Login Register Cart 0
Generic placeholder image

Recent Advances in Anti-Infective Drug Discovery

Editor-in-Chief

ISSN (Print): 2772-4344
ISSN (Online): 2772-4352

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Pulegone: An Emerging Oxygenated Cyclic Monoterpene Ketone Scaffold Delineating Synthesis, Chemical Reactivity, and Biological potential

Author(s): Ashwani K. Dhingra and Bhawna Chopra*

Volume 18, Issue 1, 2023

Published on: 10 November, 2022

Page: [16 - 28] Pages: 13

DOI: 10.2174/2772434418666221018090507

Price: $65

conference banner
Abstract

Pulegone ((R)-5-Methyl-2-(1-methylethylidine) cyclohexanone) is a pharmacologically active, natural monoterpene ketone obtained from leaves and flowering tops of the mint family (Lamiaceae). The aim is to comprise the physicochemical and biological aspects of pulegone. All significant databases were collected via electronic search using Pubmed, Scopus, Web of Science, and Science Direct and were compiled. This review presents the occurrence, chemistry, and modifications of pulegone structure and its effect on the biological system. Pulegone represents various pharmacological properties, i.e., antioxidant, antimicrobial, anti-feeding, antifungal, antiviral, and pesticide activities, and has a significant role as an abortifacient and emmenagogue. Thus, this present review concludes the knowledgeable erudition on pulegone that paves the way for further work.

