Nootkatone has a pleasant taste. It may be prepared by oxidation of valencene (a sesquiterpene) with tertiary butyl chromate.
(+)-Nootkatone is sesquiterpene ketone originally isolated from grapefruit juice and peel oil with diverse biological activity. It is lethal against ticks, fleas, and mosquitoes with LC50 values of 0.0029, 0.0061, and 0.0046% w/v, respectively. Pretreatment of wood with (+)-nootkatone reduces tunnel lengths, feeding, and survival rates in C. formosanus termites. (+)-Nootkatone (10-100 μM) dose-dependently activates AMPKα1 and AMPKα2 in C2C12 mouse myoblast lysate containing a substrate peptide. It dose-dependently inhibits platelet aggregation induced by collagen, thrombin , and arachidonic acid when used at concentrations ranging from 10 to 100 μM with almost complete inhibition at the highest concentration. In vivo, (+)-nootkatone (3-30 mg/kg, p.o.) dose-dependently increases the length of tail bleeding time in mice. (+)-Nootkatone (0.1-0.3%, p.o.) dose-dependently reduces body weight and plasma glucose levels in mice fed a high-fat and high-sucrose diet.
NOOTKATONE has been isolated from grapefruit peel and juice
and identified in other citrus oils as well. The commercially available product is a
colorless to yellowish liquid with a typical grapefruit odor.
Nootkatone can be prepared by oxidation of valencene, a sesquiterpene hydrocarbon
isolated from orange oils. The oxidation can be accomplished either by
chemical or by biotechnological methods.
Nootkatone is used for flavoring beverages.
viscous yellow liquid or crystals with a citrus odour;
Nootkatone has a powerful fruity sweet, citrusy, grapefruit peel oil-like aroma.
Reported found in grapefruit oil and juice; traces are also reported found in the oils of bergamot, lemon, lime,
orange and tangerine; also reported formed in canned orange juice on storage.
Nootkatone is an effective repellent/insecticide against mosquitos, and may repel bed bugs, head lice and other insects. Nootkatone in spray form has been shown as an effective repellent/insecticide against deer ticks and lone star ticks.
By oxidation of valencene (a sesquiterpene) with tertiary butyl chromate.
ChEBI: A sesquiterpenoid that is 4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one which is substituted by methyl groups at positions 4 and 4a, and by an isopropenyl group at position 6 (the 4R,4aS,6R
stereoisomer).
Detection: 170 to 800 ppb
Taste characteristics at 20 ppm: grapefruit, citrus, orange and butter.
(+)-nootkatone, a bicyclic conjugated sesquiterpene ketone with a grapefruit-like flavor, is commonly used in fragrance, food, cosmetics and pharmaceutical industry. It can be synthesized from (+)-valencene via biotransformation. (+)-nootkatone is the active ingredient responsible for the antiplatelet effect of Cyperus rotundus, a well-known oriental traditional medicine. It also shows promising efficacy against Staphylococcus aureus biofilms.
General procedure for the synthesis of nootkatone (compound 9) from compound (CAS: 72453-44-2): sodium acetate trihydrate (0.22 g, 1.6 mmol) was added to a single necked round bottomed flask equipped with a reflux condenser. Chloroenone compound 8 (0.14 g, 0.54 mmol) was dissolved in glacial acetic acid (4 mL) and the solution was injected into the flask. The mixture was heated to 100 °C and kept at this temperature for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into cold water and extracted with chloroform. The organic layer was washed sequentially with 2% aqueous KOH solution, 2N HCl, NaHCO3 solution and brine and then dried with MgSO4. Excess solvent was removed by rotary evaporator to give Nootkatone as a yellow oil in 93% yield. The total yield of pathway b (from β-pinene to Nootkatone) was 23% and that of pathway a was 25%, both showing higher yields. The enantiomeric purity of the final product was almost unchanged from that of the starting material, β-pinene, due to the fact that both the Oxy-Cope reaction and the methylation step preserve the enantiomeric purity. Qualitative analysis showed that the aroma of the synthesized Nootkatone was consistent with that of Nootkatone from other sources. Its 1H NMR data (250 MHz, CDCl3) were in agreement with literature reports: δ 5.77 (s, 1H), 4.75-4.72 (m, 2H), 2.62-2.43 (m, 1H), 2.41-2.22 (m, 4H), 2.09-1.87 (m, 3H), 1.46-1.38 (m, 1H), 1.12- 1.10 (m, 4H), 0.98 (d, 3H). In addition, the use of quaternary ammonium compounds, polyethylene glycol (PEG), or tris[2-(2-methoxyethoxy)ethyl]amine, etc., instead of 18-crown-6 as phase transfer catalysts or metal chelating agents, may be considered in the Oxy-Cope reaction to reduce the cost.
[1] Patent: US7112700, 2006, B1. Location in patent: Page/Page column 7; 1/3
[2] Organic Letters, 2009, vol. 11, # 16, p. 3530 - 3533
[3] Patent: WO2017/100437, 2017, A1. Location in patent: Paragraph 00034; 00035
[4] Journal of Organic Chemistry, 1982, vol. 47, # 24, p. 4622 - 4626
