Nootkatone

Structural formula
General
Surname	Nootkatone
other names	(4 R , 4a S , 6 R ) -6-Isopropenyl-4,4a-dimethyl-4,4a, 5,6,7,8-hexahydro-2 (3 H ) -naphthalenone ( IUPAC ) ; 4α, 5-dimethyl-1,2,3,4,4α, 5,6,7-octahydro-7-keto-3-isopropenylnaphthalene; (+) - nootkatone; NOOTKATONE ( INCI )
Molecular formula	C 15 H 22 O
Brief description	colorless solid
External identifiers / databases
EC number	225-124-4
ECHA InfoCard	100.022.840
PubChem	1268142
ChemSpider	1064812
Wikidata	Q417896
properties
Molar mass	218.55 g mol −1
Physical state	firmly
density	1.00 g cm −3
Melting point	32-33 ° C ; 36–37 ° C ((+) - Nootkaton);
boiling point	125 ° C (at 67 Pa )
Vapor pressure	approx. <0.001 hPa at 25 ° C
solubility	practically insoluble in water
safety instructions
GHS labeling of hazardous substances Caution
H and P phrases	H: 317
	P: 280
Toxicological data	> 5000 mg kg −1 ( LD 50 , rat , oral ) ; > 5000 mg kg −1 ( LD 50 , rabbit , skin ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nootkatone is a bicyclic sesquiterpene and occurs as a specific aroma in many types of citrus. Natural nootkatone is a high-priced natural flavoring agent and is mainly used as a flavoring agent in soft drinks and as a pharmaceutical. Isolation from natural sources is very expensive, as the content of this substance is only around 0.01% in mandarin and orange oil and around 0.5% in grapefruit oil.

properties

Grapefruit, here with red pulp

Grapefruit with yellow pulp

Nootkaton is a crystalline, colorless solid, above the melting point of 32 to 33 ° C a viscous, yellow liquid. The molecule has three stereogenic centers. The two enantiomers differ greatly in their aroma intensity and aroma property:

(+) - Nootkaton is the odor carrier of grapefruit; the odor threshold is 0.001 ppm and the taste is bitter.
(-) - Nootkatone has a woody odor; the odor threshold is 1 ppm.

The market price for natural (+) - nootkatone is between 4,000 and 6,500 € / kg.

Technical production of nootkatone from valencene

There are several methods of making nootkatone. Most start from the bicyclic sesquiterpene (+) valencene , which is the main component of the essential oil of the Valencia orange and grapefruit (in addition to limonene , myrcene and linalool and other terpenoid secondary components). Valencene is cheap and available in large quantities.

Chemical process

Photooxygenation in the presence of copper salts
Metal catalytic transformation
Oxidation with tert -Butylperacetat or tert -Butylchromat , butyl chromate and valencene
Synthesis from cyclohexene or cyclohexadiene derivatives

Biotechnological processes

In contrast to the nootkatone produced with chemical processes, the biotechnologically produced nootkatone can be described as natural and can therefore also be used as a natural flavoring substance.

These processes include whole-cell biotransformation

Fungi such as Chaetomium globosum , Pleurotus sapidus , Botryosphaeria rhodina , Phanerochaete chrysosporim , Botryosphaeria dothide , Trametes spec.
Bacteria such as Enterobacter sp. , Rodococcus KSM-5706
Plants such as Gynostemma pentaphyllum

Nootkatone can also be synthesized using other biotechnological processes:

Enzymatic processes (isolated enzyme)
Laccase e.g. B. from Trametes versicolor
Lignin peroxidase
P450 monooxygenases

use

In addition to its main use as a flavoring agent for beverages, it can be used as an insect repellent and as a ripening indicator.