« Previous Next »
Graphical Abstract

[1]
Chalchat JC, Garry RP, Muhayimana A. Essential oil of Tagetes minuta from Rwanda and France: Chemical composition according to harvesting location, growth stage and part of plant extracted. J Essent Oil Res 1995; 7(4): 375-86.
[http://dx.doi.org/10.1080/10412905.1995.9698544]
[2]
Senatore F, Napolitano F, Mohamed M, Harris PJC, Mnkeni PNS, Henderson J. Antibacterial activity of Tagetesminuta L. (Asteraceae) essential oil with different chemical composition. J Flavour Fragr 2004; 19(6): 574-8.
[3]
Weaver DK, Wells CD, Dunkel FV, Bertsch W, Sing SE, Sriharan S. Insecticidal activity of floral, foliar, and root extracts of Tagetes minuta (Asterales: Asteraceae) against adult Mexican bean weevils (Coleoptera: Bruchidae). J Econ Entomol 1994; 87(6): 1718-25.
[http://dx.doi.org/10.1093/jee/87.6.1718]
[4]
You-Ping Z. Chinese materia medica: Chemistry, Pharmacology and Applications Autralia. Harwood Academic Publishers 1998.
[5]
Walton NJ, Brown DE. Chemicals from Plants: Perspectives on Plant Secondary Products. London: Imperial College Press 1999.
[http://dx.doi.org/10.1142/3203]
[6]
Rees A. Tagetes. The Cyclopedia London 1817; p. 35.
[7]
Teisseire PJ. Chemistry of Fragrant Substances. New York: VCH 1994; pp. 396-7.
[8]
Hidetaka T. Preparation of dihydrotagetone from methacrolienacetal as raw material Japan Patent JP58170726A2 1983.
[9]
Le Borgne JF, Cuvigny T, Larchevëque M, Normant H. 1,4 - dialdehyde monoacetals: A new synthesis of dihydrotagetone. Tetrahedron Lett 1976; 17(17): 1379-80.
[http://dx.doi.org/10.1016/S0040-4039(00)78070-1]
[10]
Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. (2nd ed.). New York: John Wiley & Sons Inc. 1996; pp. 317-25.
[11]
Anjaria JV. New crops for food and industry. In: Wickens GE, Haq N, Day P, Eds. Herbal Drugs: Potential for industry and cash. London: Chapman and Hall 1989; pp. 84-92.
[12]
Garg SN, Mehta VK. Acyclic monoterpenes from the essential oil of Tagetes minuta flowers. Phytochemistry 1998; 48(2): 395-6.
[http://dx.doi.org/10.1016/S0031-9422(97)01125-4] [PMID: 9747537]
[13]
Prabuseenivasan S, Jayakumar M, Ignacimuthu S. In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med 2006; 6(1): 39.
[http://dx.doi.org/10.1186/1472-6882-6-39] [PMID: 17134518]
[14]
Komiya M, Takeuchi T, Harada E. Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Behav Brain Res 2006; 172(2): 240-9.
[http://dx.doi.org/10.1016/j.bbr.2006.05.006] [PMID: 16780969]
[15]
Lehrner J, Marwinski G, Lehr S, et al. Ambient odors of orange and lavender reduce anxiety and improve mood in a dental office. Physiol Behav 2005; 86(1-2): 92-5.
[http://dx.doi.org/10.1016/j.physbeh.2005.06.031] [PMID: 16095639]
[16]
Kuriyama H, Watanabe S, Nakaya T, et al. Immunological and psychological benefits of aromatherapy massage. Evid Based Complement Alternat Med 2005; 2(2): 179-84.
[http://dx.doi.org/10.1093/ecam/neh087] [PMID: 15937558]
[17]
Franzios G, Mirotsou M, Hatziapostolou E, Kral J, Scouras ZG, Mavragani-Tsipidou P. Insecticidal and genotoxic activities of mint essential oils. J Agric Food Chem 1997; 45(7): 2690-4.
[http://dx.doi.org/10.1021/jf960685f]
[18]
Farley DR, Howland V. The natural variation of the pulegone content in various oils of peppermint. J Sci Food Agric 1980; 31(11): 1143-51.
[http://dx.doi.org/10.1002/jsfa.2740311104]
[19]
Weglarz Z, Zalecki R. Investigations of dependence of the crop season of peppermint (Mentha piperita L.) herb upon the crop itself and the quality of the raw material. Herba Pol 1985; 31: 175-80.
[20]
