Catalytic asymmetric total syntheses of quinine and quinidine.

The catalytic, asymmetric syntheses of quinine and quinidine were achieved in 16 steps. The recently developed salen(Al)-catalyzed enantioselective Michael addition of methyl cyanoacetate served to set the crucial C4 stereocenter in 92% ee, and a late-stage asymmetric dihydroxylation was used to differentiate the common intermediate and access the two desired diastereomeric products with high selectivity.

• Publication year

  2004

• Venue

  Journal of the American Chemical Society

• Publication date

  2004-01-28

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/JA039550YPMID 14733531
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Enantioselective Michael additions to alpha,beta-unsaturated imides catalyzed by a Salen-Al complex.

  2003cited by this paper
• Privileged Chiral Catalysts

  2003cited by this paper
• The first stereoselective total synthesis of quinine.

  2001cited by this paper
• Catalytic Asymmetric Synthesis of Epoxides from Aldehydes Using Sulfur Ylides with In Situ Generation of Diazocompounds.

  2001cited by this paper
• To the Best of Our Knowledge

  1979cited by this paper
• Chapter 16 The Chemistry of the Cinchona Alkaloids

  1953cited by this paper

• Catalytic Enantioselective Diboration of 1,2-Dihydropyridines.

  2025cites this paper
• C‐2′ Substituted Cinchona Alkaloid Polymeric Catalyst in Malononitrile to Chalcone Reactions

  2025cites this paper
• The Quinine Odyssey: A Barometer of the State of Organic Synthesis Over Centuries.

  2024cites this paper
• Enantioselective total syntheses of (−)-mitragynine, (−)-quinine and (+)-quinidine enabled by Ir-catalysed asymmetric hydrogenation of all-carbon tetrasubstituted cycloalkenes

  2024cites this paper
• Recent advances in the total synthesis of alkaloids using chiral secondary amine organocatalysts.

  2024cites this paper
• Crecimiento vegetativo de Cinchona officinalis l. inoculado con hongos micorrízicos arbusculares nativos y abonado orgánico

  2024cites this paper
• Enantioselective Nitrene Transfer to Hydrocinnamyl Alcohols and Allylic Alcohols Enabled by Systematic Exploration of the Structure of Ion-Paired Rhodium Catalysts

  2024cites this paper
• Growing Utilization of Radical Chemistry in the Synthesis of Pharmaceuticals

  2023cites this paper
• Synthesis of cinchona urea polymers using Yamamoto coupling and their application to asymmetric reaction.

  2023cites this paper
• NHPI-Mediated Electrochemical α-Oxygenation of Amides to Benzimides.

  2023cites this paper
• Cinchona alkaloids – acid, anion-driven fluorescent INHIBIT logic gates with a receptor1–fluorophore–spacer–receptor2 format and PET and ICT mechanisms

  2023cites this paper
• A New Continuous Flow Microwave Radiation Process Design for Non-Isocyanate Polyurethane (NIPU)

  2023cites this paper
• Ni-Catalyzed 1,2-Alkyl Borylation and Silylation of Allenes En Route to [1,3]-Bis-Organometallic Reagents.

  2023cites this paper
• Total Syntheses of Cinchona Alkaloids via Photoredox-Catalyzed Deoxygenative Arylation.

  2023cites this paper
• Organocatalyst-mediated five-pot synthesis of (–)-quinine

  2022cites this paper
• Electrochemically driven stereoselective approach to syn-1,2-diol derivatives from vinylarenes and DMF†

  2021cites this paper
• Transition metal-catalysed reactions: Diastereoselectivity and asymmetric synthesis

  2021cites this paper
• Multiplicación clonal del árbol de la quina (Cinchona officinalis): una alternativa para conservar el árbol nacional de Perú

  2021cites this paper
• A Review on Synthesis of Quinoline Analogs as Antimalarial, Antibacterial and Anticancer agents

  2021cites this paper
• Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A4 Mimetics (QNX-sLXms)

  2021cites this paper
• Diastereoselective Copper-Mediated Conjugate Addition of Functionalized Magnesiates for the Preparation of Bisaryl Nrf2 Activators.

  2021cites this paper
• Influences of controlled microwave field radiation on pore structure, surface chemistry and adsorption capability of gas-bearing shales

  2021cites this paper
• Oxidations and Reductions

  2020cites this paper
• Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.

  2020cites this paper
• Steps Toward the Synthesis of 1,1'-Dideaza-Quinine: A Proof of Concept

  2020cites this paper
• Catalyst Free Hydroxyl Protection of Quinine via Esterification

  2019cites this paper
• Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction

  2019cites this paper
• Cinchona Alkaloids-Derivatives and Applications.

