Botanicals from the Piperaceae and Meliaceae of the American

Chapter 5

Botanicals from the Piperaceae and Meliaceae of the American Neotropics: Phytochemistry 1

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Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on October 23, 2014 | http://pubs.acs.org Publication Date: March 19, 1997 | doi: 10.1021/bk-1997-0658.ch005

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S. MacKinnon , D. Chauret , M. Wang , R. Mata , R. Pereda-Miranda , A. Jiminez , C. B. Bernard , H. G. Krishnamurty , L. J. Poveda , P. E. Sanchez-Vindas , J. T. Arnason , and T. Durst 1

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Ottawa Carleton Institutes of Chemistry and Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada Departamento de Farmacia, Facultad de Quimica, Universidad Nacional Autonoma de México, Coyoacan 041510, Mexico Department of Chemistry, University of Delhi, Delhi 110007, India Universidad Nacional, Heredia, apdo 86-3000, Costa Rica

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Phytochemicals with insecticidal properties have been isolated and studied from the neotropical Piperaceae, Meliaceae and related families. Investigation of 16 neotropical Piper spp. led to the isolation of active amides, lignans and prenylated benzoic acid derivatives. Recent investigations with the Meliaceae and related families have led to isolation of humilinolidesfromSwietenia, of C-D spiro-triterpenoids, a new of terpenoidsfromRuptiliocarpon and new steroids and limonoidsfromTrichilia.

A recent survey (1) indicates that natural products continue to be an important source of new agrochemicals. While there are many families of plants of interest (2) for the development of botanical insecticides, including the Annonaceae, Araceae, Asteraceae, Guttiferae, Meliaceae and Piperaceae, we have concentrated on the latter two families as bioactive taxa which may provide useful materials with low mammalian toxicity. Insecticidal compounds from the Piperaceae The Piperaceae (Pepper family) have long been used in traditional agriculture as insecticides and are good candidates for safe botanicals because of their widespread use as spices and medicinal plants as remedies for stomach, tooth and other ailments (3). The active compounds include acutely acting amides and slower acting, growth reducing lignans which may also act as insecticide synergists. Well studied botanicalsfromthis family include extracts of Guinea pepper, Piper guineensefromAfrica, as well as black pepper, P. nigrum and a medicinally used wild pepper, P. retrqfractumfromAsia. P. guineensefruitscontain pipeline, trichostachine and N-isobutyl-trans-2-4 eicosadienamide as active agents (4). P. retrqfractum fruits produce pipeline (Figure 1), pipernonaline, piperoctadecalidine and pipereicosalidine and a variey of other amides (5). Synergism between co-occurring pipericide and other insecticidal amides of black pepper has been well established by Miyakado et α/. (6) 5

Corresponding author © 1997 American Chemical Society

In Phytochemicals for Pest Control; Hedin, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.


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PHYTOCHEMICALS FOR PEST CONTROL