Murray MJ, Marble P, Lincoln D, Hefendehl FW. Peppermint oil quality differences and the reason for them. In: Lawrence BM, Mookherjee BD, Willis BJ, Eds. Flavor and Fragrances: A World Perspective. The Netherlands: Elsevier Press Amsterdam 1988; pp. 189-210.
[21]
Voirin B, Brun N, Bayet C. Effects of daylength on the monoterpene composition of leaves of Mentha piperita. Phytochemistry 1990; 29(3): 749-55.
[http://dx.doi.org/10.1016/0031-9422(90)80012-6]
[22]
Marotti M, Piccaglia R, Giovanelli E, Deans SG, Eaglesham E. Effects of planting time and mineral fertilization on peppermint (Mentha piperita l.) essential oil composition and its biological activity. Flavour Fragrance J 1994; 9(3): 125-9.
[http://dx.doi.org/10.1002/ffj.2730090307]
[23]
Kumar S, Bahl JR, Bansal RP, Kukreja AK, Garg SN, Naqvi AA. Profits of Indian menthol mint Mentha arvensis cultivars at different stages of crop growth in northern plains. J Med Arom Plant Sci 2000; 22: 774-86.
[24]
Misra A, Srivastava NK. Influence of water stress on Japanese mint. J Herbs Spices Med Plants 2000; 7(1): 51-8.
[http://dx.doi.org/10.1300/J044v07n01_07]
[25]
Dolzhenko Y, Bertea CM, Occhipinti A, Bossi S, Maffei ME. UV-B modulates the interplay between terpenoids and flavonoids in peppermint (Mentha piperita L.). J Photochem Photobiol B 2010; 100(2): 67-75.
[http://dx.doi.org/10.1016/j.jphotobiol.2010.05.003] [PMID: 20627615]
[26]
Guenther E. The Essential Oils. New York: D Van Nostrand Company Inc. 1949.
[27]
Smith DM, Levi L. Essential oils, treatment of compositional data for the characterization of essential oils. Determination of geographical origins of peppermint oils by gas chromatographic analysis. J Agric Food Chem 1961; 9(3): 230-44.
[http://dx.doi.org/10.1021/jf60115a017]
[28]
Smith DM, Skakum W, Levi L. Determination of botanical and geographical origin of spearmint oils by gas chromatographic and ultraviolet analysis. J Agric Food Chem 1963; 11(3): 268-76.
[http://dx.doi.org/10.1021/jf60127a010]
[29]
Von Hefendehl FW, Ziegler E. Analysis of peppermint oil. Deut Lebens-Ritnds 1975; 8: 287-90.
[30]
Grundschober F. Literature review of pulegone. PerfumFlavorist 1979; 4: 15-7.
[31]
Virmani OP, Datta SC. Oil of spearmint Perfume. Ess Oil Rec 1968; 59: 351-62.
[32]
Turner GW, Croteau R. Organization of monoterpene biosynthesis in Mentha. Immunocytochemical localizations of geranyl diphosphate synthase, limonene-6-hydroxylase, isopiperitenol dehydrogenase, and pulegone reductase. Plant Physiol 2004; 136(4): 4215-27.
[http://dx.doi.org/10.1104/pp.104.050229] [PMID: 15542490]
[33]
Kaiser R, Lamparsky D, Schudel P. Analysis of Buchu leaf oil. J Agric Food Chem 1975; 23(5): 943-50.
[http://dx.doi.org/10.1021/jf60201a021]
[34]
Thomassen D, Slattery JT, Nelson SD. Contribution of menthofuran to the hepatotoxicity of pulegone: Assessment based on matched area under the curve and on matched time course. J Pharmacol Exp Ther 1988; 244(3): 825-9.
[PMID: 3252034]
[35]
Da Rocha MS, Dodmane PR, Arnold LL, et al. Mode of action of pulegone on the urinary bladder of F344 rats. Toxicol Sci 2012; 128(1): 1-8.
[http://dx.doi.org/10.1093/toxsci/kfs135] [PMID: 22499580]
[36]
O’Neil MJ. An Encyclopedia of Chemicals, Drugs, and Biologicals. (15th ed.), Whitehouse, NJ: Merck Sharp & Dohme Corp.: RSC Publishing 2013.
[37]
Sigma Aldrich A. (R)-(+)-Pulegone, MSDS analytical standard. 2009. Available from: http://www.sigmaaldrich.com/catalog/product/aldrich/w296309?lang=en&region=US [Accessed on: 19 June, 2020].
[38]
