Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Alkamides: a critical reconsideration of a multifunctional class of unsaturated fatty acid amides

  • 1033 Accesses

  • 18 Citations


Alkamides are natural products formed by connecting straight-chain, mostly unsaturated, aliphatic acids with various amines by an amide linkage. More than 300 derivatives are known from eight plant families consisting of various combinations of 200 acids with 23 amines. Apart from a few saturated derivatives alkamides with unsaturated acid parts are grouped into compounds with purely olefinic patterns and those with olefinic and acetylenic linkages. Derived from C18 oleic acid the acid parts are modified either by chain elongations to C28 or by oxidative shortenings to C4 acid residues. Substrate and regiospecific desaturases and acetylenases are responsible for their characteristic patterns of unsaturation. Amine parts are derived from various amino acids by decarboxylation. Beside the widespread isobutylamines alkamides with six- and five-membered ring amines and those with phenylalanine derived amines are characteristic for the Asteraceae and Piperaceae while benzylamines are restricted to the Brassicaceae. Within the Asteraceae 2-methylbutylamine distinguishes the tribe Heliantheae from Anthemideae characterized by ring amines. Alkamides with elongated olefinic acid parts are mainly found in Piperaceae and Brassicaceae while acetylenic acid parts are typical for Asteraceae. A wide variety of biological activities ranges from the characteristic pungent/tingling property and high insecticidal toxicity to significant antifungal, antibacterial, antiprotozoal, molluscicidal, cercaricidal, and acaricidal activity. They also act as plant growth-promoting substances. Position and stereochemistry of the double bonds are essential for the different qualities of the pungent taste. Medically alkamides possess anti-inflammatory and analgesic properties and are responsible for immuno-modulatory and cannabinomimetic effects.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9


  1. 1.

    In addition, a saturated C28 tyramide (f) has been isolated from Zanthoxylum gilletii (Wansi et al. 2009).


  1. Abarbri M, Parrain JL, Duchêne A (1998) A synthetic approach to natural dienamides of insecticidal interest. Synth Commun 28:239–249

  2. Achenbach H, Fietz W, Wörth J, Waibel R, Portecop J (1986) Constituents of tropical medicinal plants, IXX. GC/MS-investigations of the constituents of Piper amalago—30 new amides of the piperine-type. Planta Med 52:12–18

  3. Acree F Jr, Jacobson M, Haller HL (1945) An amide possessing insecticidal properties from the roots of Erigeron affinis DC. J Org Chem 10:236–242

  4. Adesina SK, Reisch J (1988) Arnottianamide and other constituents of Zanthoxylum gillettii root. J Nat Prod 51:601–602

  5. Ahn JW, Ahn MJ, Zee OP, Kim EJ, Lee SG, Kim HJ, Kubo I (1992) Piperidine alkaloids from Piper retrofractum fruits. Phytochemistry 31:3609–3612

  6. Aihara T (1950) On the principles of Xanthoxylum piperitum DC. II. The isolation of sanshoöls and the structure of sanshoöl I. J Pharm Soc Jpn 70:405–409

  7. Ainslie RD, Barchi JJ Jr, Kuniyoshi M, Moore RE, Mynderse JS (1985) Structure of malyngamide C. J Org Chem 50:2859–2862

  8. Althaus JB, Kaiser M, Brun R, Schmidt TJ (2014) Antiprotozoal activity of Achillea ptarmica (Asteraceae) and its main alkamide constituents. Molecules 19:6428–6438

  9. Andrade-Neto M, Mendes PH, Silveira ER (1996) An imidazole alkaloid and other constituents from Pilocarpus trachyllophus. Phytochemistry 42:885–887

  10. Annalakshmi R, Uma R, Subashchandran G, Muneeswaran A (2012) A treasure of medicinal herb—Anacyclus pyrethrum, a review. Indian J Drugs Dis 1:59–67

  11. Ardjomand-Woelkart K, Bauer R (2014) Echinacea: a survey of current literature [Echinacea: Eine Bestandsaufnahme der neueren Literatur]. Z Phytother 35:128–134

  12. Artaria C, Maramaldi G, Bonfigli A, Rigano L, Appendino G (2011) Lifting properties of the alkamide fraction from the fruit husks of Zanthoxylum bungeanum. Int J Cosmet Sci 33:328–333

  13. Asano M, Kanematsu T (1927) Ueber die Bestandteile von Spilanthes acmella L. f. fusca Makino. J Pharm Soc Jpn 544:521–525

  14. Asano M, Kanematsu T (1931) Über Sanshool, einen Bestandteil von Xanthoxylum piperitum D. C. J Pharm Soc Jpn 51:384–390

  15. Asano M, Kanematsu T (1932) Über die Konstitution des Spilanthols, des scharfen Prinzips der Parakresse. Ber Dtsch Chem Ges 65:1602–1604

  16. Aza-González C, Núñez-Palenius HG, Ochoa-Alejo N (2011) Molecular biology of capsaicinoid biosynthesis in chili pepper (Capscicum spp.). Plant Cell Rep 30:695–706

  17. Bader M, Stark TD, Dawid C, Lösch S, Hofmann T (2014) All-trans-configuration in Zanthoxylum alkylamides swaps the tingling with a numbing sensation and diminishes salivation. J Agric Food Chem 62:2479–2488

  18. Bae SS, Ehrmann BM, Ettefagh KA, Cech NB (2010) A validated liquid chromatography-electrospray-ionization-mass spectrometry method for quantification of spilanthol in Spilanthes acmella (L.) Murr. Phytochem Anal 21:438–443

