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Concise total synthesis of (-)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (-)-Macrogentine, (+)-N-a-Demethylalstonisine, (-)-AlstonoxineA, and (+)-Alstonisine
Stephen, M. R., Rahman, M. T., Tiruveedhula, V. V. N. P. B., Fonseca, G. O., Deschamps, J. R., & Cook, J. M. (2017). Concise total synthesis of (-)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (-)-Macrogentine, (+)-N-a-Demethylalstonisine, (-)-AlstonoxineA, and (+)-Alstonisine. Chemistry-A European Journal, 23(62), 15805-15819. https://doi.org/10.1002/chem.201703572
A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available d-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro--carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet-Spengler reaction and Dieckmann cyclization, which were scalable to the 600 and 150gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (-)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (-)-alstonoxineA and (+)-N-a-demethylalstonisine from the alstonisine series (7S).