Phytol

Phytol
	Phytol
Names
	IUPAC name (5R,9R)-5,6,7,8,9,10,11,12-Octahydro-1,6-secoretinol
	Systematic IUPAC name (2E,7R,11R)-3,7,11,15-Tetramethylhexadec-2-en-1-ol
Identifiers
CAS Number	150-86-7 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:17327 ;
ChEMBL	ChEMBL3039479 ;
ChemSpider	4444094 ;
ECHA InfoCard	100.131.435
PubChem CID	5280435;
UNII	5BC2RZ81NG ;
CompTox Dashboard (EPA)	DTXSID1040586 ;
	InChI InChI=1S/C20H40O/c1-17(2)9-6-10-18(3)11-7-12-19(4)13-8-14-20(5)15-16-21/h15,17-19,21H,6-14,16H2,1-5H3/b20-15+/t18-,19-/m1/s1 Key: BOTWFXYSPFMFNR-PYDDKJGSSA-N ; InChI=1/C20H40O/c1-17(2)9-6-10-18(3)11-7-12-19(4)13-8-14-20(5)15-16-21/h15,17-19,21H,6-14,16H2,1-5H3/b20-15+/t18-,19-/m1/s1 Key: BOTWFXYSPFMFNR-PYDDKJGSBV;
	SMILES C[C@@H](CCC[C@@H](C)CCC/C(=C/CO)/C)CCCC(C)C;
Properties
Chemical formula	C20H40O
Molar mass	296.539 g·mol−1
Density	0.850 g cm−3
Boiling point	203 to 204 °C (397 to 399 °F; 476 to 477 K) at 10 mmHg
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Phytol (florasol, phytosol) is an acyclic hydrogenated diterpene alcohol that is used as a precursor for the manufacture of synthetic forms of vitamin E^[1] and vitamin K1,^[2] as well as in the fragrance industry. Its other commercial uses include cosmetics, shampoos, toilet soaps, and detergents,^[3] as well as in some cannabis distillates as a diluent or for flavoring.^[4] It smells grassy and dominates the aroma of certain green teas.^[5]

Its worldwide use has been estimated to be approximately 0.1–1.0 metric tons per year.^[6]

Pharmacology

Humans

Refsum disease (also known as adult Refsum disease) is an autosomal recessive disorder that results in the accumulation of toxic stores of phytanic acid in tissues and frequently manifests as a variable combination of peripheral polyneuropathy, cerebellar ataxia, retinitis pigmentosa, anosmia, and hearing loss.^[7] Although humans cannot derive phytanic acid from chlorophyll, they can convert free phytol into phytanic acid. Thus, patients with Refsum disease should limit their intake of phytanic acid and free phytol.^[8] The amount of free phytol in numerous food products has been reported.^[9]

Rats

Phytol was found to cause pulmonary hemorrhage and necrosis of nose, throat and lung tissue when exposed in aerosol to Sprague Dawley rats, with no safe dose range being established. A majority of the phytol rats turned out dead or moribund, leading to 2nd-day termination of the 14-day study.^[10]

Other vertebrates

In ruminants, the gut fermentation of ingested plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats.^[11] In shark liver it yields pristane.

History

Controversy

In 2020, Tokyo Smoke, a Canadian cannabis company owned by Canopy Growth at the time; pulled every phytol-containing product from their shelves and issued a 48 hour deadline to suppliers, demanding 'written confirmation' if it was included. A year later, David Heldreth, a former CSO of True Terpenes, a company that still listed it as a product; along with Andrew Freedman, investigated the matter, filing a request under the Access to Information Act to unredact the study causing the product removals.^[12] In the same year, the Canadian government published an amendment to Canadian cannabis regulations regarding "flavours in cannabis extracts".^[13]

Roles in nature

Insects, such as the sumac flea beetle, are reported to use phytol and its metabolites (e.g. phytanic acid) as chemical deterrents against predation.^[14] These compounds originate from host plants.