  19. Banerji A, Pal SC (1982) A new alkamide from Piper sylvaticum. Phytochemistry 21:1321–1323

  20. Banerji A, Pal SC (1983) Total synthesis of sylvamide, a Piper alkamide. Phytochemistry 22:1028–1030

  21. Bauer R, Remiger P, Wagner H (1988) Alkamides from the roots of Echinacea purpurea. Phytochemistry 27:2339–2342

  22. Bauer R, Remiger P, Wagner H (1989) Alkamides from the roots of Echinacea angustifolia. Phytochemistry 28:505–508

  23. Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D (2008) Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels. Nat Neurosci 11:772–779

  24. Binns SE, Livesey JF, Arnason JT, Baum BR (2002) Phytochemical variation in Echinacea from roots and flowerheads of wild and cultivated populations. J Agric Food Chem 50:3673–3687

  25. Bohlmann F, Dallwitz E (1974) Notiz über die Biogenese von Polyinamiden. Chem Ber 107:2120–2122

  26. Bohlmann F, Grenz M (1966) Über die Inhaltsstoffe aus Echinacea-Arten. Chem Ber 99:3197–3200

  27. Bohlmann F, Hoffmann H (1983) Further amides from Echinacea purpurea. Phytochemistry 22:1173–1175

  28. Bohlmann F, Zdero C (1967) Über zwei neue Isobutylamide aus Chrysanthemum frutescens L. Chem Ber 100:104–106

  29. Bohlmann F, Zdero C (1970) Die Inhaltsstoffe aus Anthemis fuscata Brot. Chem Ber 103:2856–2859

  30. Bohlmann F, Zdero C (1973) Neue Inhaltsstoffe aus Achillea-Arten. Chem Ber 106:1328–1336

  31. Bohlmann F, Zdero C (1979) Neue C10-Säureamide, Furaneremophilane und andere Inhaltsstoffe aus bolivianischen Senecio-Arten. Phytochemistry 18:125–128

  32. Bohlmann F, Burkhardt T, Zdero C (1973) Naturally occurring acetylenes. Academic Press, London

  33. Bohlmann F, Zdero C, Suwita A (1974) Weitere Amide aus der Tribus Anthemideae. Chem Ber 107:1038–1043

  34. Bohlmann F, Fritz U, Dutta L (1980a) Neue Acetylenverbindungen aus Leucanthemum-Arten und Revision der Struktur eines Germacranolids. Phytochemistry 19:841–844

  35. Bohlmann F, Ziesche J, Robinson H, King RM (1980b) Neue Amide aus Spilanthes alba. Phytochemistry 19:1535–1537

  36. Bohlmann F, Gerke T, Ahmed M, King RM, Robinson H (1983) Neue N-Isobutylamide aus Heliopsis-Arten. Liebigs Ann Chem 1202–1206

  37. Bohlmann F, Hartono L, Jakupovic J (1985) Highly unsaturated amides from Salmea scandens. Phytochemistry 24:595–596

  38. Boonen J, Baert B, Burvenich C, Blondeel P, De Saeger S, De Spiegeleer B (2010a) LC-MS profiling of N-alkylamides in Spilanthes acmella extract and the transmucosal behaviour of its main bio-active spilanthol. J Pharm Biomed Anal 53:243–249

  39. Boonen J, Baert B, Roche N, Burvenich C, De Spiegeleer B (2010b) Transdermal behaviour of the N-alkylamide spilanthol (affinin) from Spilanthes acmella (Compositae) extracts. J Ethnopharmacol 127:77–84

  40. Boonen J, Bronselaer A, Nielandt J, Veryser L, De Tré G, De Spiegeleer B (2012a) Alkamid database: chemistry, occurrence and functionality of plant N-alkylamides. J Ethnopharmacol 142:563–590

  41. Boonen J, Sharma V, Dixit VK, Burvenich C, De Spiegeleer B (2012b) LC-MS N-alkylamide profiling of an ethanolic Anacyclus pyrethrum root extract. Planta Med 78:1787–1795

  42. Bowden K, Ross WJ (1963) The local anaesthetic in Fagara xanthoxyloides. J Chem Soc 3503–3505

  43. Bryant BP, Mezine I (1999) Alkylamides that produce tingling paresthesia activate tactile and thermal trigeminal neurons. Brain Res 842:452–460

  44. Buchheim R (1876) Ueber die pharmakologische Gruppe des Piperins. Arch Exp Pathol Pharm 5:455–462

  45. Burden RS, Crombie L (1969) Amides of vegetable origin Part XII. A new series of alka-2,4-dienoic tyramin-amides from Anacyclus pyrethrum D.C. (Compositae). J Chem Soc C Org 19:2477–2481

  46. Cahoon EB, Lindqvist Y, Schneider G, Shanklin J (1997) Redesign of soluble fatty acid desaturases from plants for altered substrate specificity and double bond position. Proc Natl Acad Sci USA 94:4872–4877

  47. Cahoon EB, Carlson TJ, Ripp KG, Schweiger BJ, Cook GA, Hall SE, Kinney AJ (1999) Biosynthetic origin of conjugated double bonds: production of fatty acid components of high-value drying oils in transgenic soybean embryos. Proc Natl Acad Sci USA 96:12935–12940

  48. Cahoon EB, Ripp KG, Hall SE, Kinney AJ (2001) Formation of conjugated Δ8, Δ10-double bonds by Δ12-oleic-acid desaturase-related enzymes. J Biol Chem 276:2637–2643

  49. Cambie RC, Gardner JN, Jones ERH, Lowe G, Read G (1963) Chemistry of the higher fungi. Part XIV. Polyacetylenic metabolites of Poria sinuosa Fr. J Chem Soc 2056–2064

