Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D.
Discriminating elimination: A new method for the synthesis of methyl-branched trisubstituted Z olefins, a structural motif in many polyketides with anticancer activity, relies on an (-)OH-induced decarboxylative Grob-type fragmentation (see scheme; Ms = mesyl). The starting materials are beta-mesyloxy lactones with a quaternary alpha center, which are prepared by aldol reactions in a diastereo- and enantioselective manner.
Prantz
Kathrin
K
Institute of Organic Chemistry, University of Vienna, Währingerstrasse 38, 1090 Vienna, Austria.
Mulzer
Johann
J
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000473:Alkanes; D000475:Alkenes; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002219:Carbamates; D034261:Epothilones; D007783:Lactones; D011753:Pyrones; C414085:peloruside A; D017665:Hydroxyl Radical; C071229:discodermolide; C114026:desoxyepothilone B