Open AccessEnantioselective Total Synthesis of (+)-EBC-23, a Potent Anticancer Agent from the Australian Rainforest
Author(s) -
Arun K. Ghosh,
CheSheng Hsu
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c00172
Subject(s) - enantioselective synthesis , sharpless asymmetric dihydroxylation , total synthesis , chemistry , hydrogenolysis , noyori asymmetric hydrogenation , stereochemistry , ketone , cycloaddition , dihydroxylation , epimer , organic chemistry , catalysis
We describe here an enantioselective synthesis of (+)-EBC-23, a potent anticancer agent from the Australian rainforest. Our convergent synthesis features a [3+2] dipolar cycloaddition of an olefin-bearing 1,3- syn diol unit and an oxime segment containing 1,2- syn diol functionality as the key step. The segments were synthesized in a highly enantioselective manner using Noyori asymmetric hydrogenation of a β-keto ester and Sharpless asymmetric dihydroxylation of an α,β-unsaturated ester. Cycloaddition provided isoxazoline derivative which upon hydrogenolysis furnished the β-hydroxy ketone expediently. A one-pot, acid-catalyzed reaction removed the isopropylidene group, promoted spirocyclization, constructed the complex spiroketal lactone core, and furnished EBC-23 and its C11 epimer. The C11 epimer was also converted to EBC-23 by chemoselective oxidation and reduction sequence. The present synthesis provides convenient access to this family of natural products in an efficient manner.