  50. Cariño-Cortés R, Gayosso-De-Lucio JA, Ortiz MI, Sánchez-Gutiérrez M, García-Reyna PB, Cilia-López VG, Pérez-Hernández N, Moreno E, Ponce-Monter H (2010) Antinociceptive, genotoxic and histopathological study of Heliopsis longipes S. F. Blake in mice. J Ethnopharmacol 130:216–221

  51. Casado M, Ortega MG, Peralta M, Agnese AM, Caprera JL (2009) Two new alkamides from roots of Acmella decumbens. Nat Prod Res 23:1298–1303

  52. Castro KNC, Lima DF, Vasconcelos LC, Leite JRSA, Santos RC, Paz Neto AA, Costa-Júnior LM (2014) Acaricide activity in vitro of Acmella oleracea against Rhipicephalus microplus. Parasitol Res 113:3697–3701

  53. Chaaib F, Queiroz EF, Ndjoko K, Diallo D, Hostettmann K (2003) Antifungal and antioxidant compounds from the root bark of Fagara zanthoxyloides. Planta Med 69:316–320

  54. Chan GW, Berry D, DeBrosse CW, Hemling ME, MacKenzie-LoCasto L, Offen PH, Westley JW (1993) Conioidines A and B, novel DNA-interacting pyrrolidines from Chamaesaracha conioides. J Nat Prod 56:708–713

  55. Chen IS, Chen TL, Lin WY, Tsai IL, Chen YC (1999) Isobutylamides from the fruit of Zanthoxylum integrifoliolum. Phytochemistry 52:357–360

  56. Chen Y, Fu T, Tao T, Yang J, Chang Y, Wang M, Kim L, Qu L, Cassady J, Scalzo R, Wang X (2005) Macrophage activating effects of new alkamides from the roots of Echinacea species. J Nat Prod 68:773–776

  57. Chen JJ, Chung CY, Hwang TL, Chen JF (2009) Amides and benzenoids from Zanthoxylum ailanthoides with inhibitory activity on superoxide generation and elastase release by neutrophils. J Nat Prod 72:107–111

  58. Christensen LP (1992) Acetylenes and related compounds in Anthemideae. Phytochemistry 31:7–49

  59. Christensen LP, Lam J (1991) Acetylenes and related compounds in Heliantheae. Phytochemistry 30:11–49

  60. Christensen KB, Petersen RK, Petersen S, Kristiansen K, Christensen LP (2009) Activation of PPARγ by metabolites from the flowers of purple coneflower (Echinacea purpurea). J Nat Prod 72:933–937

  61. Christodoulopoulou L, Tsoukatou M, Tziveleka LA, Vagias C, Petrakis PV, Roussis V (2005) Piperidinyl amides with insecticidal activity from the maritime plant Otanthus maritimus. J Agric Food Chem 53:1435–1439

  62. Cilia-López VG, Juárez-Flores BI, Aguirre-Rivera JR, Reyes-Agüero JA (2010) Analgesic activity of Heliopsis longipes and its effect on the nervous system. Pharm Biol 48:195–200

  63. Clifford LJ, Nair MG, Rana J, Dewitt DL (2002) Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench. Phytomedicine 9:249–253

  64. Cortez-Espinosa N, Aviña-Verduzco JA, Ramírez-Chávez E, Molina-Torres J, Ríos-Chávez P (2011) Valine and phenylalanine as precursors in the biosynthesis of alkamides in Acmella radicans. Nat Prod Commun 6:857–861

  65. Crombie L (1954) Isolation and structure of neo-herculin from Zanthoxylum clava-herculis L. Nature 174:833

  66. Crombie L (1955a) Amides of vegetable origin. Part III. Structure and stereochemistry of neoherculin. J Chem Soc 995–998

  67. Crombie L (1955b) Amides of vegetable origin. Part IV. The nature of pellitorine and anacyclin. J Chem Soc 999–1006

  68. Crombie L, Tayler JL (1957) Amides of vegetable origin. Part VIII. The constitution and configuration of the sanshoöls. J Chem Soc 2760–2766

  69. Crombie L, Krasinski AHA, Manzoor-i-Khuda M (1963) Amides of vegetable origin. Part X. The stereochemistry and synthesis of affinin. J Chem Soc 4970–4976

  70. Cruz I, Cheetham JJ, Arnason JT, Yack JE, Smith ML (2014) Alkamides from Echinacea disrupt the fungal cell wall-membrane complex. Phytomedicine 21:435–442

  71. Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O´Connell MA (1999) Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp. Plant Sci 148:47–57

  72. Dawid C, Henze A, Frank O, Glabasnia A, Rupp M, Büning K, Orlikowski D, Bader M, Hofmann T (2012) Structural and sensory characterization of key pungent and tingling compounds from black pepper (Piper nigrum L.). J Agric Food Chem 60:2884–2895

  73. Déciga-Campos M, Rios MY, Aguilar-Guadarrama AB (2010) Antinociceptive effect of Heliopsis longipes extract and affinin in mice. Planta Med 76:665–670

  74. Déciga-Campos M, Arriaga-Alba M, Ventura-Martínez R, Aguilar-Guadarrama B, Rios MY (2012) Pharmacological and toxicological profile of extract from Heliopsis longipes and affinin. Drug Dev Res 73:130–137

  75. Dembitsky VM, Shkrob I, Rozentsvet OA (2000) Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum. Phytochemistry 54:965–967

