A Two-Step Process for the Synthesis of Hydroxytyrosol.

A new process for the synthesis of hydroxytyrosol (3,4-dihydroxyphenylethanol), the most powerful natural antioxidant currently known, by means of a two-step approach is reported. Catechol is first reacted with 2,2-dimethoxyacetaldehyde in basic aqueous medium to produce the corresponding mandelic derivative with >90 % conversion of the limiting reactant and about 70 % selectivity to the desired para-hydroxyalkylated compound. Thereafter, the intermediate is hydrogenated to hydroxytyrosol by using a Pd/C catalyst, with total conversion of the mandelic derivative and 68 % selectivity. This two-step process is the first example of a synthetic pathway for hydroxytyrosol that does not involve the use of halogenated components or reduction methodologies that produce stoichiometric waste. It also avoids the complex procedure currently used for hydroxytyrosol purification when it is extracted from wastewater of olive oil production.

• Publication year

  2018

• Venue

  ChemSusChem

• Publication date

  2018-06-11

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/cssc.201800684PMID 29761656
• 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.

• High quality, good health: The case for olive oil

  2017cited by this paper
• Emerging Technologies for Recovery of Value-Added Components from Olive Leaves and Their Applications in Food/Feed Industries

  2017cited by this paper
• Current status and future challenges of table olive processing wastewater valorization

  2016cited by this paper
• Life Cycle Assessment of Catechols from Lignin Depolymerization

  2016cited by this paper
• Membrane-Filtered Olive Mill Wastewater: Quality Assessment of the Dried Phenolic-Rich Fraction.

  2016cited by this paper
• Selective isolation of valuable biophenols from olive mill wastewater

  2016cited by this paper
• Catechol production from lignin by Al-doped mesoporous silica catalytic cracking

  2016cited by this paper
• Extraction, benefits and valorization of olive polyphenols

  2016cited by this paper
• Valorisation of food residues: waste to wealth using green chemical technologies

  2013cited by this paper
• Influence of Hydrogen in Catalytic Deoxygenation of Fatty Acids and Their Derivatives over Pd/C

  2012cited by this paper
• Conversion of lignin to aromatic-based chemicals (L-chems) and biofuels (L-fuels).

  2012cited by this paper
• Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review

  2012cited by this paper
• Depolymerization of steam-treated lignin for the production of green chemicals.

  2011cited by this paper
• The molecular basis of working mechanism of natural polyphenolic antioxidants

  2011cited by this paper
• The neuroprotective effect of olive leaf extract is related to improved blood-brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia.

  2011cited by this paper
• Recent patents in olive oil industry: New technologies for the recovery of phenols compounds from olive oil, olive oil industrial by-products and waste waters.

  2010cited by this paper
• E factors, green chemistry and catalysis: an odyssey.

  2008cited by this paper
• Antioxidants

  2008cited by this paper
• Convenient synthesis of hydroxytyrosol and its lipophilic derivatives from tyrosol or homovanillyl alcohol.

  2008cited by this paper
• Hydroxytyrosol and Derivatives: Isolation, Synthesis, and Biological Properties

  2008cited by this paper
• Phenolic molecules in virgin olive oils: a survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade.

  2007cited by this paper
• The E Factor: fifteen years on

  2007cited by this paper
• Mild photochemical synthesis of the antioxidant hydroxytyrosol via conversion of tyrosol.

  2007cited by this paper
• High-yielding preparation of a stable precursor of hydroxytyrosol by total synthesis and from the natural glycoside oleuropein.

  2007cited by this paper
• An overview on olive mill wastes and their valorisation methods.

  2006cited by this paper
• Influence of Alkali Metal Cations upon the Kolbe-Schmitt Reaction Mechanism

  2006cited by this paper
• Tyrosol to hydroxytyrosol biotransformation by immobilised cell extracts of Pseudomonas putida F6

  2006cited by this paper
• Bioavailability and antioxidant effects of olive oil phenols in humans: a review

  2004cited by this paper
• Antioxidant and other biological activities of phenols from olives and olive oil

  2002cited by this paper
• Major phenolic compounds in olive oil: metabolism and health effects.