Oppenauer RV. A method for the dehydrogenation of secondary alcohols to ketones. I. For the production of sterol ketones and sex hormones. Recl Trav Chim Pays Bas 1937; 56(2): 137-44.
[http://dx.doi.org/10.1002/recl.19370560206]
[39]
Corey EJ, Ensley HE, Suggs JW. Convenient synthesis of (S)-(-)-pulegone from (-)-citronellol. J Org Chem 1976; 41(2): 380-1.
[http://dx.doi.org/10.1021/jo00864a047]
[40]
Tamiya J, Sorensen EJ. A spontaneous bicyclization facilitates a synthesis of (−)-hispidospermidin. Tetrahedron 2003; 59(35): 6921-32.
[http://dx.doi.org/10.1016/S0040-4020(03)00936-0]
[41]
Eliel EL, Lynch JE. Asymmetric synthesis of ()-(+)-ethylmethyl--propylcarbinol in high enantiomeric purity. A 1,3-oxathiane derived from (+)-pulegone as chiral adjuvant. Tetrahedron Lett 1981; 22(30): 2855-8.
[http://dx.doi.org/10.1016/S0040-4039(01)81768-8]
[42]
Tu YQ, Moore CJ, Kitching W. From (R)-(+)-pulegone to (2S,4R,6R,8S)-2,4,8-trimethyl-1,7-dioxaspiro[5.5]undecane - A unique spiroacetal from the insect Kingdom. Tetrahedron Asymmetry 1995; 6(2): 397-400.
[http://dx.doi.org/10.1016/0957-4166(95)00023-I]
[43]
Cossy J, Bouzbouz S, Hakiki A. Michael radical additions two short efficient syntheses of (+)-conocephalenol from (R)-pulegone. Tetrahedron 1999; 55(37): 11289-94.
[http://dx.doi.org/10.1016/S0040-4020(99)00636-5]
[44]
Davies SG, Bhalay G. A formal synthesis of (−)-pumiliotoxin C. Tetrahedron Asymmetry 1996; 7(6): 1595-6.
[http://dx.doi.org/10.1016/0957-4166(96)00190-5]
[45]
Watanabe S. Circular Dichroism Studies of Ring-conf ormational and rotational equilibria in 2-Isopropenylcyclohexanones. Bull Chem Soc Jpn 1973; 46(5): 1546-9.
[http://dx.doi.org/10.1246/bcsj.46.1546]
[46]
Alexander CW, Jackson WR. Addition reactions of conjugated double bonds. Part IV. The stereochemistry of cyanide ion addition to some αβ-unsaturated ketones and their π-allylpalladium derivatives. J Chem Soc, Perkin Trans 2 1972; 11(11): 1601-4.
[http://dx.doi.org/10.1039/P29720001601]
[47]
Szente L, Szejtli J, Chau LT. Effect of cyclodextrin complexation on the reduction of menthone and isomenthone. J Inclusion Phenomena 1987; 5(4): 439-42.
[http://dx.doi.org/10.1007/BF00664100]
[48]
Dhingra A, Chopra B, Bhardwaj S, Dhar KL. Synthesis and Characterization of novel Pulegone derivatives as substitutes of 4-(1,1 dimethylethyl) cyclohexan-1-ol acetate. J Pharm Res 2011; 4(1): 19-21.
[49]
Calas M, Calas B, Giral L. Bull Soc Chim Fr 1973; 2: 2079.
[50]
Ravichandran R, Divakar S. β-Cyclodextrin and its derivatives directed axial attack of hydride ion in the reduction of (R)-(+)-pulegone and (2S,5R)-(−)- menthone. J Mol Catal Chem 1996; 109(3): 201-8.
[http://dx.doi.org/10.1016/1381-1169(96)00034-9]
[51]
Soucy C, Lacoste JÉ, Breau L. Synthesis of 2-isoxazolines from olefins derived from norephedrine and pulegone. Tetrahedron Lett 1998; 39(50): 9117-20.
[http://dx.doi.org/10.1016/S0040-4039(98)02060-7]
[52]
Ravi P, Ravichandran R, Divakar S. Stereoselective hydrogenation of (R)-(+)-pulegone and (2 S, 5 R)-(−)-menthone in presence of β-cyclodextrin and its derivatives. J Mol Catal Chem 1999; 148(1-2): 145-55.
[http://dx.doi.org/10.1016/S1381-1169(99)00036-9]
[53]
Norin T, Theander O, Lindberg B, McKay J, Theander O, Flood H. The absolute configuration of the thujane group. Acta Chem Scand 1962; 16: 640-8.
[http://dx.doi.org/10.3891/acta.chem.scand.16-0640]
[54]
Ho TL. Enantioselective synthesis: Natural products synthesis from chiral terpenes. New York: Wiley 1992.
[55]
Srikrishna A, Gharpure SJ, Praveen KP. A simple, enantiospecific approach to both enantiomers of 1α,25-dihydroxyvitamin D3 A-ring precursors from R-carvone. Tetrahedron Lett 2000; 41(17): 3177-80.