  76. Devkota KP, Wilson J, Henrich CJ, McMahon JB, Reilly KM, Beutler JA (2013) Isobutylhydroxyamides from the pericarp of Nepalese Zanthoxylum armatum inhibit NF1-defective tumor cell line growth. J Nat Prod 76:59–63

  77. Dhar KL, Atal CK (1967) Occurrence of N-isobutyldeca-trans-2-trans-4-dienamide in Piper longum Linn. and Piper peepuloides Royle. Indian J Chem 5:588–589

  78. Dietz B (2002) Untersuchungen zu den Inhaltsstoffen von Echinacea atrorubens sowie zur Wirkung und Bioverfügbarkeit von Alkamiden. Dissertation, Heinrich-Heine-Universität Düsseldorf

  79. Dietz B, Bauer R (2001) The constituents of Echinacea atrorubens roots and aerial parts. Pharm Biol 39:11–15

  80. Dietz B, Heilmann J, Bauer R (2001) Absorption of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides after oral application of Echinacea purpurea tincture. Planta Med 67:863–864

  81. Do Nascimento JC, De Paula VF, David JM, David JP (2012) Occurrence, biological activities and 13C NMR data of amides from Piper (Piperaceae). Quim Nova 35:2288–2311

  82. Domínguez XA, Sánchez VH, Slim SJ, Jakupovic J, Lehmann L, Bohlmann F (1987) Highly unsaturated amides from Sanvitalia ocymoides. Rev Latinoamer Quim 18:114–115

  83. Doskotch RW, Beal JL (1970) The isolation and identification of the numbing principle in Chrysanthemum anethifolium. Lloydia 33:393–394

  84. Dossou KSS, Devkota KP, Morton C, Egan JM, Lu G, Beutler JA, Moaddel R (2013) Identification of CB1/CB2 ligands from Zanthoxylum bungeanum. J Nat Prod 76:2060–2064

  85. Dunstan WR, Garnett H (1895) Note on the active constituent of the pellitory of medicine. J Chem Soc 67:100–102

  86. Ee GCL, Lim CM, Rahman M, Shaari K, Bong CFJ (2010) Pellitorine, a potential anti-cancer lead compound against HL60 and MCT-7 cell lines and microbial transformation of piperine from Piper nigrum. Molecules 15:2398–2404

  87. Ehrendorfer F, Guo YP (2005) Changes in the circumscription of the genus Achillea (Compositae–Anthemideae) and its subdivision. Willdenowia 35:49–54

  88. Ehrendorfer F, Guo YP (2006) Multidisciplinary studies on Achillea sensu lato (Compositae–Anthemideae): new data on systematics and phylogeography. Willdenowia 36:69–87

  89. Elliott M, Farnham AW, Janes NF, Johnson DM, Pulman DA (1987) Synthesis and insecticidal activity of lipophilic amides. Part 3: influence of chain length and terminal group in N-(2-methylpropyl)-2,4-dienamides. Pestic Sci 18:211–221

  90. Galopin CC, Furrer SM, Goeke A (2004) Pungent and tingling compounds in Asian cuisine. In: Hofmann T, Ho CT, Pickenhagen W (eds) Challenges in taste chemistry and biology, ACS symposium series 867. American Chemical Society, Washington DC

  91. Gamboa-Leon R, Chilton WS (2000) Isobutylamide numbing agents of the toothache grass, Ctenium aromaticum. Biochem Syst Ecol 28:1019–1021

  92. García-Chávez A, Ramírez-Cháves E, Molina-Torres J (2004) El genero Heliopsis (Heliantheae, Asteraceae) en Mexico y las alcamidas presents en sus raíces. Acta Bot Mex 69:115–131

  93. Gerber E (1903) Ueber die chemischen Bestandteile der Parakresse (Spilanthes oleracea, Jacquin). Arch Pharm 241:270–289

  94. Gersdorff WA, Mitlin N (1950) Insecticidal action of American species of Heliopsis. J Econ Entom 43:554–555

  95. Gertsch J (2008) Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system. Planta Med 74:638–650

  96. Gertsch J, Schoop R, Kuenzle U, Suter A (2004) Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett 577:563–569

  97. Gertsch J, Raduner S, Altmann KH (2006) New natural noncannabinoid ligands for cannabinoid type-2 (CB2) receptors. J Recept Signal Transduct Res 26:709–730

  98. Goey AKL, Rosing H, Meijerman I, Sparidans RW, Schellens JHM, Beijnen JH (2012) The bioanalysis of the major Echinacea purpurea constituents dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides in human plasma using LC–MS/MS. J Chromatogr B 902:151–156

  99. Greger H (1977) Anthemideae-chemical review. In: Heywood VH, Harborne JB, Turner BL (eds) The biology and chemistry of the Compositae, vol 2. Academic Press, London

  100. Greger H (1978) Comparative phytochemistry and systematics of Anacyclus. Biochem Syst Ecol 6:11–17

  101. Greger H (1984) Alkamides: structural relationships, distribution and biological activity. Planta Med 50:366–375

  102. Greger H (1985) Vergleichende Phytochemie als biologische Disziplin. Plant Syst Evol 150:1–13

  103. Greger H (1988) Comparative phytochemistry of the alkamides. In: Lam J, Breteler H, Arnason T, Hansen L (eds) Chemistry and biology of naturally-occurring acetylenes and related compounds (NOARC). Elsevier, Amsterdam

  104. Greger H, Hofer O (1984) On the pungent principle of Matricaria pubescens. Phytochemistry 23:1173–1174

  105. Greger H, Hofer O (1987) Highly unsaturated isopentyl amides from Achillea wilhelmsii. J Nat Prod 50:1100–1107

  106. Greger H, Hofer O (1989) Polyenoic acid piperideides and other alkamides from Achillea millefolium. Phytochemistry 28:2363–2368

