Total synthesis of gambierol: subunit coupling and completion.
The preceding manuscript detailed our synthesis of the gambierol A-C and F-H ring precursors. Reported herein is a description of the coupling of the two precursors and the conversion of the coupled material into gambierol. Coupling of the subunits involved ester formation, enol ether RCM, and mixed thioketal formation and reduction. By employing this strategy we were able to bring highly advanced subunits into the coupling and, as a result, we were able to minimize the number of post-coupling transformations required to complete gambierol. At the completion of the synthesis, we generated 7.5 mg (1.5 % overall yield) of (-)-gambierol in 44 steps (longest linear sequence).
Johnson
Henry W B
HW
University of Utah, Department of Chemistry, 315 South 1400 East, Salt Lake City, Utah 84112, USA.
Majumder
Utpal
U
Rainier
Jon D
JD
D002384:Catalysis; D002922:Ciguatoxins / Q000138:chemical synthesis*; D003500:Cyclization; D004952:Esters / Q000138:chemical synthesis; D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D035964:Oxocins
D002922:Ciguatoxins; D004952:Esters; D004988:Ethers, Cyclic; D007202:Indicators and Reagents; D011083:Polycyclic Compounds; C435770:gambierol; D035964:Oxocins