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Potent and Readily Accessible Bistramide A Analogues through Diverted Total Synthesis
Author(s) -
Hanna Ramsey D.,
Naro Yuta,
Deiters Alexander,
Floreancig Paul E.
Publication year - 2018
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.201804417
Subject(s) - natural product , chemistry , total synthesis , ketone , alcohol , sequence (biology) , potency , stereochemistry , combinatorial chemistry , oxygenation , convergent synthesis , biochemistry , organic chemistry , in vitro , biology , ecology
A diverted total synthesis effort is described that is designed to prepare potent cytotoxins based on the actin‐binding natural product bistramide A. The major focus of this study is the preparation of analogues that contain oxygenation at the C29 position, which is necessary for a key reaction in the sequence but is not present in the natural product. This process showed that C29 ketone analogues are accessed more readily and show similar potency compared to the natural product. The ability to incorporate C29 oxygenation and to replace a secondary alcohol by a primary alcohol allowed for the development of a more convergent approach that provides a potent analogue in just eight steps in its longest linear sequence.