  107. Greger H, Werner A (1990) Comparative HPLC analyses of alkamides within the Achillea millefolium group. Planta Med 56:482–486

  108. Greger H, Grenz M, Bohlmann F (1981) Amides from Achillea species and Leucocyclus formosus. Phytochemistry 20:2579–2581

  109. Greger H, Grenz M, Bohlmann F (1982) Piperidides and other amides from Achillea species. Phytochemistry 21:1071–1074

  110. Greger H, Zdero C, Bohlmann F (1983) Weitere ungesättige Amide aus Achillea-Arten. Liebigs Ann Chem 1194–1201

  111. Greger H, Zdero C, Bohlmann F (1984) Pyrrolidine and piperidine amides from Achillea. Phytochemistry 23:1503–1505

  112. Greger H, Hofer O, Werner A (1985) New amides from Spilanthes oleracea. Monatsh Chem 116:273–277

  113. Greger H, Hofer O, Werner A (1987a) Biosynthetically simple C18-alkamides from Achillea species. Phytochemistry 26:2235–2242

  114. Greger H, Zdero C, Bohlmann F (1987b) Pyrrole amides from Achillea ageratifolia. Phytochemistry 26:2289–2291

  115. Greger H, Zechner G, Hofer O, Vajrodaya S (1996) Bioactive amides from Glycosmis species. J Nat Prod 59:1163–1168

  116. Gulland JM, Hopton GU (1930) Pellitorine, the pungent principle of Anacyclus pyrethrum. J Chem Soc (resumed) 6–11

  117. Gupta OP, Gupta SC, Dhar KL, Atal CK (1976) Structure of a new amide, filfiline, isolated from Piper officinarum. Indian J Chem 14B:912–913

  118. Hajdu Z, Nicolussi S, Rau M, Lorántfy L, Forgo P, Hohmann J, Csupor D, Gertsch J (2014) Identification of endocannabinoid system-modulating N-alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii. J Nat Prod 77:1663–1669

  119. Hashimoto K, Satoh K, Kase Y, Ishige A, Kubo M, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K, Nakamura T (2001) Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated gastrointestinal tract. Planta Med 67:179–181

  120. Hatano T, Inada K, Ogawa T, Ito H, Yoshida T (2004) Aliphatic acid amides of the fruits of Zanthoxylum piperitum. Phytochemistry 65:2599–2604

  121. Hernández I, Márquez L, Martínez I, Dieguez R, Delporte C, Prieto S, Molino-Torres J, Garrido G (2009) Anti-inflammatory effects of ethanolic extract and alkamides-derived from Heliopsis longipes roots. J Ethnopharmacol 124:649–652

  122. Herz W, Kulanthaivel P (1985) An amide from Salmea scandens. Phytochemistry 24:173–174

  123. Hinz B, Woelkart K, Bauer R (2007) Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells. Biochem Biophys Res Commun 360:441–446

  124. Hofer O, Greger H, Robien W, Werner A (1986) 13C NMR and 1H lanthanide induced shifts of naturally occurring alkamides with cyclic amide moieties—amides from Achillea falcata. Tetrahedron 42:2707–2716

  125. Hofer O, Zechner G, Vajrodaya S, Lutz G, Greger H (1995) New anthranilic and methylsulfonylpropenoic acid amides from Thai Glycosmis species. Liebigs Ann 1789–1794

  126. Hohmann J, Rédei D, Forgo P, Szabó P, Freund TF, Haller J, Bojnik E, Benyhe, S (2011) Alkamides and a neolignan from Echinacea purpurea and the interaction of alkamides with G-protein-coupled cannabinoid receptors. Phytochemistry 72:1848–1853

  127. Hou CC, Chen CH, Yang NS, Chen YP, Lo CP, Wang SY, Tien YJ, Tsai PW, Shyur LF (2010) Comparative metabolomics approach coupled with cell- and gene-based assays for species classification and anti-inflammatory bioactivity validation of Echinacea plants. J Nutr Biochem 21:1045–1059

  128. Hou CC, Huang CC, Shyur LF (2011) Echinacea alkamides prevent lipopolysaccharide/d-galactosamine-induced acute hepatic injury through JNK pathway-mediated HO-1 expression. J Agric Food Chem 59:11966–11974

  129. Huang S, Zhao L, Zhou XL, Ying M, Wang CJ, Weng J (2012) New alkylamides from pericarps of Zanthoxylum bungeanum. Chin Chem Lett 23:1247–1250

  130. Iseli V, Potterat O, Hagmann L, Egli J, Hamburger M (2007) Characterization of the pungent principles and the essential oil of Zanthoxylum schinifolium pericarp. Pharmazie 62:396–400

  131. Jacobson M (1948) Herculin, a pungent insecticidal constituent of southern prickly ash bark. J Amer Chem Soc 70:4234–4237

  132. Jacobson M (1949) The structure of pellitorine. J Amer Chem Soc 71:366–367

  133. Jacobson M (1951) Constituents of Heliopsis species. I. Scabrin, an insecticidal amide from the roots of H. scabra Dunal. J Amer Chem Soc 73:100–103

  134. Jacobson M (1954) Occurrence of a pungent insecticidal principle in American coneflower roots. Science 120:1028–1029

  135. Jacobson M (1957a) The structure of spilanthol. Chem Ind (London) 50–51

  136. Jacobson M (1957b) Constituents of Heliopsis species. V. Heliopsin, a second insecticidal amide from the roots of H. helianthoides var. scabra. J Amer Chem Soc 79:356–358

