Vallesamidine and schizozygane alkaloids: rearranged monoterpene indole alkaloids and synthetic endeavours

Covering 1963 to 2023Monoterpene indole alkaloids are the main sub-family of indole alkaloids with fascinating structures, stereochemistry, and diverse bioactivities (e.g., anticancer, anti-malarial and anti-arrhythmic etc.). Vallesamidine alkaloids and structurally more complex schizozygane alkaloids are small groups of rearranged monoterpene indole alkaloids with a unique 2,2,3-trialkylated indoline scaffold, while schizozygane alkaloids can generate a further rearranged skeleton, isoschizozygane, possessing a tetra-substituted, bridged tetrahydroquinoline core. In this review, the origin and structural features of vallesamidine and schizozygane alkaloids are introduced, and a discussion on the relationship of these alkaloids with aspidosperma alkaloids and a structural rearrangement hypothesis based on published studies is followed. Moreover, uncommon skeletons and potential bioactivities, such as anti-malarial and anti-tumour activities, make such alkaloids important synthetic targets, attracting research groups globally to accomplish total synthesis, resulting in impressive works on novel total synthesis, formal synthesis, and construction of key intermediates. These synthetic endeavours are systematically reviewed and highlighted with key strategies and efficiencies, providing different viewpoints on molecular structures and promoting the extension of chemical space and mining of new active scaffolds.