  2019cites this paper
• Enantioselective total synthesis of the unnatural enantiomer of quinine

  2019cites this paper
• Total Asymmetric Synthesis of Quinine, Quinidine, and Analogues via Catalytic Enantioselective Cascade Transformations

  2019cites this paper
• Bioinspired Synthesis of (+)-Cinchonidine Using Cascade Reactions.

  2018cites this paper
• Substrate Directed Asymmetric Reactions.

  2018cites this paper
• C−H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity

  2018cites this paper
• Time-Dependent Formulation of Resonance Raman Optical Activity Spectroscopy.

  2018cites this paper
• A cascade synthesis of S-allyl benzoylcarbamothioates via Mumm-type rearrangement.

  2018cites this paper
• Chinin, ein legendäres Alkaloid

  2018cites this paper
• Investigating the local structure of B-site cations in (1-x)BaTiO3–xBiScO3 and (1-x)PbTiO3–xBiScO3 using X-ray absorption spectroscopy

  2018cites this paper
• Respuesta de la Cinchona officinalis L. al método de propagación asexual mediante estacas y esquejes

  2018cites this paper
• DBU‐Mediated Intermolecular 5‐exo‐dig Cyclization of PropargylAlcohols and Carbon Disulfide to [1,3]‐Oxathiole‐2‐thiones

  2018cites this paper
• A Local-Desymmetrization-Based Divergent Synthesis of Quinine and Quinidine.

  2018cites this paper
• Direct Access of the Chiral Quinolinyl Core of Cinchona Alkaloids via a Brønsted Acid and Chiral Amine Co-catalyzed Chemo- and Enantioselective α-Alkylation of Quinolinylmethanols with Enals.

  2018cites this paper
• C‐H‐Aktivierung ermöglicht eine kurze Totalsynthese von Chinin und Analoga mit erhöhter Anti‐Malaria‐Aktivität

  2018cites this paper
• Transition-metal-free insertion reactions of alkynes into the C-N σ-bonds of imides: synthesis of substituted enamides or chromones.

  2018cites this paper
• Origin of and a Solution for Uneven Efficiency by Cinchona Alkaloid-Derived, Pseudoenantiomeric Catalysts for Asymmetric Reactions.

  2018cites this paper
• A minireview of effects of maternal diet during pregnancy on postnatal vegetable consumption: Implications for future research (a new hypothesis) and recommendations

  2018cites this paper
• Vanadium-Catalyzed Oxidative C(CO)-C(CO) Bond Cleavage for C-N Bond Formation: One-Pot Domino Transformation of 1,2-Diketones and Amidines into Imides and Amides.

  2017cites this paper
• Synthesis, Structural Characterization and Antinociceptive Activities of New Arylated Quinolines via Suzuki-Miyaura Cross Coupling Reaction.

  2017cites this paper
• Recent Advances in Boron-Substituted 1,3-Dienes Chemistry: Synthesis and Application.

  2017cites this paper
• Diastereoselective Borocyclopropanation of Allylic Ethers Using a Boromethylzinc Carbenoid.

  2017cites this paper
• Directing Stem Cell Fate: The Synthetic Natural Product Connection.

  2017cites this paper
• Metal-Catalyzed Asymmetric Michael Addition in Natural Product Synthesis.

  2017cites this paper
• Unusual oxidative Smiles reaction of quinine 1,10-phenanthro-2-yl-thioether with SO2 extrusion

  2017cites this paper
• Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C-N Bonds in Total Synthesis.

  2016cites this paper
• The Catalytic, Enantioselective Michael Reaction

  2016cites this paper
• Analytics of Quinine and its Derivatives

  2016cites this paper
• Urea-Functionalized Self-Assembled Molecular Prism for Heterogeneous Catalysis in Water.

  2016cites this paper
• Synthetic and Organocatalytic Studies of Quinidine Analogues with Ring-Size Modifications in the Quinuclidine Moiety.

  2016cites this paper
• One‐Pot Assembly of Fused Heterocycles via Oxidative Palladium‐Catalyzed Cyclization of Arylols and Iodoarenes

  2016cites this paper
• Synthesis and initial evaluation of quinoline-based inhibitors of the SH2-containing inositol 5'-phosphatase (SHIP).

  2015cites this paper
• Quinine. Cinchona Alkaloids (Tryptophan Derived Quinoline Alkaloids)

  2015cites this paper
• Lewis Acid–Brønsted Base Catalysis

  2015cites this paper
• Synthesis of 4-amino-2-trifluormethyl quinoline derivatives via palladium-catalyzed cascade reactions of isocyanides with N-(ortho-iodo)aryl enamines

  2015cites this paper
• Alkaloids. General Introduction

  2015cites this paper
• A combined experimental and theoretical studies on FT-IR, FT-Raman and UV-vis spectra of 2-chloro-3-quinolinecarboxaldehyde.

