Magnesiate Addition/Ring-Expansion Strategy To Access the 6–7–6 Tricyclic Core of Hetisine-Type C20-Diterpenoid Alkaloids

• DOI: 10.1021/acs.orglett.7b02260
• Publication Date: 2017-08-18T19:37:33Z
• Authors: Jason J. Pflueger; Louis C. Morrill; Justine N. deGruyter; Melecio A. Perea; Richmond Sarpong
• Keywords: Molecular Structure; Organic Chemistry; Stereoisomerism; 540; 01 natural sciences; 0104 chemical sciences; Alkaloids; Chemical sciences; Cyclization; Chemical Sciences; Diterpenes; Oxidation-Reduction

A synthetic strategy to access the fused 6-7-6 tricyclic core of hetisine-type C20-diterpenoid alkaloids is reported. This strategy employs a Diels-Alder cycloaddition to assemble a fused bicyclic anhydride intermediate, which is elaborated to a vinyl lactone-acetal bearing an aromatic ring in five steps. Aromatic iodination is followed by magnesium-halogen exchange with a trialkyl magnesiate species, which undergoes intramolecular cyclization. Subsequent oxidation provides the desired 6-7-6 tricyclic diketoaldehyde, with carbonyl groups at all three positions for eventual C-N bond formation and subsequent elaboration.