Concise Total Synthesis of (-)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (-)-Macrogentine, (+)-Na -Demethylalstonisine, (-)-Alstonoxine A, and (+)-Alstonisine. Chemistry 2017 Nov 07;23(62):15805-15819
Date
09/07/2017Pubmed ID
28875520Pubmed Central ID
PMC6168078DOI
10.1002/chem.201703572Scopus ID
2-s2.0-85031661673 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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 (+)-Na -demethylalstonisine from the alstonisine series (7S).
Author List
Stephen MR, Rahman MT, Tiruveedhula VVNPB, Fonseca GO, Deschamps JR, Cook JMAuthor
James M. Cook PhD University Distinguished Professor in the Chemistry and Biochemistry department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AlkaloidsCrystallography, X-Ray
Cyclization
Indoles
Molecular Conformation
Spiro Compounds
Stereoisomerism