Less work has been done on new world Piper spp. with respect to their insecticidal activity. We recently completed a survey (7) of 16 neotropical Piper spp. for insecticidal activity and identified P. tuberculatum as the most active insecticidal extract in trials with European corn borer (ECB), Ostrinia rmbilalis and mosquito larvae, Aedes atropalpus. Bioassay guided isolation led to the identification of dihydrolonguininine as the active principle (Figure 1). A second species, P. aduncum was found to have an active fraction containing large amounts of the phenylpropanoid dillapiol (Figure 1) which we had identified previously as a potent polysubstrate monooxygenase inhibitor. Similar compounds have been isolated by NairfromJamaican Piper spp. (14). Subsequent study (8) of the active fraction ofP. decurrens led to the identification of several co-CKairring lignans including conocarpon, decurrenal and eupomatenoid-5 and-6 (Figure 2). P. guanacastense has recently afforded us several larvicidal prenylated benzoic acid derivatives. Methyl 3 -(3 -methyl-2-butenyl)-4hydroxy benzoate (Figure 1) was isolated as the major principle which had noteworthy insecticidal activity to mosquito larvae. While these are not unique in the family (13), they are not common and have been shown to possess insecticidal activity now for thefirsttime. Tropical Meliaceae Similarly, the Asian Meliaceae (Mahogany family) are noted for the production of useful antifeedant and growth reducing substances. These include the limonoids which have been commercialized: azadirachtin in the US and toosendaninfromMelia azedarach in China (17) . Aglaia odorata extractsfromThailand and ndghboring SE. Asian countries are also promising and contain an active benzofuran, rocaglamide, that is as active as azadirachtin (18) . However, as yet no commercial Tropical American product has been developed, although considerable phytochemical work has been done on neotropical species. Our examination of over 50 extracts of 35 species of neotropical Meliaceae was undertaken to identify a variety of promising extracts against the Lepidopteran pests, ECB and Peridroma soucia (9). The most active extract to ECB was Ruptiliocarpon caracolito, which was originally thought to be a member of the Meliaceae based on wood anatomy and other characteristics, but has recently been identified as the only American species of the Lepidobotryceae. The insecticidalfractionof this species has now yielded over a dozen distinct C-D spiro-triterpenoids some of which are illustrated in Figure 3. These represent an entirely novel biosynthetic class of terpenoid, possibly produced via a C-13, C-18 epoxyfriedelin derivative (10). The more highly oxygenated compounds of this family, especially spirocaracolitones Ε and F are very active against corn borer but supply of this rainforest endemic of the Osa peninsula of Costa Rica may limit any potential application. Their antifungal activity was modest as was their activity against malaria parasites (11). Other active extracts included preparations of the genera Cedrela, Trichilia and Swietenia. The main active ingredient in the insecticidalfractionof wood of C. odorata was found to be the the limonoid gedunin, which has moderate to good growth reducing activity to ECB and can be sourced in quantitiesfromwood rather than scarce seed. An extraction method based on the use of toluene as the extraction solvent has been developed which gives rapid access to large amounts of gedunin. Sawdust obtained from some Central American sources yield up to 0.5% gedunin. In order to study the structural features of gedunin that were essential for activity, MacKinnon (11) synthesized and tested a series of derivatives for testing at 50 ppm in borer diets. Of these, the 1,2 epoxy-derivative and the 23 acetyl derivative were more active than gedunin (Figure 4). The 1,2 dihydro-3 β-gedunol was inactive while the 1,2 dihydro-, hexahydro-, 21-acetyl- and 7-deactyl- gedunin derivatives In Phytochemicals for Pest Control; Hedin, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.

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Botanicals from the American Neotropics

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CO' O Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on October 23, 2014 | http://pubs.acs.org Publication Date: March 19, 1997 | doi: 10.1021/bk-1997-0658.ch005

pipenne C0 Me 2

dihydropiperlonguminine

methyl 3-(3-methyl-2-butenyl)4-hydroxybenzoate

Figure 1. Compounds isolatedfromactive neotropical Piper spp.

OMe

conocarpan

eupomatenoid-5

decurrenal

eupomatenoid-6

Figure 2. Neolignans form Piper decurrens




1, spirocaracolitone A

2, spirocaracolitone B: R = R = R = Ac 3, spirocaracolitone C: Κ = H; R = Ac; R = COPh 4, spirocaracolitone D: R^ Ac; R = H; R = COPh 1

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5, spirocaracolitone E: R = COC(CH )=CHCH 6, spirocaracolitone F: R = COPh 3

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Figure 3 Spiro-caracolitonesfromRuptiliocarpon caraclito



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Botaniccds front the American Neotropics

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23-acetylgedunin

Figure 4. Gedunin derivative with greater activity than gedunin.

were less active than gedunin. Gedunin also has a potent antimalarial activity, and these derivatives are being studied in trials with the chloroquine resistant forms of Plasmodium falciparum in collabooration with Pezzuto and AngerhofFer at the University of Chicago. Further study of seven speciesfromthe genus Trichilia identified Τ glabra and Τ hirta extracts as potent growth reducers for Lepidoptera (16). Two new steroidal compounds,3-hydroxypregnane-2,16-dione and 2-hydroxyandrosta-1,4-diene-3, 16-dione (12) were identifiedfromthe insecticidalfractionsobtained from T. hirta (Figure 5). Trichilia martiana fruits yielded two limonoids, methyl angolensate and a new limonoid as well as 2(Z,Z)-8,11-heptadecadienylfuran (Figure 6). These compounds are currently undergoing evaluation for their bioactivity. Study of Swietenia humilis by Mata's group at the Universidad Nacional Autonoma de Mexico (15) yielded several humilinolides. In evaluations with ECB, some of these compounds (Figure 7) were comparable to toosendanin in insecticidal activity. Extraction of C. sahadorensis bark by Mata's group has recently yielded the growth reducing limonoid, cedrelanolide (Figure 8), which is less active than the humilinolides, but could be produced in larger quantities from sawmill waste. Conclusion: Whh over 60 species of Trichilia in the Americas and over 100 Piper spp. in Costa Rica alone (19), the opportunities for developing useful natural products from the Meliaceae and Piperaceae are promising, since relatively few of the species have been examined phytochemically. While the activity of the pure compounds has been or is being reported in separate research contributions in the companion paper by Assabgui et al, we evaluated the possibility of using standardized insecticidal extracts derivedfromthese materials as practical insecticides.