[http://dx.doi.org/10.1016/S0040-4039(00)00325-7]
[56]
Meulemans TM, Stork GA, Macaev FZ, Jansen BJM, de Groot A. Total synthesis of dihydroclerodin from ( R )-(−)-carvone. J Org Chem 1999; 64(25): 9178-88.
[http://dx.doi.org/10.1021/jo991151r]
[57]
Silvestri MG. Facile synthesis of (+)-(R)-4-methyl-2-cyclohexen-1-one. J Org Chem 1983; 48(14): 2419-20.
[http://dx.doi.org/10.1021/jo00162a025]
[58]
Lee HW, Ji SK, Lee C, Lee JH. 5-step synthesis of (R)-(+)-4-methyl-2-cyclohexenone starting from (+)-pulegone. J Org Chem 1996; 61: 2542.
[http://dx.doi.org/10.1021/jo9517656]
[59]
Hua DH, Venkataraman S. Synthesis of optically pure 4-methyl-2-cyclohexenone A use chiral building block. J Org Chem 1988; 53(5): 1095-7.
[http://dx.doi.org/10.1021/jo00240a033]
[60]
Oppolzer W, Petrzilka M. (R)-(+)-5-methyl-2-cyclohexenone from (+)-pulegone. Helv Chim Acta 1978; 61: 2755.
[http://dx.doi.org/10.1002/hlca.19780610802]
[61]
Stanfill SB, Calafat AM, Brown CR, et al. Concentrations of nine alkenylbenzenes, coumarin, piperonal and pulegone in Indian bidi cigarette tobacco. Food Chem Toxicol 2003; 41(2): 303-17.
[http://dx.doi.org/10.1016/S0278-6915(02)00230-2] [PMID: 12480305]
[62]
Hall RL, Oser BL. Recent progress in the consideration of flavoring ingredients under the food additives amendment III GRAS substances. Food Technol 1965; 19: 253-71.
[63]
Tyler VE. The Honest Herbal. Binghamton, New York: Pharmaceutical Products Press 1993; pp. 243-4.
[64]
a) Carson R, Patel K, Pillai S, Granger SP. Cosmetic skin care compositions containing pulegone. U.S. Patent 6,391,324, 2002.;
b) Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J Pharm Pharmacol 2015; 67(4): 473-85.
[http://dx.doi.org/10.1111/jphp.12334] [PMID: 25557808]
[65]
Hoppe HA. Drogenkunde. 8th Ed. Berlin: Walter de Gruyter 1975; 1: pp. 764.
[66]
List PH, Horhammer L. Hager’s Handbook of Pharmaceutical Practice. (4th ed.), Berlin: Springer-Verlag 1976.
[67]
Foster S, Duke J. A field guide to medicinal plants. Boston, MA: Houghton Mifflin Co. 1990; p. 190.
[68]
Skenderi G. Herbal Vade Mecum. Rutherford, NJ:, Ed, Herbacy Press 2003; p. 287.
[69]
Karousou R, Balta M, Hanlidou E, Kokkini S. “Mints”, smells and traditional uses in Thessaloniki (Greece) and other Mediterranean countries. J Ethnopharmacol 2007; 109(2): 248-57.
[http://dx.doi.org/10.1016/j.jep.2006.07.022] [PMID: 16962274]
[70]
McClanahan RH, Thomassen D, Slattery JT, Nelson SD. Metabolic activation of (R)-(+)-pulegone to a reactive enonal that covalently binds to mouse liver proteins. Chem Res Toxicol 1989; 2(5): 349-55.
[http://dx.doi.org/10.1021/tx00011a013] [PMID: 2519826]
[71]
Madyastha KM, Raj CP. Biotransformations of R-(+)-pulegone and menthofuran invitro: Chemical basis for toxicity. Biochem Biophys Res Commun 1990; 173(3): 1086-92.
[http://dx.doi.org/10.1016/S0006-291X(05)80897-6] [PMID: 2268314]
[72]
Khojasteh-Bakht SC, Chen W, Koenigs LL, Peter RM, Nelson SD. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: Evidence for formation of a furan epoxide. Drug Metab Dispos 1999; 27(5): 574-80.
[PMID: 10220485]
[73]
Gordon WP, Huitric AC, Seth CL, McClanahan RH, Nelson SD. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 1987; 15(5): 589-94.
[PMID: 2891472]
[74]
Daferera DJ, Ziogas BN, Polissiou MG. The effectiveness of plant essential oils on the growth of Botrytis cinerea, Fusarium sp. and Clavibacter michiganensis subsp. michiganensis. Crop Prot 2003; 22(1): 39-44.