Individual evidence

↑ entry to nootkatone in CosIng database of the European Commission, accessed on 4 March 2020th
↑ ^a ^b ^c ^d ^e ^f ^g data sheet (+) - Nootkatone at Sigma-Aldrich , accessed on April 16, 2017 ( PDF ).
↑ ^a ^b ^c Data sheet Nootkatone at AlfaAesar, accessed on March 23, 2010 ( PDF )(JavaScript required) .
↑ ^a ^b ^c ^d ^e Entry on (+) - Nootkaton. In: Römpp Online . Georg Thieme Verlag, accessed on July 12, 2014.
↑ Wolfgang Legrum: Fragrances, between stench and fragrance - occurrence, properties and use of fragrances and their mixtures . 2nd revised and expanded edition. Springer Spectrum, 2015, ISBN 978-3-658-07309-1 , pp. 37 .
↑ Nachr. Chem. Techn. 19 (24), (1971).
↑ ^a ^b H. Willershausen, Chemiker-Zeitung , 115 (12), (1991.)
^ Charles W. Wilson III, Philip E. Shaw: Synthesis of nootkatone from valencene . In: Journal of Agricultural and Food Chemistry . tape 26 , no. 6 , November 1978, p. 1430-1432 , doi : 10.1021 / jf60220a054 .
↑ GLK Hunter, WB Brogden Jr .: Conversion of Valencene to Nootkatone . In: Journal of Food Science . tape 30 , no. 5 , September 1965, p. 876-878 , doi : 10.1111 / j.1365-2621.1965.tb01858.x .
↑ AJ Birch: Dihydrobenzenes in Synthesis in Terpene Related Areas . In: Journal of Agricultural and Food Chemistry . tape 22 , no. 2 , March 1974, p. 162-167 , doi : 10.1021 / jf60192a049 .
↑ Rüdiger Kaspera: Oxyfunctionalization of terpene hydrocarbons to aroma-active terpenoids by selective biocatalysis . Hanover 2004, DNB 971240833 , urn : nbn: de: gbv: 089-3797690931 (dissertation, University of Hanover).
↑ ^a ^b Mai Furusawa, Toshihiro Hashimoto, Yoshiaki Noma, Yoshinori Asakawa: Biotransformation of Citrus Aromatics Nootkatone and Valencene by Microorganisms . In: Chemical and Pharmaceutical Bulletin . tape 53 , no. January 11 , 2005, p. 1423-1429 , doi : 10.1248 / cpb.53.1423 .

↑ Janssens, L .; Proc. Biochem., 27, (1992).

↑ Rüdiger Kaspera, Ulrich Krings, Tsevegsuren Nanzad, Ralf G. Berger: bioconversion of (+) - valencene in submerged cultures of the ascomycete Chaetomium globosum . In: Applied Microbiology and Biotechnology . tape 67 , no. 4 , June 2005, p. 477-483 , doi : 10.1007 / s00253-004-1794-0 .

↑ Hiroshi Sakamakia, Ken-ichi Itoha, Tetsuyuki Taniaib, Susumu Kitanakac, Yoshikazu Takagid, Wen Chaie, C. Akira Horiuchie: Biotransformation of valencene by cultured cells of Gynostemma pentaphyllum . In: Journal of Molecular Catalysis B : Enzymatic . tape 32 , no. 3 , January 2005, p. 103-106 , doi : 10.1016 / j.molcatb.2004.10.004 .

↑ Patent US6200786 : Process for the preparation of nootkatone by laccase catalysis. Published March 13, 2001 , Inventors: Rongmin Huang, Philip A. Christenson, Ivica Labuda. ‌

↑ H. Willershausen, CLB Chem Labor Biotechnol, 47, (2002).

↑ Rebecca J. Sowden, Samina Yasmin, Nicholas H. Rees, Stephen G. Bell, Luet-Lok Wong: Biotransformation of the sesquiterpene (+) - valencene by cytochrome P450cam and P450BM-3 . In: Organic and Biomolecular Chemistry . tape 3 , no. 1 , December 2005, p. 57-64 , doi : 10.1039 / B413068E .

↑ Mitsuo Miyazawa, Yuji Nakamura, Yukio Ishikawa: Insecticidal Sesquiterpene from Alpinia oxyphylla against Drosophila melanogaster . In: Journal of Agricultural and Food Chemistry . tape 48 , no. 8 , August 2000, p. 3639-3641 , doi : 10.1021 / jf000325z .

↑ Andrea Biolatto, Ana M. Sancho, Rodolfo JC Cantet, Daniel R. Güemes, Norma A. Pensel: Use of Nootkatone as a Senescence Indicator for Rouge La Toma Cv. Grapefruit (Citrus paradisi Macf.) . In: Journal of Agricultural and Food Chemistry . tape 50 , no. 17 , August 2002, p. 4816-4819 , doi : 10.1021 / jf011674b .

[CosIng-1] try to nootkatone in CosIng database of the European Commission, accessed on 4 March 2020th

[SIGMA-2] ↑ ^a ^b ^c ^d ^e ^f ^g data sheet (+) - Nootkatone at Sigma-Aldrich , accessed on April 16, 2017 ( PDF ).

[alpha-3] Data sheet Nootkatone at AlfaAesar, accessed on March 23, 2010 ( PDF )(JavaScript required) .

