Concise Total Synthesis of (-)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (-)-Macrogentine, (+)-N a -Demethylalstonisine, (-)-Alstonoxine A, and (+)-Alstonisine

• Published in: Chemistry : a European journal 2017-11, Vol.23 (62), p.15805-15819
• Main Authors: Stephen, Michael Rajesh, Rahman, M Toufiqur, Tiruveedhula, V V N Phani Babu, Fonseca, German O, Deschamps, Jeffrey R, Cook, James M
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Crystallography, X-Ray; Cyclization; Indoles - chemical synthesis; Indoles - chemistry; Molecular Conformation; Oxindoles; Spiro Compounds; Stereoisomerism
• ISSN: 0947-6539; 1521-3765
• DOI: 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-β-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 150 gram 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, (-)-alstonoxine A and (+)-N -demethylalstonisine from the alstonisine series (7S).