C-H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity

Angewandte Chemie
Daniel H O' DonovanNuno Maulide

Abstract

We report a novel approach to the classical natural product quinine that is based on two stereoselective key steps, namely a C-H activation and an aldol reaction, to unite the two heterocyclic moieties of the target molecule. This straightforward and flexible strategy enables a concise synthesis of natural (-)-quinine, the first synthesis of unnatural (+)-quinine, and also provides access to unprecedented C3-aryl analogues, which were prepared in only six steps. We additionally demonstrate that these structural analogues exhibit improved antimalarial activity compared with (-)-quinine both in vitro and in mice infected with Plasmodium berghei.

References

Jan 14, 1970·Journal of the American Chemical Society·M UskokovićT Henderson
Jan 14, 1970·Journal of the American Chemical Society·M GatesW L Schreiber
Jul 18, 2001·Journal of the American Chemical Society·G StorkA Fujimoto
Aug 14, 2003·Chemical Reviews·Stefan FranceThomas Lectka
Jan 22, 2004·Journal of the American Chemical Society·Izzat T RaheemEric N Jacobsen
Mar 27, 2004·Chemical Communications : Chem Comm·Jean-Claude BerthetMichel Ephritikhine
Aug 18, 2004·Accounts of Chemical Research·Shi-Kai TianLi Deng
Jan 26, 2005·Angewandte Chemie·Teodoro S Kaufman, Edmundo A Rúveda
Apr 23, 2005·Chemical Communications : Chem Comm·Akira MiyazawaGeorge A Olah
Sep 22, 2005·Journal of the American Chemical Society·Vladimir G ZaitsevOlafs Daugulis
May 26, 2007·Angewandte Chemie·Takashi Ooi, Keiji Maruoka
Dec 13, 2007·Chemical Reviews·Matthew J Gaunt, Carin C C Johansson
Jun 26, 2009·Accounts of Chemical Research·Olafs DaugulisDmitry Shabashov
Sep 30, 2009·Chemical Communications : Chem Comm·Fides BenfattiPier Giorgio Cozzi
Jan 19, 2010·Chemical Reviews·Thomas W Lyons, Melanie S Sanford
May 26, 2011·Malaria Journal·Jane AchanUmberto D'Alessandro
Apr 20, 2012·Bioorganic & Medicinal Chemistry·Theresa DinioJeremy B Morgan
Aug 15, 2013·Organic Letters·Daniela Sustac Roman, André B Charette
Oct 5, 2013·The Journal of Organic Chemistry·Enrico T NadresOlafs Daugulis
Aug 5, 2014·Organic Letters·Wei CuiHonggen Wang
Jul 13, 2017·Chemical Reviews·Jian HeJin-Quan Yu

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Citations

Nov 6, 2018·Angewandte Chemie·Jaehoo Lee, David Y-K Chen
Feb 29, 2020·Chemical Science·Shinya ShiomiHayato Ishikawa
Feb 25, 2021·Organic Letters·Francesco TrentiSarah E O'Connor
Dec 5, 2020·ACS Central Science·Iakovos SaridakisNuno Maulide
Jul 3, 2019·Accounts of Chemical Research·Xiao-Yu Liu, Yong Qin
Aug 7, 2019·The Journal of Organic Chemistry·Diego Alemán-Ponce de LeónLuis A Polindara-García
May 16, 2019·Journal of the American Chemical Society·Benedikt S Schreib, Erick M Carreira
Oct 2, 2021·Chemical Communications : Chem Comm·Ranjan JanaEnakshi Dinda

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