[Roempp-4] Entry on (+) - Nootkaton. In: Römpp Online . Georg Thieme Verlag, accessed on July 12, 2014.

[Legrum-5] Wolfgang Legrum: Fragrances, between stench and fragrance - occurrence, properties and use of fragrances and their mixtures . 2nd revised and expanded edition. Springer Spectrum, 2015, ISBN 978-3-658-07309-1 , pp. 37 .

[6] Nachr. Chem. Techn. 19 (24), (1971).

[Willershausen-7] H. Willershausen, Chemiker-Zeitung , 115 (12), (1991.)

[8] Charles W. Wilson III, Philip E. Shaw: Synthesis of nootkatone from valencene . In: Journal of Agricultural and Food Chemistry . tape 26 , no. 6 , November 1978, p. 1430-1432 , doi : 10.1021 / jf60220a054 .

[9] GLK Hunter, WB Brogden Jr .: Conversion of Valencene to Nootkatone . In: Journal of Food Science . tape 30 , no. 5 , September 1965, p. 876-878 , doi : 10.1111 / j.1365-2621.1965.tb01858.x .

[10] AJ Birch: Dihydrobenzenes in Synthesis in Terpene Related Areas . In: Journal of Agricultural and Food Chemistry . tape 22 , no. 2 , March 1974, p. 162-167 , doi : 10.1021 / jf60192a049 .

[11] Rüdiger Kaspera: Oxyfunctionalization of terpene hydrocarbons to aroma-active terpenoids by selective biocatalysis . Hanover 2004, DNB 971240833 , urn : nbn: de: gbv: 089-3797690931 (dissertation, University of Hanover).

[Furusawa-12] Mai Furusawa, Toshihiro Hashimoto, Yoshiaki Noma, Yoshinori Asakawa: Biotransformation of Citrus Aromatics Nootkatone and Valencene by Microorganisms . In: Chemical and Pharmaceutical Bulletin . tape 53 , no. January 11 , 2005, p. 1423-1429 , doi : 10.1248 / cpb.53.1423 .

[13] Janssens, L .; Proc. Biochem., 27, (1992).

[14] Rüdiger Kaspera, Ulrich Krings, Tsevegsuren Nanzad, Ralf G. Berger: bioconversion of (+) - valencene in submerged cultures of the ascomycete Chaetomium globosum . In: Applied Microbiology and Biotechnology . tape 67 , no. 4 , June 2005, p. 477-483 , doi : 10.1007 / s00253-004-1794-0 .

[15] Hiroshi Sakamakia, Ken-ichi Itoha, Tetsuyuki Taniaib, Susumu Kitanakac, Yoshikazu Takagid, Wen Chaie, C. Akira Horiuchie: Biotransformation of valencene by cultured cells of Gynostemma pentaphyllum . In: Journal of Molecular Catalysis B : Enzymatic . tape 32 , no. 3 , January 2005, p. 103-106 , doi : 10.1016 / j.molcatb.2004.10.004 .

[16] Patent US6200786 : Process for the preparation of nootkatone by laccase catalysis. Published March 13, 2001 , Inventors: Rongmin Huang, Philip A. Christenson, Ivica Labuda. ‌

[17] H. Willershausen, CLB Chem Labor Biotechnol, 47, (2002).

[18] Rebecca J. Sowden, Samina Yasmin, Nicholas H. Rees, Stephen G. Bell, Luet-Lok Wong: Biotransformation of the sesquiterpene (+) - valencene by cytochrome P450cam and P450BM-3 . In: Organic and Biomolecular Chemistry . tape 3 , no. 1 , December 2005, p. 57-64 , doi : 10.1039 / B413068E .

[19] Mitsuo Miyazawa, Yuji Nakamura, Yukio Ishikawa: Insecticidal Sesquiterpene from Alpinia oxyphylla against Drosophila melanogaster . In: Journal of Agricultural and Food Chemistry . tape 48 , no. 8 , August 2000, p. 3639-3641 , doi : 10.1021 / jf000325z .

[20] Andrea Biolatto, Ana M. Sancho, Rodolfo JC Cantet, Daniel R. Güemes, Norma A. Pensel: Use of Nootkatone as a Senescence Indicator for Rouge La Toma Cv. Grapefruit (Citrus paradisi Macf.) . In: Journal of Agricultural and Food Chemistry . tape 50 , no. 17 , August 2002, p. 4816-4819 , doi : 10.1021 / jf011674b .