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3-hydroxypregnane-2,16-dione

2-hydroxyandrosta-l ,4-diene-3,16-dione

Figure 5. New compoundsfromTrichilia hirta wood.

Methyl angolensate

novel limonoid

2-(Z,Z)-8,l 1-heptadecadienylfuran

Figure 6. PhytochemicalsfromTrichilia martiana fruits.



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OCOCH(Me)2

humilinolide A: R = OH humilinolide B: R * OAc

OR,

humilinolide C: R » H; R ι » COC(Me)=CHMe; R 2 » Ac humilinolide D: R - OAc; R 1 » Ac; R2 = H

Figure 7Limonoids isolatedfromSwietenia humilis.

Cedrelanollde

Figure 8. A new rearranged limonoidfromCedrela sahadorensis In Phytochemicals for Pest Control; Hedin, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.


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Acknowledgement: This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), and Forestry Canada (Natural Product Network). R. Pereda-Miranda was recipient of a foreign resesearcher award from NSERC Literature cited:


1. Pillmoor, J.B., Wright, K. and Terry, A.S. Pestic. Sci. 1993, 39, 131-140.

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2. Isman, M.B. Rev. Pestic. Toxicol. 1995, 3, 1-20. 3. Shultes R.E. and Rauffauf, R., 1990, "The Healing Forest", Dioscorides Press, Oregon. 4. Addae-Mensah, I., Tort, F.G., Oppong, I., Baxter, I. and Sanders, J. Phytochem. 1977, 16, 483-485. 5. Ahu J.W. Ahu, M.J., Zee, O.P., Kim., E.J., Lee, H.J. and Kubo, I. Phytochem. 1992 31 3609-3619. 6. Miyakado, M., Nakayama, I. Yoshioda, H. Agr. Biol. Chem. 1983,44, 1701-1703. 7. Bernard, C.B., Krishnamurty, H.G., Chauret, D., Sanchez, P.E., San Roman, L., Poveda, L.J. and Hasbun, C. J. Chem. Ecol. 1995, 21, 801-814. 8. Chauret,D. Bernard, C.B., Arnason, J.T., Durst,T., Krishnamurty, H.G. Sanchez Vindas, P., Moreno, N., San Roman, L. And Poveda, L. J. Nat. Prod. 1996, 59, 152-155 9. Arnason, J.T., MacKinnon, S., Durst, T., Philogene, B.J.R., Hasbun, C., Sanchez- Vindez, P.E., San Roman, L., Poveda,L.J., Isman, M.B. Recent Advances in Phytochem. 1992, 28, 107-131. 10 MacKinnon, S., Durst, T., Arnason, J.T., Bensimon, C., Sanchez- Vindez, P.E., San Roman, L., Poveda, L.J. and Hasbun, C. Tetrahedron 1994, 35, 1385-1388. S. MacKinnon, 1995. Bioactive triterpenoids of the Rutales. Ph D. Thesis, University of Ottawa.

12. D. Chauret et al unpublished. 13. Orjala, J., Erdelmeier, C.A.J., Wright, A.D., Rali, T. and Sticher O. Phytochem 1993, 34, 813-818. 14. Nair, M.G., Burke,B . A .J. Agric. Food Chem. 1990, 38, 1093-1096. 15. Segura-Correa, R., Mata, R., Anaya Α., Hernandez, B., Villena, R., Soriano-Garcia, R. and Bye, R. and Linares E., J. Nat Prod. 1993, 56, 1567-1575.


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16. Xie, Y.S., Gunning, P., MacKinnon, S., Isman, M.B., Arnason, J.T., Towers, G.H.N., Sanchez, P.E. and Hasbun, C. Biochem. Syst. and Ecol., 1994, 22, 129-136. 17. Chiu, S.F., pp 642-646 in "The Neem Tree", H. Schmuterer ed. 1995. VCH, New York.


18. Janprasert, J., Satasook, P. Sukumalanand, P., Champagne, D.E., Isman, M.B., Wiriyachitra, P. and Towers, G.Η.Ν.Phytochemistry, 1993,32,67-70. 19. Pennington, T., Styles, B., and Taylor, D. Flora neotropica monograph no. 28. N.Y. Botanical garden. 1991.


Botanicals from the Piperaceae and Meliaceae of the American

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