Thujaplicin

Last updated
Thujaplicin
Identifiers
  • α:1946-74-3 X mark.svgN
  • β:499-44-5 X mark.svgN
  • γ:672-76-4 X mark.svgN
3D model (JSmol)
ChEBI
ChEMBL
EC Number
  • β:207-880-7
PubChem CID
UNII
  • α:InChI=1S/C10H12O2/c1-7(2)8-5-3-4-6-9(11)10(8)12/h3-7H,1-2H3,(H,11,12)
    Key: TUFYVOCKVJOUIR-UHFFFAOYSA-N
  • β:InChI=1S/C10H12O2/c1-7(2)8-4-3-5-9(11)10(12)6-8/h3-7H,1-2H3,(H,11,12)
    Key: FUWUEFKEXZQKKA-UHFFFAOYSA-N
  • γ:InChI=1S/C10H12O2/c1-7(2)8-3-5-9(11)10(12)6-4-8/h3-7H,1-2H3,(H,11,12)
    Key: WKEWHSLZDDZONF-UHFFFAOYSA-N
  • α:CC(C)C1=C(C(=O)C=CC=C1)O
  • β:CC(C)C1=CC(=O)C(=CC=C1)O
  • γ:CC(C)C1=CC=C(C(=O)C=C1)O
Properties
C10H12O2
Molar mass 164.204 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Thujaplicins (isopropyl cycloheptatrienolones) are a series of tropolone-related chemical substances that have been isolated from the hardwoods of the trees of Cupressaceae family. [1] These compounds are known for their antibacterial, antifungal, and antioxidant properties. [2] [3] They were the first natural tropolones to be made synthetically. [4]

Contents

History

Thuja plicata Donn ex D. Don (Western red cedar) - a tree belonging to the Cupressaceae family from which thujaplicins were first purified Thuja plicata Vancouver.jpg
Thuja plicata Donn ex D. Don (Western red cedar) – a tree belonging to the Cupressaceae family from which thujaplicins were first purified

Thujaplicins were discovered in the mid-1930s and purified from the heartwood of Thuja plicata Donn ex D. Don, commonly called as Western red cedar tree. [5] These compounds were also identified in the constituents of Chamaecyparis obtusa , another species from the Cupressaceae family. C. obtusa is native to East Asian countries including Japan and Taiwan, and is also known as Taiwan hinoki, from which the β-thujaplicin was first isolated in 1936 and received its name, hinokitiol. Thujaplicins were the first natural tropolones to be made synthetically, by Ralph Raphael and colleagues, and the β-thujaplicin was the first non-benzenoid aromatic compound identified, by Tetsuo Nozoe and colleagues. [4] [5] The resistance of the heartwood of the tree to decay was the main reason prompting to investigate its content and identify the compounds responsible for antimicrobial properties. [4] β-thujaplicin gained more scientific interest beginning in the 2000s. [6] Later, iron-binding activity of β-thujaplicin was discovered and the molecule has been ironically nicknamed as “Iron Man molecule”, [7] because the first name of Tetsuo Nozoe can be translated into English as “Iron Man”. [6]

Occurrence and isolation

Tjujaplicins are found in the hardwoods of the trees belonging to the Cupressaceae family, including Chamaecyparis obtusa (Hinoki cypress), Thuja plicata (Western red cedar), Thujopsis dolabrata var. hondai (Hinoki asunaro), Juniperus cedrus (Canary Islands juniper), Cedrus atlantica (Atlas cedar), Cupressus lusitanica (Mexican white cedar), Chamaecyparis lawsoniana (Port Orford cedar), Chamaecyparis taiwanensis (Taiwan cypress), Chamaecyparis thyoides (Atlantic white cedar), Cupressus arizonica (Arizona cypress), Cupressus macnabiana (MacNab cypress), Cupressus macrocarpa (Monterey cypress), Juniperus chinensis (Chinese juniper), Juniperus communis (Common juniper), Juniperus californica (California juniper), Juniperus occidentalis (Western juniper), Juniperus oxycedrus (Cade), Juniperus sabina (Savin juniper), Calocedrus decurrens (California incense-cedar), Calocedrus formosana (Taiwan incense-cedar), Platycladus orientalis (Chinese thuja), Thuja occidentalis (Northern white-cedar), Thuja standishii (Japanese thuja), Tetraclinis articulata (Sandarac). [8] [9] [10] [11]