[http://dx.doi.org/10.1016/S0261-2194(02)00095-9]
[75]
Economou KD, Oreopoulou V, Thomopoulos CD. Antioxidant activity of some plant extracts of the family labiatae. J Am Oil Chem Soc 1991; 68(2): 109-13.
[http://dx.doi.org/10.1007/BF02662329]
[76]
Kaur C, Kapoor HC. Anti-oxidant activity and total phenolic content of some Asian vegetables. Int J Food Sci Technol 2002; 37(2): 153-61.
[http://dx.doi.org/10.1046/j.1365-2621.2002.00552.x]
[77]
Gulluce M, Sahin F, Sokmen M, et al. Antimicrobial and antioxidant properties of the essential oils and methanol extract from Mentha longifolia L. ssp. longifolia. Food Chem 2007; 103(4): 1449-56.
[http://dx.doi.org/10.1016/j.foodchem.2006.10.061]
[78]
Gata-Gonçalves L, Nogueira JMF, Matos O, Bruno de Sousa R. Photoactive extracts from Thevetia peruviana with antifungal properties against Cladosporium cucumerinum. J Photochem Photobiol B 2003; 70(1): 51-4.
[http://dx.doi.org/10.1016/S1011-1344(03)00024-1] [PMID: 12745247]
[79]
Kurucheve V, Echilan JG, Jayaraj J. Screening of higher plants for the fungitoxicity against R. solani in vitro. Indian Phytopathol 1997; 50(2): 235-41.
[80]
Saxena VK, Jain SK. Thevetiaperuvianakernel oil: A potential bactericidal agent. Fitoterapia 1990; 61(4): 348-9.
[81]
Obasi NB, Igboechi AC. Seed-oil distillates of Thevetiaperuviana (SYN. T. neriifolia): Analysis and antibacterial activity. Open Vet J 2011; 1(1): 28-31.
[82]
Fournet A, Rojas de Arias A, Charles B, Bruneton J. Chemical constituents of essential oils of Muña, Bolivian plants traditionally used as pesticides, and their insecticidal properties against Chagas’ disease vectors. J Ethnopharmacol 1996; 52(3): 145-9.
[http://dx.doi.org/10.1016/0378-8741(96)01406-7] [PMID: 8771455]
[83]
Ciganda C, Laborde A. Herbal infusions used for induced abortion. J Toxicol Clin Toxicol 2003; 41(3): 235-9.
[http://dx.doi.org/10.1081/CLT-120021104] [PMID: 12807304]
[84]
Conway GA, Slocumb JC. Plants used as abortifacients and emmenagogues by Spanish New Mexicans. J Ethnopharmacol 1979; 1(3): 241-61.
[http://dx.doi.org/10.1016/S0378-8741(79)80014-8] [PMID: 232204]
[85]
Anderson IB, Mullen WH, Meeker JE, et al. Pennyroyal toxicity: Measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996; 124(8): 726-34.
[http://dx.doi.org/10.7326/0003-4819-124-8-199604150-00004] [PMID: 8633832]
[86]
Black DR. Pregnancy unaffected by pennyroyal usage. J Am Osteopath Assoc 1985; 85(5): 282.
[PMID: 4044323]
[87]
Bakerink JA, Gospe SM Jr, Dimand RJ, Eldridge MW. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996; 98(5): 944-7.
[http://dx.doi.org/10.1542/peds.98.5.944] [PMID: 8909490]
[88]
Sullivan JB Jr, Rumack BH, Thomas H Jr, Peterson RG, Bryson P. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979; 242(26): 2873-4.
[http://dx.doi.org/10.1001/jama.1979.03300260043027] [PMID: 513258]
[89]
Thorup I, Würtzen G, Carstensen J, Olsen P. Short term toxicity study in rats dosed with pulegone and menthol. Toxicol Lett 1983; 19(3): 207-10.
[http://dx.doi.org/10.1016/0378-4274(83)90120-0] [PMID: 6658833]
[90]
Olsen P, Thorup I. Neurotoxicity in rat doses with peppermint oil and pulegone. Arch Toxicol 1984; 7: 408-9.
[91]
European Medical Agency. Specialized Information Services: Public statement on the use of herbal medicinal productscontaining pulegone and menthofuran. Available from: www.ema.europa.eu/en/documents/scientific-guideline/public-statement-use-herbal-medicinal-products-containing-pulegone-menthofuran-revision-1_en.pdf (Accessed on: August 1, 2021).

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy