Synthesis of (Z)-trisubstituted olefins by decarboxylative grob-type fragmentations: epothilone D, discodermolide, and peloruside A.
Methyl-branched (Z)-trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxide- induced Grob-type fragmentation as an easy access to trisubstituted olefins. In our case, beta-mesyloxy delta-lactones with three stereogenic centers were chosen whose fragmentation underlies a high stereoelectronic control. Major challenges in the syntheses were the installation of quaternary stereocenters, achieved by enzymatic desymmetrization of meso-diesters and by aluminium-promoted stereoselective rearrangement of chiral epoxides, respectively. Different aldol strategies were developed for the formation of the fragmentation precursors. Additionally a short survey about nucleophilic additions to aldehydes with quaternary alpha-centers is presented.
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; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000473:Alkanes; D000475:Alkenes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002219:Carbamates; D034261:Epothilones; D007783:Lactones; D011753:Pyrones; C414085:peloruside A; C071229:discodermolide; C114026:desoxyepothilone B