Thujaplicins can be produced in plant cell suspension cultures, [12] [13] or can be extracted from wood using solvents and ultrasonication. [14]

Biosynthesis

Thujaplicins can be synthesized by cycloaddition of isopropylcyclopentadiene and dichloroketene, 1,3-dipolar cycloaddition of 5-isopropyl-1-methyl-3-oxidopyridinium, ring expansion of 2-isopropylcyclohexanone, regiocontrolled hydroxylation of oxyallyl (4+3) cycloadducts, from (R)-(+)-limonene regioselectively by several steps, and from troponeirontricarbonyl complex by few steps. [15] [16] The synthesis pathway of β-thujaplicin from troponeirontricarbonyl complex is found below:

Biosynthesis of beta-thujaplicin from troponeirontricarbonyl complex.svg

The synthesis pathway of β-thujaplicin by electro-reductive alkylation of substituted cycloheptatrienes is shown below:

Biosynthesis of beta-thujaplicin through electroreductive alkylation.svg

The synthesis pathway of β-thujaplicin through ring expansion of 2-isopropylcyclohexanone is shown below:

Biosynthesis of beta-thujaplicin from 2-isopropylcyclohexanone.svg

The synthesis pathway of β-thujaplicin through oxyallyl cation [4+3] cyclization (Noyori's synthesis) is shown below:

Biosynthesis of b-thujaplicin through oxyallyl cation (4+3) cyclization.svg

Chemistry

Thujaplicins belong to tropolones containing an unsaturated seven-membered carbon ring. Thujaplicins are monoterpenoids that are cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at positions 3, 4 or 5. [17] These compounds are enols and cyclic ketones. They derive from a hydride of a cyclohepta-1,3,5-triene. Thujaplicins are soluble in organic solvents and aqueous buffers. Hinokitiol is soluble in ethanol, dimethyl sulfoxide, dimethylformamide with a solubility of 20, 30 and 12.5 mg/ml, respectively. [18] β-thujaplicin provides acetone on vigorous oxidation and gives the saturated monocyclic diol upon catalytic hydrogenation. [19] It is stable to alkali and acids, forming salts or remaining unchanged, but does not convert to catechol derivatives. The complexes made of iron and tropolones display high thermodynamic stability and has shown to have a stronger binding constant than the trnasferrin-iron complex. [20]

There are three naturally occurring monocyclic tropolones described: α-thujaplicin, β-thujaplicin (hinokitiol), and γ-thujaplicin. [4] And the most common isomer occurring in the nature is β-thujaplicin. [21]

CompoundChemical structure3D model of the molecule IUPAC name
α-thujaplicin [22]
Alpha-thujaplicin.png
Alpha-Thujaplicin-3D-balls.png
2-hydroxy-3-propan-2-ylcyclohepta-2,4,6-trien-1-one
β-thujaplicin (hinokitiol) [23]
Beta-thujaplicin.png
Beta-Thujaplicin-3D-balls.png
2-hydroxy-6-propan-2-ylcyclohepta-2,4,6-trien-1-one
γ-thujaplicin [24] 2-hydroxy-5-propan-2-ylcyclohepta-2,4,6-trien-1-one

Biological properties

Antibacterial and antifungal activity

Antiviral activity

Anti-inflammatory activity

Insecticidal and pesticidal activity

Thujaplicins are shown to act against Reticulitermes speratus (Japanese termites), Coptotermes formosanus (super termites), Dermatophagoides farinae (dust mites), Tyrophagus putrescentiae (mould mites), Callosobruchus chinensis (adzuki bean weevil), Lasioderma serricorne (cigarette beetle). [9] [25] [11]

Hinokitiol has also shown some larvicidal activities against Aedes aegypti (yellow fever mosquito) and Culex pipiens (common house mosquito), and anti-plasmodial activities against Plasmodium falciparum and Plasmodium berghei . [11]

Antioxidant activity

Chelating and ionophore activity

Thujaplicins, as other tropolones, demonstrate chelating activity, acting as an ionophore by binding different metal ions. [26]

