289030-99-5

Basic information

• Product Name: Oleocanthal
• Synonyms: Oleocanthal
• CAS NO: 289030-99-5
• Molecular Formula: C₁₇H₂₀O₅
• Molecular Weight: 304.3377
• Mol File: 289030-99-5.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 500.107°C at 760 mmHg
• Flash Point: 180.659°C
• Appearance: /
• Density: 1.165g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.536
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• Stability: Hygroscopic, Unstable in Solution
• CAS DataBase Reference: Oleocanthal(CAS DataBase Reference)
• NIST Chemistry Reference: Oleocanthal(289030-99-5)
• EPA Substance Registry System: Oleocanthal(289030-99-5)

Safety Data

• Hazardous Substances Data: 289030-99-5(Hazardous Substances Data)

Usage

Uses

Oleocanthal is a compound of olive oil with potential use as anti-inflammatory and chemotherapeutic agents.

Definition

ChEBI: A carboxylic ester that is the 2-(p-hydroxyphenyl)ethyl ester of (3S)-4-formyl-3-(2-oxoethyl)hex-4-enoic acid. Oleocanthal is found in olive oil but it is not clear whether the natural product is a mixture of E

InChI:InChI=1/C17H20O5/c1-2-14(12-19)15(7-9-18)11-17(21)22-10-8-13-3-5-16(20)6-4-13/h2-6,9,12,15,20H,7-8,10-11H2,1H3/b14-2-/t15-/m0/s1

Synthetic route

[(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 4-hydroxyphenethyl ester (869476-96-0) → Oleocanthal (289030-99-5)

Conditions	Yield
Stage #1: [(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 4-hydroxyphenethyl ester With hydrogenchloride In acetonitrile Stage #2: With sodium iodite In acetonitrile	75%
Multi-step reaction with 2 steps 1: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 2: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 2 steps 1: HCl / acetonitrile / 1 h / 20 °C 2: 20 mg / NaIO4 / CH2Cl2; H2O / 0 - 20 °C View Scheme

[(1S,3S,4R)-2-Eth-(E)-ylidene-3,4-dihydroxy-cyclopentyl]-acetic acid 2-(4-hydroxy-phenyl)-ethyl ester (944340-53-8) → Oleocanthal (289030-99-5)

Conditions	Yield
With sodium periodate In dichloromethane at 0℃; for 1.25h;	45%
With sodium periodate In dichloromethane; water at 0 - 20℃;	20 mg
With sodium periodate In tetrahydrofuran; water at 0 - 23℃; for 0.75h;	66 mg

(2S,4S,E)-3-ethylidene-4-(2-(4-hydroxyphenethoxy)-2-oxoethyl)-2-{[(2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-3,4dihydro-2H-pyran-5-carboxylic acid → Oleocanthal (289030-99-5)

Conditions	Yield
With β-glucosidase In aq. acetate buffer at 37℃; for 3h; pH=5; Enzymatic reaction;	33%

((3aR,5S,6aR)-2,2-dimethyl-4-oxotetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl)acetic acid methyl ester (869476-93-7) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 2: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 3: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 4: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 5: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 6 steps 1: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 2: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 3: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 4: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 5: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 6: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

[(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid methyl ester (869476-94-8) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 2: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 3: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 4: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 5 steps 1: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 2: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 3: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 4: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 5: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

[(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid (869476-95-9) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 2: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 3: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 4 steps 1: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 2: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 3: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 4: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 3 steps 1: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C 2: HCl / acetonitrile / 1 h / 20 °C 3: 20 mg / NaIO4 / CH2Cl2; H2O / 0 - 20 °C View Scheme

[(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 2-[4-(tert-butyldimethylsilyloxy)phenyl]ethyl ester (951377-85-8) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 2: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 3: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

p-hydroxyphenethyl alcohol (501-94-0) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 2: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 3: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

(3aR,6aR)-2,2-Dimethyl-3a,6a-dihydro-cyclopenta[1,3]dioxol-4-one (115509-13-2) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 7 steps 1: 95 percent / hydrogen / Pd/C / ethyl acetate / 20 °C 2: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 3: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 4: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 5: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 6: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 7: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 8 steps 1: 95 percent / hydrogen / Pd/C / ethyl acetate / 20 °C 2: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 3: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 4: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 5: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 6: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 7: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 8: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

