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Total Synthesis of Apoptolidin: Part 2. Coupling of Key Building Blocks and Completion of the Synthesis
Author(s) -
Nicolaou K. C.,
Li Yiwei,
Fylaktakidou Konstantina C.,
Mitchell Helen J.,
Sugita Kazuyuki
Publication year - 2001
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/1521-3773(20011015)40:20<3854::aid-anie3854>3.0.co;2-d
Subject(s) - stereocenter , key (lock) , ring (chemistry) , retrosynthetic analysis , combinatorial chemistry , total synthesis , stereochemistry , chemistry , computer science , organic chemistry , enantioselective synthesis , computer security , catalysis
No less than 30 stereogenic elements , a highly unsaturated 20‐membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin ( 1 ) a challenging synthetic target. The retrosynthetic analysis revealed five key building blocks—three for the construction of the macrolide ring B and two prospective pendant saccharide units—which were synthesized in a highly convergent manner and then connected. Apoptolidin's rather labile nature proved particularly challenging in the final deprotection, purification, and characterization procedures.