive sorbicillinol and the assembly of scytolide and isomers starting from shikimic and quinic acid analogs. The key step in the total synthesis is the fusion of both building blocks in a Diels-Alder cycloaddition leading to the straightforward formation of the characteristic sorbicillinoid bicyclo[2.2.2]octane backbone. This work provides unifying access to all natural spirosorbicillinols and unnatural diastereomers. Spirosorbicillinols A-C are fungal natural products that display various biological properties, but their total synthesis has yet to be accomplished. Here, the authors report the total synthesis of spirosorbicillinols A-C based on a chemo-enzymatic transformation of sorbicillin into sorbicillinol, which is fused to synthetically prepared scytolide and isomers by a Diels-Alder cycloaddition reaction.