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

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[pyr...

Full description

Saved in:
Bibliographic Details
Published inChemistry : a European journal Vol. 23; no. 62; pp. 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 Journal Article
LanguageEnglish
Published WEINHEIM Wiley 07.11.2017
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
ASYMMETRIC-SYNTHESIS
SOLVENT-FREE CONDITIONS
alkaloids
STEREOSPECIFIC TOTAL-SYNTHESIS
spirooxindoles
N-FORMYLATION
ENANTIOSPECIFIC TOTAL-SYNTHESIS
ALSTONIA-MACROPHYLLA-WALL
sarpagine
SARPAGINE INDOLE ALKALOIDS
enantiospecific
macroline
total synthesis
ENANTIOSELECTIVE TOTAL-SYNTHESIS
TETHERED VINYL HALIDES
AMINO-ACID ESTERS
Online AccessGet full text

Cover

More Information
Summary: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).
Bibliography:NIH RePORTER
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201703572