Anti-browning activity

Tropolone and thujaplicins exhibit potent suppressive activity on enzymatic browning due to inhibition of polyphenol oxidase and tyrosinase. This have been shown in experiments on different vegetables, fruits, mushrooms, plants and other agricultural products. [11] Prevention of darkening has also been elicited on seafood products. [27]

Applications

Skin care and cosmetics

Owing to their antibacterial activities against various microbes colonizing and affecting the skin, thujaplicins are used in skin care and hair growth products, [28] and are especially popular in Eastern Asia.[ citation needed ]

Oral care

Hinokitiol is used in various oral care products, including toothpastes and oral sprays. [28] [29]

Veterinary medicine

Due to its antifungal activity against Malassezia pachydermatis , it is used in eardrop formulations for external otitis in dogs. [30] [31]

Agriculture

Considering their antifungal activity against many plant-pathogenic fungi, and pesticidal and insecticidal properties, the role of thujaplicins in agriculture is evolving, including their use in the management of different plant diseases and for controlling the postharvest decay. [9] [32]

Food additive

Thujaplicins are used as food additives in Japan. [33] Due to its suppressive activity on food browning and the inhibitory activity against bacteria and fungi causing food spoilage (such as Clostridium perfringens , Alternaria alternata , Aspergillus niger , Botrytis cinerea , Fusobacterium species, Monilinia fructicola and Rhizopus stolonifer ), hinokitiol is also used in food packaging as a shelf-life extending agent. [34] [35] [36]

Related Research Articles

Juniper Genus of plants

Junipers are coniferous trees and shrubs in the genus Juniperus of the cypress family Cupressaceae. Depending on taxonomic viewpoint, between 50 and 67 species of junipers are widely distributed throughout the Northern Hemisphere, from the Arctic, south to tropical Africa, from Ziarat, Pakistan, east to eastern Tibet in the Old World, and in the mountains of Central America. The highest-known juniper forest occurs at an altitude of 16,000 ft (4,900 m) in southeastern Tibet and the northern Himalayas, creating one of the highest tree-lines on earth.

<i>Thuja</i> Genus of conifers

Thuja is a genus of coniferous trees in the Cupressaceae. There are five species in the genus, two native to North America and three native to eastern Asia. The genus is monophyletic and sister to Thujopsis. Members are commonly known as arborvitaes, thujas or cedars.

Cypress Index of plants with the same common name

Cypress is a common name for various coniferous trees or shrubs of northern temperate regions that belong to the family Cupressaceae. The word cypress is derived from Old French cipres, which was imported from Latin cypressus, the latinisation of the Greek κυπάρισσος (kyparissos).

Cupressaceae The cypress family of conifers

Cupressaceae is a conifer family, the cypress family, with worldwide distribution. The family includes 27–30 genera, which include the junipers and redwoods, with about 130–140 species in total. They are monoecious, subdioecious or (rarely) dioecious trees and shrubs up to 116 m (381 ft) tall. The bark of mature trees is commonly orange- to red- brown and of stringy texture, often flaking or peeling in vertical strips, but smooth, scaly or hard and square-cracked in some species.

<i>Cupressus nootkatensis</i> Species of conifer

Cupressus nootkatensis is a species of trees in the cypress family native to the coastal regions of northwestern North America. This species goes by many common names including: Nootka cypress, yellow cypress, Alaska cypress, Nootka cedar, yellow cedar, Alaska cedar, and Alaska yellow cedar. The specific epithet "nootkatensis" is derived from its discovery by Europeans on the lands of a First Nation of Canada, those lands of the Nuu-chah-nulth people of Vancouver Island, British Columbia, who were formerly referred to as the Nootka.

<i>Thuja plicata</i> Species of conifer in the family Cupressaceae

Thuja plicata is an evergreen coniferous tree in the cypress family, Cupressaceae, native to western North America. Its common name is western redcedar and it is also called Pacific redcedar, giant arborvitae or western arborvitae, just cedar, giant cedar, or shinglewood,. It is not a true cedar of the genus Cedrus.

Xanthocyparis is a genus of cypresses in the family Cupressaceae. As of August 2021, it has only one species, Xanthocyparis vietnamensis, native to Vietnam and southeast China. It is commonly known as the Vietnamese golden cypress. The Nootka cypress, Cupressus nootkatensis or Callitropsis nootkatensis, was also placed in the genus, but this has been rejected.