Indirect evidence has been provided that, in contrast to humans, diverse non-human primates can derive significant amounts of phytol from the hindgut fermentation of plant materials.^[15]^[16]

Modulator of transcription

Phytol and/or its metabolites have been reported to bind to and/or activate the transcription factors PPAR-alpha^[17] and retinoid X receptor (RXR).^[18] The metabolites phytanic acid and pristanic acid are naturally occurring ligands.^[19] In mice, oral phytol induces massive proliferation of peroxisomes in several organs.^[20]

Possible biomedical applications

Phytol has been investigated for its potential anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects.^[21]

Geochemical biomarker

Phytol is likely the most abundant acyclic isoprenoid compound present in the biosphere and its degradation products have been used as biogeochemical tracers in aquatic environments.^[22]

References

^ Netscher, Thomas (2007). "Synthesis of Vitamin E". In Litwack, Gerald (ed.). Vitamin E. Vitamins & Hormones. Vol. 76. pp. 155–202. doi:10.1016/S0083-6729(07)76007-7. ISBN 978-0-12-373592-8. PMID 17628175.
^ Daines, Alison; Payne, Richard; Humphries, Mark; Abell, Andrew (2003). "The Synthesis of Naturally Occurring Vitamin K and Vitamin K Analogues" (PDF). Current Organic Chemistry. 7 (16): 1625–34. doi:10.2174/1385272033486279.
^ McGinty, D.; Letizia, C.S.; Api, A.M. (2010). "Fragrance material review on phytol". Food and Chemical Toxicology. 48: S59–63. doi:10.1016/j.fct.2009.11.012. PMID 20141879.
^ "• Winberry Farms". Archived from the original on 2021-07-21. Retrieved 2019-11-09.
^ "Analysis of volatile aroma compounds..."^{[permanent dead link]}
^ IFRA (International Fragrance Association), 2004. Use Level Survey, August 2004.
^ Wierzbicki, A.S. (2007). "Peroxisomal disorders affecting phytanic acid α-oxidation: A review". Biochemical Society Transactions. 35 (5): 881–6. doi:10.1042/BST0350881. PMID 17956237.
^ Komen, J.C.; Wanders, R.J.A. (2007). "Peroxisomes, Refsum's disease and the α- and ω-oxidation of phytanic acid". Biochemical Society Transactions. 35 (5): 865–9. doi:10.1042/BST0350865. PMID 17956234. S2CID 39842405.
^ Brown, P. June; Mei, Guam; Gibberd, F. B.; Burston, D.; Mayne, P. D.; McClinchy, Jane E.; Sidey, Margaret (1993). "Diet and Refsum's disease. The determination of phytanic acid and phytol in certain foods and the application of this knowledge to the choice of suitable convenience foods for patients with Refsum's disease". Journal of Human Nutrition and Dietetics. 6 (4): 295–305. doi:10.1111/j.1365-277X.1993.tb00375.x.
^ Schwotzer, Daniela; Gigliotti, Andrew; Irshad, Hammad; Dye, Wendy; McDonald, Jacob (January 2021). "Phytol, not propylene glycol, causes severe pulmonary injury after inhalation dosing in Sprague-Dawley rats". Inhalation Toxicology. 33 (1): 33–40. Bibcode:2021InhTx..33...33S. doi:10.1080/08958378.2020.1867260. PMID 33441006.
^ Van Den Brink, D. M.; Wanders, R. J. A. (2006). "Phytanic acid: Production from phytol, its breakdown and role in human disease". Cellular and Molecular Life Sciences. 63 (15): 1752–65. doi:10.1007/s00018-005-5463-y. PMC 11136310. PMID 16799769. S2CID 9186973.
