Progress towards the total synthesis of the welwitindolinone alkaloids and the discovery of a novel tandem O-H insertion conia-ene cyclization

The broth of blue-green algae Hapalosiphon wewitschii and Westiella intricate was shown to possess interesting biological activity, including insecticidal and Pglycoprotein inhibiting capabilities. Upon further investigation, the welwitindolinone alkaloids were isolated from the lipophilic extracts and shown to be responsible for the observed biological activity. Herein are described efforts towards the total synthesis of the welwitindolinone alkaloids and novel chemistry developed in the process.;In efforts towards N-methylwelwitindolinone C isothiocyanate, we employed a sequential O--H insertion Claisen rearrangement to provide compounds capable of undergoing a [3+2] dipolar cycloaddition to access the bicyclo[4.3.1] core. Attempts to install the requisite quaternary center of N-methylwelwitindolinone C isothiocyanate during the [3+2] dipolar cycloaddition event were unsuccessful. Ultimately, a chloronium-ion semi-Pinacol rearrangement was utilized to install the key quaternary center.;Due to complications encountered during the synthesis of N-methylwelwitindolinone C isothiocyanate we shifted our focus to N-methylwelwitindolinone D isonitrile. Investigation into the construction of the bridged ether embedded within N-methylwelwitindolinone D isonitrile led to the discovery of a novel tandem O--H insertion Conia-ene cyclization.