Formal Total Syntheses of (+)- and (-)-Aspidophytine from a Common, Homochiral Precursor.

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).

Chemoenzymatic and Enantiomeric Switching Regimes Enabling the Synthesis of Homochiral Cyclohexa-2,5-dienones Incorporating All-Carbon Quaternary Centers.

The enantiomerically pure, bromobenzene-derived metabolite 5 has been transformed into enone 20 using a reaction sequence involving Suzuki-Miyaura cross-coupling and Eschenmoser-Claisen rearrangement processes. Treatment of compound 20 with lithium hydroxide results in an acetonide fragmentation reaction that delivers the 4,4-disubstituted cyclohexa-2,5-dienone 21, reductive de-oxygenation of which leads to congener 22. A closely related sequence of reactions can be used to convert the same homochiral starting material 5 into compound ent-22.

The Application of Dioxygenase-Based Chemoenzymatic Processes to the Total Synthesis of Natural Products.

This Minireview describes the exploitation of certain enzymatically derived, readily accessible, and enantiomerically pure cis-1,2-dihydrocatechols as starting materials in the chemical synthesis of a range of biologically active natural products, most notably sesquiterpenoids and alkaloids.