Total synthesis of (+)-discodermolide: an improved endgame exploiting a Still-Gennari-type olefination with a C1-C8 beta-ketophosphonate fragment.
[structure: see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.
Paterson
Ian
I
University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. ip100@cam.ac.uk
Lyothier
Isabelle
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D000447:Aldehydes / Q000737:chemistry; D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D063065:Organophosphonates / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000473:Alkanes; D000475:Alkenes; D002219:Carbamates; D007659:Ketones; D007783:Lactones; D063065:Organophosphonates; D011753:Pyrones; C071229:discodermolide