  2002cited by this paper
• Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil.

  2001cited by this paper
• The antioxidant/anticancer potential of phenolic compounds isolated from olive oil.

  2000cited by this paper
• High Selectivity in the Oxidation of Mandelic Acid Derivatives and in O-Methylation of Protocatechualdehyde: New Processes for Synthesis of Vanillin, iso-Vanillin, and Heliotropin

  2000cited by this paper
• Phenolic compounds and squalene in olive oils: the concentration and antioxidant potential of total phenols, simple phenols, secoiridoids, lignansand squalene.

  2000cited by this paper
• Olive-oil consumption and health: the possible role of antioxidants.

  2000cited by this paper
• Atom efficiency and catalysis in organic synthesis

  2000cited by this paper
• Phenolic Compounds in Different Olive Varieties.

  1998cited by this paper
• Oxidation reactions with in situ generated oxidants

  1998cited by this paper
• Free radical-scavenging properties of olive oil polyphenols.

  1998cited by this paper
• Hydroquinone and Pyrocatechol Production by Direct Oxidation of Phenol

  1976cited by this paper
• The Kolbe-Schmitt Reaction

  1957cited by this paper

• Synthesis, structure, and properties of ultra-high-temperature-resistant biomass-based epoxy resin insulation materials

  2026cites this paper
• Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli

  2025cites this paper
• NaBr-Mediated Electrochemical Hydration of Alkenes: A Minimalist Synthesis of Anti-Markovnikov Alcohol.

  2025cites this paper
• Recent Advances in the Biological Synthesis of l-Tyrosine Derivatives by Genetically Engineered Microbes.

  2025cites this paper
• Streamlined isolation of E. coli biofactory metabolites using centrifugal extraction and partition chromatographic techniques. New hydroxytyrosol derivatives.

  2025cites this paper
• Hydroxytyrosol isolation, comparison of synthetic routes and potential biological activities

  2024influential citation
• Structural and antioxidant properties of hydroxytyrosol-pectin conjugates: Comparative analysis of adsorption and free radical methods and their impact on in vitro gastrointestinal process.

  2024cites this paper
• The Bioactivity of a Hydroxytyrosol-Enriched Extract Originated after Direct Hydrolysis of Olive Leaves from Greek Cultivars

  2024cites this paper
• Efficient production of hydroxytyrosol by directed evolution of HpaB in Escherichia coli.

  2023cites this paper
• Production of hydroxytyrosol from tyrosol via controllable oxidation with immobilized tyrosinase: A comparative study

  2023cites this paper
• Recovery of Hydroxytyrosol from Olive Mill Wastewater Using the Promiscuous Hydrolase/Acyltransferase PestE

  2022cites this paper
• Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives

  2021cites this paper
• Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives

  2021cites this paper
• Photocatalytic Partial Oxidation of Tyrosol: Improving the Selectivity Towards Hydroxytyrosol by Surface Fluorination of TiO2

  2020cites this paper
• Ultrasound‐Assisted Natural Deep Eutectic Solvents as Separation‐Free Extraction Media for Hydroxytyrosol from Olives

  2020cites this paper
• Efficient Synthesis of Hydroxytyrosol from l-3,4-Dihydroxyphenylalanine Using Engineered Escherichia coli Whole Cells.

  2019cites this paper
• Synthetic Evidence of the Amadori-Type Alkylation of Biogenic Amines by the Neurotoxic Metabolite Dopegal

  2019cites this paper
• Phytochemical Investigation of Tradescantia Albiflora and Anti-Inflammatory Butenolide Derivatives

  2019cites this paper
• Synthesis and Study of Hydroxytyrosol Derivatives

  2019cites this paper
• A Three-Step, Gram-Scale Synthesis of Hydroxytyrosol, Hydroxytyrosol Acetate, and 3,4-Dihydroxyphenylglycol

  2019influential citation
• Chemical, physical and biotechnological approaches to the production of the potent antioxidant hydroxytyrosol

  2019influential citation