Toward the synthesis of thapsigargin: enantioselective synthesis of 7,11-dihydroxyguaianolides.
[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.
Manzano
Francisco L
FL
Departamento de Química Organica, Facultad de Ciencias, Universidad de Cadiz, Puerto Real, Spain.
Guerra
Francisco M
FM
Moreno-Dorado
F Javier
FJ
Jorge
Zacarías D
ZD
Massanet
Guillermo M
GM
D002384:Catalysis; D015394:Molecular Structure; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D053629:Thapsia / Q000737:chemistry; D019284:Thapsigargin / Q000138:chemical synthesis*
D045789:Sesquiterpenes, Guaiane; D019284:Thapsigargin