Ovafolinin A and B, isolated from Lyonia ovalifolia var. elliptica, and Sinocalamus affinis, are lignans which contain a unique tetra- and pentacyclic benzoxepin-bridged aryl tetralin structure. We report the first total synthesis of these natural products, in 14 linear steps, utilising firstly an acyl-Claisen rearrangement (fig. 1) to racemically construct the lignans, allowing conformation of their unique scaffold and determination of relative stereochemistry. The constrained benzoxepin-bridged aryl tetralin was formed in a single step from a linear precursor via a cascade reaction, using a bulky protecting group to place the reactive moieties in the required orientation. Following confirmation of the relative stereochemistry of both ovafolinin A and B, a modified chiral synthesis was used to confirm the absolute stereochemistry. This chiral route utilised an Evan’s chiral oxazolidinone to obtain the same key intermediate, as a single enantiomer (fig. 2), resulting in the first synthesis of enantiopure ovafolinin A and B. Comparison of optical rotation suggests that these compounds are found as scalemic mixtures in nature.

Total synthesis of ovafolinin A and B

256th National Meeting (2018)

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