Sister Mary Grace Burns Arboretum

The Sister Mary Grace Burns Arboretum, on the campus of Georgian Court University, in Lakewood Township, New Jersey, United States, was once the landscaped park for the winter home of George Jay Gould, millionaire son of railroad tycoon Jay Gould.

Ralph Raphael British chemist

Ralph Alexander Raphael was a British organic chemist, well known for his use of acteylene derivatives in the synthesis of natural products with biological activity.

Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen functionality or missing a methyl group, are called monoterpenoids. Monoterpenes and monoterpenoids are diverse. They have relevance to the pharmaceutical, cosmetic, agricultural, and food industries.

Tropolone Chemical compound

Tropolone is an organic compound with the formula C7H5(OH)O. It is a pale yellow solid that is soluble in organic solvents. The compound has been of interest to research chemists because of its unusual electronic structure and its role as a ligand precursor. Although not usually prepared from tropone, it can be viewed as its derivative with a hydroxyl group in the 2-position.

<i>Callophrys gryneus</i> Species of butterfly

Callophrys gryneus, the juniper hairstreak or olive hairstreak, is a butterfly native to North America. It belongs in the family Lycaenidae.

Hinokitiol Chemical compound

Hinokitiol (β-thujaplicin) is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. It is a tropolone derivative and one of the thujaplicins. Hinokitiol is used in oral and skin care products, and is a food additive used in Japan.

Cinara cupressi, the cypress aphid, is a brownish soft-bodied aphid. It sucks sap from twigs of conifers, and can cause damage to the tree, ranging from discoloring of the affected twig to the death of the tree. This insect appears to have originated in the Middle East and has been increasing its range and is considered to be an invasive species in Africa and Europe. It has been included in the List of the world's 100 worst invasive species.

Cedrol Chemical compound

Cedrol is a sesquiterpene alcohol found in the essential oil of conifers, especially in the genera Cupressus (cypress) and Juniperus (juniper). It has also been identified in Origanum onites, a plant related to oregano. Its main uses are in the chemistry of aroma compounds. It makes up about 19% of cedarwood oil Texas and 15.8% of cedarwood oil Virginia.

Mihrabat Nature Park

Mihrabat Nature Park is a nature park located on the Asian part in Beykoz district of Istanbul Province, Turkey.

Tetsuo Nozoe

Tetsuo Nozoe was a Japanese organic chemist. He is known for the discovery of hinokitiol, a seven-membered aromatic compound, and studying non-benzenoid aromatic compounds.