  137. Jager H, Meinel L, Dietz B, Lapke C, Bauer R, Merkle HP, Heilmann J (2002) Transport of alkamides from Echinacea species through Caco-2 monolayers. Planta Med 68:469–471

  138. Jakupovic J, Schuster A, Bohlmann F, King RM, Robinson H (1986) New lignans and isobutylamides from Heliopsis buphthalmoides. Planta Med 52:18–20

  139. Jang KH, Chang YH, Kim DD, Oh KB, Oh U, Shin J (2008) New polyunsaturated fatty acid amides isolated from the seeds of Zanthoxylum piperitum. Arch Pharm Res 31:569–572

  140. Jente R, Richter E (1976) Zur Biosynthese des Dehydromatricariaesters. Phytochemistry 15:1673–1679

  141. Jente R, Bonnet PH, Bohlmann F (1972) Über die Inhaltsstoffe von Anacyclus pyrethrum DC. Chem Ber 105:1694–1700

  142. Jiang LY, Chen JJ, He S, Sun CR (2009) High-throughput structural elucidation of amides in Mallotus lianus Croiz plant materials by LC–ESI–MS–MS. Chromatographia 70:439–445

  143. Johns T, Graham K, Towers GHN (1982) Molluscicidal activity of affinin and other isobutylamides from the Asteraceae. Phytochemistry 21:2737–2738

  144. Jondiko IJ (1986) A mosquito larvicide in Spilanthes mauritiana. Phytochemistry 25:2289–2290

  145. Kadir HA, Zakaria MB, Kechil AA, Azirun MS (1989) Toxicity and electrophysiological effects of Spilanthes acmella Murr. extracts on Periplaneta americana. Pestic Sci 25:329–335

  146. Kashiwada Y, Ito C, Katagiri H, Mase I, Komatsu K, Namba T, Ikeshiro Y (1997) Amides of the fruit of Zanthoxylum ssp. Phytochemistry 44:1125–1127

  147. Kehie M, Kumaria S, Tandon P, Ramchiary N (2015) Biotechnological advances on in vitro capsaicinoids biosynthesis in Capsicum: a review. Phytochem Rev 14:189–201

  148. Keipert R (2009) Acmella ciliata (H.B.K.) Cassini. Phytochemische und enzymatische Untersuchungen, galenische Präformulierungen. Dissertation, Freie Universität Berlin

  149. Keipert R, Melzig MF (2009) Acmella ciliata (H.B.K.) Cassini. Z Phytother 30:44–50

  150. Kikuzaki H, Kawabata M, Ishida E, Akazawa Y, Takei Y, Nakatani N (1993) LC–MS Analysis and structural determination of new amides from Javanese long pepper (Piper retrofractum). Biosci Biotech Biochem 57:1329–1333

  151. Kim SC, Chapman KD, Blancaflor EB (2010) Fatty acid amide lipid mediators in plants. Plant Sci 178:411–419

  152. Koul SK, Taneja SC, Agarwal VK, Dhar KL (1988) Minor amides of Piper species. Phytochemistry 27:3523–3527

  153. Kubo I, Matsumoto T, Klocke JA, Kamikawa T (1984) Molluscicidal and insecticidal activities of isobutylamides isolated from Fagara macrophylla. Experientia 40:340–341

  154. Kubo M, Ishii R, Ishino Y, Harada K, Matsui N, Akagi M, Kato E, Hosoda S, Fukuyama Y (2013) Evaluation of constituents of Piper retrofractum fruits on neurotrophic activity. J Nat Prod 76:769–773

  155. Kuropka G, Glombitza KW (1987) Further polyenic and polyynic carboxamides and sesamin from Achillea ptarmica. Planta Med 53:440–442

  156. Kuropka G, Koch M, Glombitza KW (1986) Säureamide aus Achillea ptarmica. Planta Med 52:244–245

  157. LaForge FB, Haller HL, Sullivan WN (1942) The presence of an insecticidal principle in the bark of southern prickly ash. J Am Chem Soc 64:187

  158. LaLonde RT, Wong CF, Hofstead SJ, Morris CD, Gardner LC (1980) N-(2-Methylpropyl)-(E, E)-2,4-decadienamide. A mosquito larvicide from Achillea millefolium L. J Chem Ecol 6:35–48

  159. LaLone CA, Hammer KDP, Wu L, Bae J, Leyva N, Liu Y, Solco AKS, Kraus GA, Murphy PA, Wurtele ES, Kim OK, Seo KII, Widrlechner MP, Birt DF (2007) Echinacea species and alkamides inhibit prostaglandin E2 production in RAW264.7 mouse macrophage cells. J Agric Food Chem 55:7314–7322

  160. Lazarević J, Radulović N, Zlatković B, Palić R (2010) Composition of Achillea distans Willd. subsp. distans root essential oil. Nat Prod Res 24:718–731

  161. Leitão da-Cunha EV, de Oliveira Chaves MC (2001) Two amides from Piper tuberculatum fruits. Fitoterapia 72:197–199

  162. Lennertz RC, Tsunozaki M, Bautista DM, Stucky CL (2010) Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool. J Neurosci 30:4353–4361

  163. Leonard AE, Pereira SL, Sprecher H, Huang YS (2004) Elongation of long-chain fatty acids. Prog Lipid Res 43:36–54

  164. Ley JP, Krammer G, Looft J, Reinders G, Bertram HJ (2006a) Structure-activity relationships of trigeminal effects for artificial and naturally occurring alkamides related to spilanthol. In: Bredie WLP, Petersen MA (eds) Flavour science: recent advances and trends. Elsevier, Amsterdam

