Total Synthesis of (-)-Peniphenone A

The Journal of Organic Chemistry
Mathilde PantinDaniel P Furkert

Abstract

The asymmetric total synthesis of the polyketide benzannulated spiroketal natural product, (-)-peniphenone A, is reported. The key reaction in the synthesis involved sp3-sp2 Negishi cross-coupling between a chiral organozinc species and an aryl bromide to construct the challenging α-chiral β-aryl carbonyl motif present in the natural product. Access to the spiroketal possessing the correct stereochemistry was facilitated by an unusual thermodynamic resolution at C10. The synthesis was achieved in 14 steps (longest linear sequence) from commercially available 2,4-dihydroxybenzaldehyde in 6% overall yield. Investigations into a parallel approach required extension of Krische's enantioselective hydrogen-mediated C-C coupling to α-substituted alcohols and oxetane ring-opening with an aryllithium for assembly of the polyketide domain. These studies provide a useful foundation for further work toward the natural product family, members of which demonstrate significant activity against M. tuberculosis and offer continuing inspiration for the development of efficient new chemical methods.

References

Mar 26, 2002·Chemical & Pharmaceutical Bulletin·Haruhiro FujimotoMasami Ishibashi
Nov 22, 2002·Organic Letters·Luiz C DiasJ Zukerman-Schpector
Jul 10, 2003·Angewandte Chemie·Ivan R Corrêa Júnior, Ronaldo A Pilli
Oct 8, 2004·Journal of the American Chemical Society·Jacqueline E Milne, Stephen L Buchwald
Jan 29, 2005·The Journal of Organic Chemistry·William P Gallagher, Robert E Maleczka
Mar 2, 2006·Journal of the American Chemical Society·Peter K ParkJames L Leighton
Apr 3, 2010·European Journal of Medicinal Chemistry·Velimir PopsavinGordana Bogdanović
Jul 22, 2010·Natural Product Reports·Jonathan SperryMargaret A Brimble
Nov 4, 2010·Organic Letters·Ian PatersonS B Jennifer Kan
Oct 6, 2011·Chemistry : a European Journal·Philipp GersbachKarl-Heinz Altmann
Jan 19, 2013·Organic Letters·U Bin KimMargaret A Brimble
Jul 11, 2013·Organic Letters·Justin T J Spence, Jonathan H George
Aug 21, 2013·Organic Letters·Paul A HumeMargaret A Brimble
Nov 29, 2013·Organic Letters·Wei-Zhong LiuRong-Xiu Zhu
May 20, 2016·Scientific Reports·Weiguang SunYonghui Zhang
Aug 10, 2016·The Journal of Organic Chemistry·Rachelle QuachMargaret A Brimble
Aug 23, 2016·Journal of the American Chemical Society·Barry M TrostRainer Kalkofen
Nov 3, 2016·Journal of the American Chemical Society·Inji ShinMichael J Krische

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Citations

Sep 4, 2019·Organic & Biomolecular Chemistry·Rachel M Gillard, Margaret A Brimble
Apr 23, 2020·Frontiers in Pharmacology·Emmanuelle LautiéJean A Boutin
May 30, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Nelson G M GomesPaula B Andrade
Jul 7, 2018·The Journal of Organic Chemistry·Mohammad Movassaghi, Wilfred A van der Donk

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