2-(4{[tert-butyl(dimethyl)silyl]oxy}phenyl)ethanol (96013-75-1) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 2: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 3: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 4: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

(4R,5R)-1-(2,2-dimethyl-5-vinyl-[1,3]dioxolan-4-yl)prop-2-en-1-ol (683276-43-9) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: Grubbs catalyst / CH2Cl2 / 4 h / 23 °C 1.2: 87 percent / pyridinium chlorochromate / CH2Cl2 / 12 h / 23 °C 2.1: 95 percent / hydrogen / Pd/C / ethyl acetate / 20 °C 3.1: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 4.1: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 5.1: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 6.1: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 7.1: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 8.1: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 9 steps 1.1: Grubbs catalyst / CH2Cl2 / 4 h / 23 °C 1.2: 87 percent / pyridinium chlorochromate / CH2Cl2 / 12 h / 23 °C 2.1: 95 percent / hydrogen / Pd/C / ethyl acetate / 20 °C 3.1: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 4.1: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 5.1: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 6.1: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 7.1: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 8.1: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 9.1: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

(3aR,6aR)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-one (595581-64-9) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 2: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 3: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 4: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran 5: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 6: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme
Multi-step reaction with 7 steps 1: 57 percent / LHMDS; HMPA; Me2Zn / tetrahydrofuran; toluene / -78 - -45 °C 2: KHMDS; CeCl3 / tetrahydrofuran / -45 °C 3: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 1 h / 20 °C 4: 87 percent / N,N'-dicyclohexylcarbodiimide; 4-dimethylaminopyridine / CH2Cl2 / 0 - 23 °C 5: tetrabutylammonium fluoride; hydrofluoric acid / tetrahydrofuran; H2O / 0 °C / pH 6.5 - 7.0 6: aq. HCl / acetonitrile; H2O / 0.75 h / 23 °C 7: 66 mg / NaIO4 / tetrahydrofuran; H2O / 0.75 h / 0 - 23 °C View Scheme

[(3aS,5S,6aR)-4-Eth-(E)-ylidene-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxol-5-yl]-acetic acid methyl ester → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LiOH / tetrahydrofuran; methanol; H2O / 20 °C 2: 92 percent / triphenylphosphine; diethyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C 3: HCl / acetonitrile / 1 h / 20 °C 4: 20 mg / NaIO4 / CH2Cl2; H2O / 0 - 20 °C View Scheme

C20H26O5 → Oleocanthal (289030-99-5) + (3S,Z)-oleocanthal

Conditions	Yield
Stage #1: C20H26O5 With hydrogenchloride In acetonitrile Stage #2: With sodium periodate

(2S,4S,E)-4-(carboxymethyl)-3-ethylidene-2-{[(2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-3,4-dihydro-2H-pyran-5-carboxylic acid (178600-68-5) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / ethyl acetate / 0 - 20 °C / Inert atmosphere 2: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 3: diethylamine / 20 °C 4: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme
Multi-step reaction with 4 steps 1: pyridine / ethyl acetate / 0 - 20 °C / Inert atmosphere 2: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 3: hydrazine hydrate / ethanol; water / 6 h / 44 °C 4: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme

oleuropeine (32619-42-4) → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide; water / 24 h / 20 °C 2: pyridine / ethyl acetate / 0 - 20 °C / Inert atmosphere 3: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 4: diethylamine / 20 °C 5: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme
Multi-step reaction with 5 steps 1: sodium hydroxide; water / 24 h / 20 °C 2: pyridine / ethyl acetate / 0 - 20 °C / Inert atmosphere 3: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 4: hydrazine hydrate / ethanol; water / 6 h / 44 °C 5: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme

C24H28O14 → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 2: diethylamine / 20 °C 3: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme
Multi-step reaction with 3 steps 1: dmap; triethylamine / 0 - 20 °C / Inert atmosphere 2: hydrazine hydrate / ethanol; water / 6 h / 44 °C 3: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme

C32H38O16 → Oleocanthal (289030-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol; water / 6 h / 44 °C 2: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme
Multi-step reaction with 2 steps 1: diethylamine / 20 °C 2: β-glucosidase / aq. acetate buffer / 3 h / 37 °C / pH 5 / Enzymatic reaction View Scheme