References

  1. ERDTMAN, HOLGER; GRIPENBERG, JARL (May 1948). "Antibiotic Substances from the Heart Wood of Thuja plicata Don". Nature. 161 (4097): 719. doi:10.1038/161719a0. PMID   18860272. S2CID   4074514.
  2. Chedgy, Russell J.; Lim, Young Woon; Breuil, Colette (May 2009). "Effects of leaching on fungal growth and decay of western redcedar". Canadian Journal of Microbiology. 55 (5): 578–586. doi:10.1139/W08-161. PMID   19483786.
  3. Chedgy, R. (2010). Secondary Metabolites of Western Red Cedar (Thuja plicata). Lambert Academic Publishing. ISBN   978-3-8383-4661-8.
  4. 1 2 3 4 Cook, J. W.; Raphael, R. A.; Scott, A. I. (1951). "149. Tropolones. Part II. The synthesis of α-, β-, and γ-thujaplicins". J. Chem. Soc. 0: 695–698. doi:10.1039/JR9510000695.
  5. 1 2 Nakanishi, Koji (June 2013). "Tetsuo Nozoe's "Autograph Books by Chemists 1953-1994": An Essay". The Chemical Record. 13 (3): 343–352. doi: 10.1002/tcr.201300007 . PMID   23737463.
  6. 1 2 "Hinokitiol". American Chemical Society.
  7. Service, Robert (11 May 2017). "Iron Man molecule restores balance to cells". Science. doi:10.1126/science.aal1178.
  8. Okabe, T; Saito, K (1994). "Antibacterial and preservative effects of natural Hinokitiol (beta-Thujaplicin) extracted from wood". Acta Agriculturae Zhejiangensis. 6 (4): 257–266.
  9. 1 2 3 Morita, Yasuhiro; Matsumura, Eiko; Okabe, Toshihiro; Fukui, Toru; Shibata, Mitsunobu; Sugiura, Masaaki; Ohe, Tatsuhiko; Tsujibo, Hiroshi; Ishida, Nakao; Inamori, Yoshihiko (2004). "Biological Activity of α-Thujaplicin, the Isomer of Hinokitiol". Biological & Pharmaceutical Bulletin. 27 (6): 899–902. doi: 10.1248/bpb.27.899 .
  10. Rebia, Rina Afiani; binti Sadon, Nurul Shaheera; Tanaka, Toshihisa (22 November 2019). "Natural Antibacterial Reagents (Centella, Propolis, and Hinokitiol) Loaded into Poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] Composite Nanofibers for Biomedical Applications". Nanomaterials. 9 (12): 1665. doi: 10.3390/nano9121665 . PMC   6956080 . PMID   31766678.
  11. 1 2 3 4 Saniewski, Marian; Horbowicz, Marcin; Kanlayanarat, Sirichai (10 September 2014). "The Biological Activities of Troponoids and Their Use in Agriculture A Review". Journal of Horticultural Research. 22 (1): 5–19. doi: 10.2478/johr-2014-0001 .
  12. Zhao, J.; Fujita, K.; Yamada, J.; Sakai, K. (1 April 2001). "Improved β-thujaplicin production in Cupressus lusitanica suspension cultures by fungal elicitor and methyl jasmonate". Applied Microbiology and Biotechnology. 55 (3): 301–305. doi:10.1007/s002530000555. PMID   11341310. S2CID   25767209.
  13. Yamada, J.; Fujita, K.; Sakai, K. (April 2003). "Effect of major inorganic nutrients on β-thujaplicin production in a suspension culture of Cupressus lusitanica cells". Journal of Wood Science. 49 (2): 172–175. doi:10.1007/s100860300027. S2CID   8355694.
  14. Chedgy, Russell J.; Daniels, C.R.; Kadla, John; Breuil, Colette (1 March 2007). "Screening fungi tolerant to Western red cedar (Thuja plicata Donn) extractives. Part 1. Mild extraction by ultrasonication and quantification of extractives by reverse-phase HPLC". Holzforschung. 61 (2): 190–194. doi:10.1515/HF.2007.033. S2CID   95994935.
  15. Soung, Min-Gyu; Matsui, Masanao; Kitahara, Takeshi (September 2000). "Regioselective Synthesis of β- and γ-Thujaplicins". Tetrahedron. 56 (39): 7741–7745. doi:10.1016/S0040-4020(00)00690-6.
  16. Liu, Na; Song, Wangze; Schienebeck, Casi M.; Zhang, Min; Tang, Weiping (December 2014). "Synthesis of naturally occurring tropones and tropolones". Tetrahedron. 70 (49): 9281–9305. doi:10.1016/j.tet.2014.07.065. PMC   4228802 .
  17. "2,4,6-Cycloheptatrien-1-one, 2-hydroxy-3-(1-methylethyl)-". pubchem.ncbi.nlm.nih.gov. PubChem.
  18. "Hinokitiol - Product Information" (PDF). www.caymanchem.com. Cayman Chemical.