  165. Ley JP, Blings M, Krammer G, Reinders G, Schmidt CO, Bertram HJ (2006b) Isolation and synthesis of acmellonate, a new unsaturated long chain 2-ketolester from Spilanthes acmella. Nat Prod Res 20:798–804

  166. Li GP, Shen BC, Zhao JF, Yang XD, Li L (2007) Two new alkamides from Spilanthes callimorpha. J Integr Plant Biol 49:1608–1610

  167. Li K, Zhu W, Fu Q, Ke Y, Jin Y, Liang X (2013) Purification of amide alkaloids from Piper longum L. using preparative two-dimensional normal-phase liquid chromatography × reversed-phase liquid chromatography. Analyst 138:3313–3320

  168. Likhitwitayawuid K, Ruangrungsi N, Lange GL, Decicco CP (1987) Structural elucidation and synthesis of new components isolated from Piper sarmentosum (Piperaceae). Tetrahedron 43:3689–3694

  169. Loder JW, Moorhouse A, Russell GB (1969) Tumour inhibitory plants. Amides of Piper novae-hollandiae (Piperaceae). Aust J Chem 22:1531–1538

  170. López-Bucio J, Acevedo-Hernández G, Ramírez-Chávez E, Molina-Torres J, Herrera-Estrella L (2006) Novel signals for plant development. Curr Opin Plant Biol 9:523–529

  171. López-Martínez S, Aguilar-Guadarrama B, Rios MY (2011) Minor alkamides from Heliopsis longipes S.F. Blake (Asteraceae) fresh roots. Phytochem Lett 4:275–279

  172. Loureiro-Rosario S, da Silva AJR, Parente JP (1996) Alkamides from Cissampelos glaberrima. Planta Med 62:376–377

  173. Mahringer A, Ardjomand-Woelkart K, Bauer R, Fricker G, Efferth T (2013) Alkamides from Echinacea angustifolia interact with P-glycoprotein of primary brain capillary endothelial cells isolated from porcine brain blood vessels. Planta Med 79:214–218

  174. Martin R, Becker H (1984) Spilanthol-related amides from Acmella ciliata. Phytochemistry 23:1781–1783

  175. Martin R, Becker H (1985) Amides and other constituents from Acmella ciliata. Phytochemistry 24:2295–2300

  176. Matovic NJ, Hayes PY, Penman K, Lehmann RP, DeVoss JJ (2011) Polyunsaturated alkyl amides from Echinacea: synthesis of diynes, enynes, and dienes. J Org Chem 76:4467–4481

  177. Matthias A, Blanchfield JT, Penman KG, Toth I, Lang CS, DeVoss JJ, Lehmann RP (2004) Permeability studies of alkylamides and caffeic acid conjugates from echinacea using a Caco-2-cell monolayer model. J Clin Pharm Ther 29:7–13

  178. Menozzi-Smarrito C, Riera CE, Munari C, Le Coutre J, Robert F (2009) Synthesis and evaluation of new alkylamides derived from α-hydroxysanshool, the pungent molecule in Szechuan pepper. J Agric Food Chem 57:1982–1989

  179. Merali S, Binns S, Paulin-Levasseur M, Ficker C, Smith M, Baum B, Brovelli E, Arnason JT (2003) Antifungal and anti-inflammatory activity oft he genus Echinacea. Pharm Biol 41:412–420

  180. Mester I (1983) Structural diversity and distribution of alkaloids in the Rutales. In: Waterman PG, Grundon MF (eds) Chemistry and chemical taxonomy of the Rutales. Academic Press, London

  181. Minto RE, Blacklock BJ (2008) Biosynthesis and function of polyacetylenes and allied natural products. Prog Lipid Res 47:233–306

  182. Mizutani K, Fukunaga Y, Tanaka O, Takasugi N, Saruwatari YI, Fuwa T, Yamauchi T, Wang J, Jia MR, Li FY, Ling YK (1988) Amides from Huajiao, pericarps of Zanthoxylum bungeanum MAXIM. Chem Pharm Bull 36:2362–2365

  183. Molina-Torres J, Salgado-Garciglia R, Ramírez-Chávez E, Del Rio RE (1996) Purely oleofinic alkamides in Heliopsis longipes and Acmella (Spilanthes oppositifolia). Biochem Syst Ecol 24:43–47

  184. Molina-Torres J, García-Chávez A, Ramírez-Chávez E (1999) Antimicrobial properties of alkamides present in flavouring plants traditionally used in Mesoamerica: affinin and capsaicin. J Ethnopharmacol 64:241–248

  185. Molina-Torres J, Salazar-Cabrera CJ, Armenta-Salinas C, Ramírez-Chávez E (2004) Fungistatic and bacteriostatic activities of alkamides from Heliopsis longipes roots: affinin and reduced amides. J Agric Food Chem 52:4700–4704

  186. Moreno SC, Carvalho GA, Picanço MC, Morais EGF, Pereira RM (2012) Bioactivity of compounds from Acmella oleracea against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and selectivity to two non-target species. Pest Manag Sci 68:386–393

  187. Morikawa T, Matsuda H, Yamaguchi I, Pongpiriyadacha Y, Yoshikawa M (2004) New amides and gastroprotective constituents from the fruit of Piper chaba. Planta Med 70:152–159

  188. Morquecho-Contreras A, Méndez-Bravo A, Pelagio-Flores R, Raya-González J, Ortíz-Castro R, López-Bucio J (2010) Characterization of drr1, an alkamide-resistant mutant of Arabidopsis, reveals an important role for small lipid amides in lateral root development and plant senescence. Plant Physiol 152:1659–1673