^ Brown, David (19 July 2021). "Study looking at vape pen ingredient phytol shows serious health concerns". StratCann. Retrieved 29 May 2023.
^ "Canada Gazette, Part 1, Volume 155, Number 25". canadagazette.gc.ca. Government of Canada. 19 June 2021. Retrieved 29 May 2023.
^ Vencl, Fredric V.; Morton, Timothy C. (1998). "The shield defense of the sumac flea beetle, Blepharida rhois (Chrysomelidae: Alticinae)". Chemoecology. 8 (1): 25–32. Bibcode:1998Checo...8...25V. doi:10.1007/PL00001800. S2CID 25886345.
^ Watkins, Paul A; Moser, Ann B; Toomer, Cicely B; Steinberg, Steven J; Moser, Hugo W; Karaman, Mazen W; Ramaswamy, Krishna; Siegmund, Kimberly D; Lee, D Rick; Ely, John J; Ryder, Oliver A; Hacia, Joseph G (2010). "Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions". BMC Physiology. 10 19. doi:10.1186/1472-6793-10-19. PMC 2964658. PMID 20932325.
^ Moser, Ann B; Hey, Jody; Dranchak, Patricia K; Karaman, Mazen W; Zhao, Junsong; Cox, Laura A; Ryder, Oliver A; Hacia, Joseph G (2013). "Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells". Lipids in Health and Disease. 12 10. doi:10.1186/1476-511X-12-10. PMC 3571895. PMID 23379307.
^ Gloerich, J.; Van Vlies, N; Jansen, G. A.; Denis, S; Ruiter, J. P.; Van Werkhoven, M. A.; Duran, M; Vaz, F. M.; Wanders, R. J.; Ferdinandusse, S (2005). "A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPAR -dependent and -independent pathways". The Journal of Lipid Research. 46 (4): 716–26. doi:10.1194/jlr.M400337-JLR200. PMID 15654129.
^ Kitareewan, S.; Burka, L. T.; Tomer, K. B.; Parker, C. E.; Deterding, L. J.; Stevens, R. D.; Forman, B. M.; Mais, D. E.; Heyman, R. A.; McMorris, T.; Weinberger, C. (1996). "Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR". Molecular Biology of the Cell. 7 (8): 1153–66. doi:10.1091/mbc.7.8.1153. PMC 275969. PMID 8856661.
^ Zomer, Anna W.M.; Van Der Saag, Paul T.; Poll-The, Bwee Tien (2003). "Phytanic and Pristanic Acid Are Naturally Occuring [sic] Ligands". In Roels, Frank; Baes, Myriam; De Bie, Sylvia (eds.). Peroxisomal Disorders and Regulation of Genes. Advances in Experimental Medicine and Biology. Vol. 544. pp. 247–54. doi:10.1007/978-1-4419-9072-3_32. ISBN 978-1-4613-4782-8. PMID 14713238.
^ Van Den Branden, Christiane; Vamecq, Joseph; Wybo, Ingrid; Roels, Frank (1986). "Phytol and Peroxisome Proliferation". Pediatric Research. 20 (5): 411–5. doi:10.1203/00006450-198605000-00007. PMID 2423950.
^ Islam, MT; Ali, ES; Uddin, SJ; Shaw, S; Islam, MA; Ahmed, MI; Chandra Shill, M; Karmakar, UK; Yarla, NS; Khan, IN; Billah, MM; Pieczynska, MD; Zengin, G; Malainer, C; Nicoletti, F; Gulei, D; Berindan-Neagoe, I; Apostolov, A; Banach, M; Yeung, AWK; El-Demerdash, A; Xiao, J; Dey, P; Yele, S; Jóźwik, A; Strzałkowska, N; Marchewka, J; Rengasamy, KRR; Horbańczuk, J; Kamal, MA; Mubarak, MS; Mishra, SK; Shilpi, JA; Atanasov, AG (November 2018). "Phytol: A review of biomedical activities". Food and Chemical Toxicology. 121: 82–94. doi:10.1016/j.fct.2018.08.032. hdl:2328/39143. PMID 30130593. S2CID 52055348.
^ Rontani, Jean-François; Volkman, John K. (2003). "Phytol degradation products as biogeochemical tracers in aquatic environments". Organic Geochemistry. 34 (1): 1–35. Bibcode:2003OrGeo..34....1R. doi:10.1016/S0146-6380(02)00185-7.