Oleocanthal (289030-99-5) → (3S,4E)-3-(2-hydroxyethyl)-4-hydroxymethylhex-4-enoic acid 2-(4-hydroxyphenyl)ethyl ester (951378-02-2)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0℃; for 0.5h;	97%

Oleocanthal (289030-99-5) → (3S,4E)-4-formyl-3-(2-hydroxyethyl)hex-4-enoic acid 2-(4-hydroxyphenyl)ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / NaBH4 / methanol / 0.5 h / 0 °C 2: 52 percent / MnO2 / tetrahydrofuran / 48 h / 23 °C View Scheme

Oleocanthal (289030-99-5) + N-methoxylamine hydrochloride (593-56-6) → C19H26N2O5 (1273095-02-5)

Conditions	Yield
In methanol at 55℃; for 1h;

Upstream product

• 501-94-0 p-hydroxyphenethyl alcohol 
• 595581-64-9 (3aR,6aR)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-one 
• 683276-43-9 (4R,5R)-1-(2,2-dimethyl-5-vinyl-[1,3]dioxolan-4-yl)prop-2-en-1-ol 
• 96013-75-1 2-(4{[tert-butyl(dimethyl)silyl]oxy}phenyl)ethanol 
• 115509-13-2 (3aR,6aR)-2,2-Dimethyl-3a,6a-dihydro-cyclopenta[1,3]dioxol-4-one 
• 951377-85-8 [(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 2-[4-(tert-butyldimethylsilyloxy)phenyl]ethyl ester 
• 869476-96-0 [(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 4-hydroxyphenethyl ester 
• 869476-95-9 [(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid 
• 869476-94-8 [(3aS,4E,5S,6aR)-4-ethylidene-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]acetic acid methyl ester 
• 869476-93-7 ((3aR,5S,6aR)-2,2-dimethyl-4-oxotetrahydro-3aH-cyclopenta[d][1,3]dioxol-5-yl)acetic acid methyl ester 
• 944340-53-8 [(1S,3S,4R)-2-Eth-(E)-ylidene-3,4-dihydroxy-cyclopentyl]-acetic acid 2-(4-hydroxy-phenyl)-ethyl ester 
• 32619-42-4 oleuropeine 
• 178600-68-5 (2S,4S,E)-4-(carboxymethyl)-3-ethylidene-2-{[(2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-3,4-dihydro-2H-pyran-5-carboxylic acid 

Downstream Products

• 1273095-02-5 C₁₉H₂₆N₂O₅ 
• 951378-02-2 (3S,4E)-3-(2-hydroxyethyl)-4-hydroxymethylhex-4-enoic acid 2-(4-hydroxyphenyl)ethyl ester 

Relevant articles and documents

PROCESS FOR THE PRODUCTION OF OLEOCANTHAL, OLEACEIN AND THEIR ANALOGUES

A process for the production of a compound according to Formula (I), such as oleocanthal or oleacein, starting from oleuropein. The process provides the dialdehyde core of oleocanthal, oleacein and their analogues having the required stereochemistry. Furthermore, the process can be used for the production of a large number of structurally diverse products by varying the structure of the alcohol moiety in the esterification step.

USE OF THE IRRITATING PRINCIPAL OLEOCANTHAL IN OLIVE OIL, AS WELL AS STRUCTURALLY AND FUNCTIONALLY SIMILAR COMPOUNDS

The invention provides oleocanthal analogs and methods of using oleocanthals in various formulations including, food additives; pharmaceuticals; cosmetics; animal repellants; and discovery tools for mammalian irritation receptor genes, gene products, alleles, splice variants, alternate transcripts and the like.

Syntheses of (-)-oleocanthal, a natural NSAID found in extra virgin olive oil, the (-)-deacetoxy-oleuropein aglycone, and related analogues

(Chemical Equation Presented) Phenolic compounds extracted from extra virgin olive oil have attracted considerable recent attention. One of the components, (-)-oleocanthal (1), an inhibitor of the COX-1 and COX-2 enzymes, possesses similar potency as the NSAID ibuprofen. In this, a full account, we disclose the first- and now second-generation syntheses of both enantiomers of the oleocanthals, as well as the first synthesis of the closely related (-)-deacetoxy-oleuropein aglycone and a series of related analogues for structure activity studies. To demonstrate the utility of the second-generation synthesis, multigram quantities of (-)-oleocanthal were prepared in 10 steps (14% overall yield) from commercially available D-lyxose.