Total Synthesis of Isomalabaricane Triterpenoids
datasetposted on 27.08.2019, 21:13 by Yaroslav D. Boyko, Christopher J. Huck, David Sarlah
The first total syntheses of (±)-rhabdastrellic acid A and (±)-stelletin E, highly cytotoxic isomalabaricane triterpenoids, have been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The exceptionally strained trans-syn-trans-perhydrobenz[e]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner through a rapid, complexity-generating sequence. This process features a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung α-substitution of a p‑toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.
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geranylacetoneconcertrhabdastrellictoluenesulfonylhydrazonemannerprocess featuresacidtrans-syn-translate-stage cross-couplingfamily memberssyntheticallystelletinstrategyapproachIsomalabaricane Triterpenoidsside chainspolyene cyclizationumpolung α- substitutioncorecomplexity-generating sequencemarine triterpenoidssynthese14 stepsreductive transpositionperhydrobenzoxidative Rautenstrauch cycloisomerizationcytotoxic isomalabaricane triterpenoidsTotal Synthesistrans-syn-tranindenesynthesis