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Concise Total Synthesis of (−)‐Affinisine Oxindole, (+)‐Isoalstonisine, (+)‐Alstofoline, (−)‐Macrogentine, (+)‐ N a ‐Demethylalstonisine, (−)‐Alstonoxine A, and (+)‐Alstonisine
Author(s) -
Stephen Michael Rajesh,
Rahman M. Toufiqur,
Tiruveedhula V. V. N. Phani Babu,
Fonseca German O.,
Deschamps Jeffrey R.,
Cook James M.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703572
Subject(s) - oxindole , pyrrolidine , total synthesis , moiety , stereochemistry , chemistry , stereospecificity , organic chemistry , catalysis
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 7 R or 7 S . 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 (7 R ), as well as (+)‐alstonisine, (+)‐alstofoline, (−)‐alstonoxine A and (+)‐ N a ‐demethylalstonisine from the alstonisine series (7 S ).