  19. "Tetsuo Nozoe (1902−1996)". European Journal of Organic Chemistry. 2004 (4): 899–928. February 2004. doi:10.1002/ejoc.200300579.
  20. Hendershott, Lynn; Gentilcore, Rita; Ordway, Frederick; Fletcher, James; Donati, Robert (May 1982). "Tropolone: A lipid solubilizing agent for cationic metals". European Journal of Nuclear Medicine. 7 (5). doi:10.1007/BF00256471.
  21. Bentley, Ronald (2008). "A fresh look at natural tropolonoids". Nat. Prod. Rep. 25 (1): 118–138. doi:10.1039/B711474E.
  22. "2,4,6-Cycloheptatrien-1-one, 2-hydroxy-3-(1-methylethyl)-". pubchem.ncbi.nlm.nih.gov.
  23. "Hinokitiol". pubchem.ncbi.nlm.nih.gov.
  24. "gamma-Thujaplicin". pubchem.ncbi.nlm.nih.gov.
  25. INAMORI, Yoshihiko; SAKAGAMI, Yoshikazu; MORITA, Yasuhiro; SHIBATA, Mistunobu; SUGIURA, Masaaki; KUMEDA, Yuko; OKABE, Toshihiro; TSUJIBO, Hiroshi; ISHIDA, Nakao (2000). "Antifungal Activity of Hinokitiol-Related Compounds on Wood-Rotting Fungi and Their Insecticidal Activities". Biological & Pharmaceutical Bulletin. 23 (8): 995–997. doi: 10.1248/bpb.23.995 .
  26. Pietra, Francesco (August 1973). "Seven-membered conjugated carbo- and heterocyclic compounds and their homoconjugated analogs and metal complexes. Synthesis, biosynthesis, structure, and reactivity". Chemical Reviews. 73 (4): 293–364. doi:10.1021/cr60284a002.
  27. Aladaileh, Saleem; Rodney, Peters; Nair, Sham V.; Raftos, David A. (December 2007). "Characterization of phenoloxidase activity in Sydney rock oysters (Saccostrea glomerata)". Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 148 (4): 470–480. doi:10.1016/j.cbpb.2007.07.089. PMID   17950018.
  28. 1 2 "Hinokitiol | 499-44-5". www.chemicalbook.com.
  29. Suzuki, Joichiro; Tokiwa, Tamami; Mochizuki, Maho; Ebisawa, Masato; Nagano, Takatoshi; Yuasa, Mohei; Kanazashi, Mikimoto; Gomi, Kazuhiro; Arai, Takashi (2008). "Effects of a newly designed toothbrush for the application of periodontal disease treatment medicine (HinoporonTM) on the plaque removal and the improvement of gingivitis". Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology). 50 (1): 30–38. doi: 10.2329/perio.50.030 .
  30. NAKANO, Yasuyuki; MATSUO, Saburo; TANI, Hiroyuki; SASAI, Kazumi; BABA, Eiichiroh (2006). "Therapeutic Effects of β-Thujaplicin Eardrops on Canine Malassezia-Related Otitis Externa". Journal of Veterinary Medical Science. 68 (4): 373–374. doi: 10.1292/jvms.68.373 . PMID   16679729.
  31. NAKANO, Yasuyuki; WADA, Makoto; TANI, Hiroyuki; SASAI, Kazumi; BABA, Eiichiroh (2005). "Effects of β-Thujaplicin on Anti-Malassezia pachydermatis Remedy for Canine Otitis Externa". Journal of Veterinary Medical Science. 67 (12): 1243–1247. doi: 10.1292/jvms.67.1243 . PMID   16397383.
  32. Aharoni, Y.; Copel, A.; Fallik, E. (June 1993). "Hinokitiol (β‐thujaplicin), for postharvest decay control on 'Galia' melons". New Zealand Journal of Crop and Horticultural Science. 21 (2): 165–169. doi: 10.1080/01140671.1993.9513763 .
  33. "The Japan Food chemical Research Faundation". www.ffcr.or.jp.
  34. L. Brody, Aaron; Strupinsky, E. P.; Kline, Lauri R. (2001). Active Packaging for Food Applications (1 ed.). CRC Press. ISBN   9780367397289.
  35. MITSUBOSHI, SAORI; OBITSU, RIE; MURAMATSU, KANAKO; FURUBE, KENTARO; YOSHITAKE, SHIGEHIRO; KIUCHI, KAN (2007). "Growth Inhibitory Effect of Shelf Life Extending Agents on Bacillus subtilis IAM 1026". Biocontrol Science. 12 (2): 71–75. doi: 10.4265/bio.12.71 . PMID   17629249.
  36. Vanitha, Thiraviam; Thammawong, Manasikan; Umehara, Hitomi; Nakamura, Nobutaka; Shiina, Takeo (3 September 2019). "Effect of hinokitiol impregnated sheets on shelf life and quality of "KEK‐1" tomatoes during storage". Packaging Technology and Science. 32 (12): 641–648. doi:10.1002/pts.2479.