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Enantioselective Total Synthesis of (+)‐Ottelione A, (−)‐Ottelione B, (+)‐3‐ epi ‐Ottelione A and Preliminary Evaluation of Their Antitumor Activity
Author(s) -
Araki Hiroshi,
Inoue Munenori,
Suzuki Takeyuki,
Yamori Takao,
Kohno Michiaki,
Watanabe Kazuhiro,
Abe Hideki,
Katoh Tadashi
Publication year - 2007
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.200700789
Subject(s) - enantioselective synthesis , stereochemistry , chemistry , organic chemistry , catalysis
Abstract Enantioselective total synthesis of (+)‐ottelione A ( 1 ) and (−)‐ottelione B ( 2 ), novel and potent antitumor agents from a freshwater plant, and (+)‐3‐ epi ‐ottelione A ( 3 ), the earlier proposed stereostructure of 1 , was efficiently achieved starting from the known tricyclic compound 10 . The synthesis involved the following key steps: i) coupling reactions of aldehydes 8 and 9 with the aromatic portion 7 ( 8 + 7 → 15 and 9 + 7 → 27 ), ii) base‐induced hemiacetal‐opening/epimerization reactions of the cyclic hemiacetals 6 and 27 ( 6 → 17 and 27 a → 26 a ), and iii) Corey–Winter's reductive olefination of the cyclic thiocarbonates 21 and 36 ( 21 → 22 and 36 → 37 ). The present total synthesis fully established the absolute configuration of these natural products. The cell growth inhibition profile, COMPARE analysis, and tubulin inhibitory assay of (+)‐3‐ epi ‐ottelione A ( 3 ) and its O ‐acetyl derivative 24 demonstrated that these unnatural substances could be prominent lead compounds for the development of anticancer agents with a novel mode of action.