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Asymmetric Total Synthesis of (−)‐Stenine and 9a‐ epi ‐Stenine
Author(s) -
Fujioka Hiromichi,
Nakahara Kenji,
Kotoku Naoyuki,
Ohba Yusuke,
Nagatomi Yasushi,
Wang TsungLung,
Sawama Yoshinari,
Murai Kenichi,
Hirano Kie,
Oki Tomohiro,
Wakamatsu Shintaro,
Kita Yasuyuki
Publication year - 2012
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.201200376
Subject(s) - stereocenter , azide , wittig reaction , ring (chemistry) , cyclohexane , staudinger reaction , stereochemistry , chemistry , intramolecular force , total synthesis , stereoselectivity , chiral auxiliary , imine , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis
A route for the asymmetric synthesis of (−)‐stenine, a member of the Stemona alkaloid family used as folk medicine in Asian countries, is described. The key features of the sequence employed include stereoselective transformations on a cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular Mitsunobu reaction to construct the perhydroindole ring system. By using an intermediate in the route to (−)‐stenine, an asymmetric synthesis of 9a‐ epi ‐stenine was also executed. The C(9a) stereocenter in 9a‐ epi ‐stenine was installed by using a Staudinger/aza‐Wittig reaction of a keto–azide precursor followed by reduction of the resulting imine. The results of this effort demonstrate the applicability of the chiral auxiliary based strategy to the preparation of naturally occurring alkaloids that contain highly functionalized cyclohexane cores.