P-Menthane-2,9-diol

Eucalyptus citriodora Hook f (Lemon gum) The oil of the fresh leaves of E. citriodora (2.2-8.3%), a tree introduced into Kenya from Australia (68), has been well researched in Kenya. Results indicate that there are two chemical varieties that were introduced. The chief essential oil constituents of one variety are citronellal (65-88%), citronellol (2-25%) and isopulegol (2-19%). In constrast, the second variety has as its major essential oil consitutents citronellol (32-52%), citronellal (38-59%) and 1,8-cineole (2-19%) (68,69). The essential oil is regarded as a perfumery oil. This plant is the second most commercially important Eucalyptus species in the essential oil trade and is only second to E. smithii Baker (69). The aromatic oil is used in soaps, creams and lotions due to its desirable odor properties, and as with many other essential oils is also used extensively in many technical preparations to mask other industrial malodors. A highly active mosquito repellent compound, p-menthane 3,8-diol has been isolated from the waste water of distillation of E. citriodora. There are now many commercial mosquito repellents based on this waste water (70-73). 

Vanek T, Novotny M, Podlipna R, Saman D, Valterova 1 (2003) Biotransformation of Citronellal by Solanum aviculare Suspension Cultures Preparation of p-Menthane-3,8-diols and Determination of their Absolute Configurations. J Nat Prod 66 1239... 

Based on the aforementioned results, it is obvious that (+)-3p-hydroxy-l,8-cineole (123b) is formed mainly in the biotransformation of 1,8-cineole (122), (+)-3a-hydroxy-l,8-cineole (123b), and (+)-3-oxo-l,8-cineole (126a) by S. ikutamanensis Ya 2 1. The production of (+)-3p hydroxy-l,8-cineole (123b) is interesting, because it is a precursor of mosquito repellent, p-menthane-3,8-diol (142aa ) (Noma and Nishimura, 1981) (Figure 19.136). 

Citronellal (135) can also be converted to the cis- and /ra s-p-menthane-3,8-diols [92471-23-3] (209) and [91739-72-9] (210), respectively, by reaction with dilute acids as shown in Fig. 8.47 [284, 285]. The glycol mixture can be readily purified by distillation and the two isomers easily separated. The glycols are useful as coolants and as insect repellents, as is citronellal itself, and are especially effective against mosquitos (286). Derivatives of the glycols have been prepared and are useful as insecticides and plant growth regulators (287). 

Figure 4.7 (See color insert.) Pharmacophore of p-menthane-3,8-diol (PMD) analogs, (a) Mapping of the pharmacophore on the PMD analogs with better repellent activity, (b) Mapping of the pharmacophore on the PMD analogs with poor repellent activity.

D. Strickman, PMD (p-Menthane-3,8-Diol) and Quwenling In Insect Repellents Principles, Methods, and Uses, Debboun, M. Frances, S. P Strickman, D., Eds. CRC Press Boca Raton, FL, 2007, pp. 347-351. 

Several other commercially available natural insect repellents also use monoterpenoids from oils of cinnamon, lemongrass, rosemary, and lemon eucalyptus. Other specific monoterpenoids used as active ingredients in repellents are phenylethyl propionate (from peanuts) and p-menthane-3,8-diol (from lemon eucalyptus) (Figure 5.1). 

EPA. p-Menthane-3,8-diol (011550) Biopesticide registration eligibility document, http //www.epa. gov/oppbppdl/biopesticides/ingredients/tech docs/tech 011550.htm, Washington, DC, 1998. 

This plant occupies an interesting position among botanical repellents. Although the essential oil from this plant does not demonstrate substantial repellent activity, the by-product of the hydrodistillation process has been shown to be a very effective repellent. The active component is p-menthane-3,8-diol (PMD) and was first identified in China through a screening process of plants to identify potential repellent properties in the 1960s and is known as quwenling. 

The biopesticide, IR3535 (3-(A-butyl-Af-acetyl)-aminopiopionic acid ethyl ester) has been in use for the longest of the three having been introduced in Europe in 1979 and the United States in 1999. No case studies could be identified concerning reported toxicity, although it is difficult to gauge the extent to which it has been formulated into various products. Eurther, very little in terms of kinetics and toxicity profile is available in the literature. A similar lack of data applies to p-menthane-3,8-diol. 

The use of topical repellents applied to exposed skin is the most important personal intervention against vectors of diseases, and numerous studies have been undertaken to enumerate the protection against biting vectors, especially mosquitoes. The use of repellent active ingredients such as A,A-diethyl-3-methylbenzamide (deet), 2-(2-hydroxyethyl)-l-piperidinecarboxylic acid 1-methylpropyl ester (icaridin, picaridin), lemon eucalyptus oil (p-menthane-3,8-diol) and ethyl butylacetylaminopropionate (IR3535), as well as several infrequently used synthetic and naturally derived active ingredients are discussed in detail in Chapter 19. 

Aedes aegypti Sindbis (Flavivirus) Oil of lemon eucalyptus (30%, 65% of p-menthane-3,8-diol) No difference... 

Figure 4.8 Polarity directions and molecular electrostatic potential (MEP) at 20 kcal/mol of p-menthane-3, 8-diol analogs.

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