  2015cites this paper
• Design, synthesis, and biological evaluation of air-stable nafuredin-γ analogs as complex I inhibitors.

  2015cites this paper
• An Enantioselective Synthesis of Substituted Cyclohexanone Derivatives with an All‐Carbon Quaternary Stereocenter by Using an Organocatalytic Asymmetric Domino Double Michael Addition

  2015cites this paper
• Cinchona Alkaloids from Cinchona succirubra and Cinchona ledgeriana

  2014cites this paper
• Mechanistic investigation of the reaction of epoxides with heterocumulenes catalysed by a bimetallic aluminium salen complex.

  2014cites this paper
• Total synthesis of biologically active natural products based on highly selective synthetic methodologies.

  2014cites this paper
• VanadiumV(salen) catalysed synthesis of oxazolidinones from epoxides and isocyanates

  2014cites this paper
• Synthesis of Quinuclidines by Intramolecular Silver-Catalysed Amine Additions to Alkynes

  2014cites this paper
• Organocatalysis in Enantioselective α-Functionalization of 2-Cyanoacetates

  2014cites this paper
• Synthesis of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(arylamino)prop-2-en-1-one: advances in the mechanism of Combes 2-trifluoromethyl and 2-perfluoroalkyl quinolines synthesis

  2014cites this paper
• Development of HB Donor Catalysts

  2013cites this paper
• Approach Toward the Total Synthesis of Lundurines

  2013cites this paper
• Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

  2013cites this paper
• Cincholenines A and B, two unprecedented quinoline alkaloids from Cinchona ledgeriana

  2013cites this paper
• α-Isocupreine, an enantiocomplementary catalyst of β-isocupreidine.

  2013cites this paper
• Synthesis and Antimicrobial Activity of 3-Cyano-4-imino-9-methoxy-4H-pyrimido [2, 1-b] pyrimido [4, 5-b] quinoline and 2-Substituted Derivatives

  2013cites this paper
• Bimetallic Aluminum(salen) Catalyzed Synthesis of Oxazolidinones from Epoxides and Isocyanates

  2013cites this paper
• Natural Product Synthesis

  2013cites this paper
• Synthesis and Single Crystal X-ray Studies of 3-(3,5-Bis(trifluoromethyl)phenyl) Quinoline and 3-(4-Fluoro-3-methylphenyl) Quinoline

  2013cites this paper
• Cuantificación de quinina en extractos de Cinchona pubescens y evaluación de la actividad antiplasmodial y citotóxica

  2013cites this paper
• Asymmetric Epoxidation of Chromenes Using Manganese(III) Complexes with Novel Chiral Salen-like Schiff Base Ligands

  2012cites this paper
• Simple chiral sulfonamide primary amine catalysed highly enantioselective Michael addition of malonates to enones.

  2012cites this paper
• Scope of stereoselective Mn-mediated radical addition to chiral hydrazones and application in a formal synthesis of quinine.

  2012cites this paper
• n-Butylammonium carboxylates/Tf2O: ionic liquid based systems for the synthesis of unsymmetrical imides via a Ritter-type reaction

  2012cites this paper
• Nature’s Chiral Catalyst and Anti-Malarial Agent: Isolation and Structure Elucidation of Cinchonine and Quinine from Cinchona calisaya

  2012cites this paper
• Highly enantioselective conjugate addition of malononitrile to 2-enoylpyridines with bifunctional organocatalyst.

  2012cites this paper
• Literature Survey Part B: Miscellaneous Organic Transformations

  2012cites this paper
• The Woodward Research Institute, Robert Burns Woodward (1917–1979) and Chemistry behind the Glass Door

  2011cites this paper
• Bimetallic aluminium(acen) complexes as catalysts for the synthesis of cyclic carbonates from carbon dioxide and epoxides

  2011cites this paper
• Asymmetric organocatalytic reactions by bifunctional amine-thioureas

  2011cites this paper
• Organocatalytic asymmetric synthesis of quinine and quinidine

  2011cites this paper
• Enantioselective Organocatalytic Synthesis of Medicinally Privileged 2-Amino-4H-chromene-3-carbonitriles via a Cascade Process.

  2011cites this paper
• Influence of flue gas on the catalytic activity of an immobilized aluminium(salen) complex for cyclic carbonate synthesis

  2011cites this paper
• Aqueous ethanol: a suitable medium for the diastereoselective Diels–Alder reaction mediated by chiral bases

  2011cites this paper
• SYNTHESIS OF NOVEL QUININE DERIVATIVES VIA THE HECK REACTION

  2011cites this paper
• Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: formal synthesis of quinine.

  2011cites this paper
• Structure, Properties, and Preparation of Boronic Acid Derivatives

  2011cites this paper