A formal total synthesis of (−)-aspidophytine (2), a key substructure associated with the heterodimeric indole alkaloid haplophytine (1) and itself a natural product, has been established by employing the homochiral and enzymatically derived cis-1,2-dihydrocatechol 8 as a starting material. Specifically, compound 8 has been converted into the pentacyclic product 26, an advanced intermediate associated with a previously reported synthesis of aspidophytine (2). Simple modifications to the reaction sequence have also allowed for the identification of a synthetic pathway leading from dihydrocatechol 8 to (+)-aspidophytine (ent-2).

A chemoenzymatic approach to the title framework is reported. The reaction sequence starts with the whole-cell biotransformation of iodobenzene and the conversion of the resulting homochiral metabolite into a triene that engages in an intramolecular Diels-Alder (IMDA) reaction and so affording an adduct embodying the platencin core. Application of an oxa-di--methane (ODPM) rearrangement to a derivative of this core affords a cyclopropannulated form of the target framework that is then obtained through TMSI-mediated cleavage of the three-membered ring. A strategy for the assembly of the enantiomeric framework is also described.