  189. Muhammad I, Zhao J, Dunbar DC, Khan IA (2002) Constituents of Lepidium meyenii ‘maca’. Phytochemistry 59:105–110

  190. Müller-Jakic B, Breu W, Pröbstle A, Redl K, Greger H, Bauer R (1994) In vitro inhibition of cylclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achillea species. Planta Med 60:37–40

  191. Murayama Y, Shinozaki K (1931) Über den scharfen Bestandteil von Xanthoxylum piperitum D. C. J Pharm Soc Jpn 51:379–384

  192. Nakatami N, Nagashima M (1992) Pungent alkamides from Spilanthes acmella L. var. oleracea Clarke. Biosci Biotech Biochem 56:759–762

  193. Narui T, Takeuchi M, Ishii R, Ishida T, Okuyama T (1995) Studies on the constituents of Piper hancei of spice from Okinawa. Nat Med 49:438–441

  194. Navarrete A, Hong E (1996) Anthelminthic properties of alpha-sanshool from Zanthoxylum liebmannianum. Planta Med 62:250–251

  195. Ndom JC, Mbafor JT, Meva´a LM, Kakam Z, Phanuel AS, Ndongo E, Harwood LM, Mpondo TN (2010) New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae). Phytochem Lett 3:201–206

  196. Obst K, Paetz S, Backes M, Reichelt KV, Ley JP, Engel KH (2013) Evaluation of unsaturated alkanoic acid amides as maskers of epigallocatechin gallate astringency. J Agric Food Cem 61:4242–4249

  197. Ogura M, Cordell GA, Quinn ML, Leon C, Benoit PS, Soejarto DD, Farnsworth NR (1982) Ethnopharmacologic studies I: rapid solution to a problem—oral use of Heliopsis longipes—by means of a multidisciplinary approach. J Ethnopharmacol 64:215–219

  198. Ospina de Nigrinis LS, Olarte Caro J, Nuñez Olarte E (1986) Estudio fitofarmacologico de la fraccion liposoluble de las flores de la Spilanthes americana (Mutis) Parte I: Estudio fitoquimico. Rev Colomb Cienc Quim-Farmac 15:37–47

  199. Parmar VS, Jain SC, Bisht KS, Jain R, Taneja P, Jha A, Tyagi OD, Prasad AK, Wengel J, Olsen CE, Boll PM (1997) Phytochemistry of the genus Piper. Phytochemistry 46:597–673

  200. Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, Altmann KH, Gertsch J (2006) Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 281:14192–14206

  201. Raduner S, Bisson W, Abagyan R, Altmann KH, Gertsch J (2007) Self-assembling cannabinomimetics: supramolecular structures of N-alkyl amides. J Nat Prod 70:1010–1015

  202. Rahman MAA, Cho SC, Song J, Mun HT, Moon SS (2007) Dendrazawaynes A and B, antifungal polyacetylenes from Dendranthema zawadskii (Asteraceae). Planta Med 73:1089–1094

  203. Ramírez-Chávez E, López-Bucio J, Herrera-Estrella L, Molina-Torres J (2004) Alkamides isolated from plants promote growth and alter root development in Arabidopsis. Plant Physiol 134:1058–1068

  204. Ramírez-Noya D, González-Elizondo MS, Molina-Torres J (2011) Heliopsis suffruticosa (Compositae, Heliantheae), una nueva especie des occidente de Zacatecas. Acta Bot Mex 97:39–47

  205. Ramsewak RS, Erickson AJ, Nair MG (1999) Bioactive N-isobutylamides from the flower buds of Spilanthes acmella. Phytochemistry 51:729–732

  206. Reisch J, Hussain RA, Adesina SK, Szendrei K (1985) A new amide from Evodia hupehensis fruit hull. J Nat Prod 48:862–863

  207. Riemer B, Hofer O, Greger H (1997) Tryptamine derived amides from Clausena indica. Phytochemistry 45:337–341

  208. Rios MY (2012) Natural alkamides: pharmacology, chemistry and distribution. In: Vallisuta O (ed) Drug discovery research in pharmacognosy. InTech, Rijeka

  209. Rios MY, Olivo HF (2014) Natural and synthetic alkamides: applications in pain therapy. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 43. Elsevier, Amsterdam

  210. Rios MY, Aguilar-Guadarrama AB, Gutiérrez MdC (2007) Analgesic activity of affinin, an alkamide from Heliopsis longipes (Compositae). J Ethnopharmacol 110:364–367

  211. Rios-Chavez P, Ramirez-Chavez E, Armenta-Salinas C, Molina-Torres L (2003) Acmella radicans var. radicans: in vitro culture establishment and alkamide content. In Vitro Cell Dev Biol Plant 39:37–41

  212. Saadali B, Boriky D, Blaghen M, Vanhaelen M, Talbi M (2001) Alkamides from Artemisia dracunculus. Phytochemistry 58:1083–1086

  213. Sasagawa M, Cech NB, Gray DE, Elmer GW, Wenner CA (2006) Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells. Int Immunopharmacol 6:1214–1221

  214. Shanklin J, Cahoon EB (1998) Desaturation and related modifications of fatty acids. Annu Rev Plant Physiol Plant Mol Biol 49:611–641

  215. Sharma V, Thakur M, Chauhan NS, Dixit VK (2009) Evaluation of the anabolic, aphrodisiac and reproductive activity of Anacyclus pyrethrum DC in male rats. Sci Pharm 77:97–110

  216. Sharma V, Thakur M, Chauhan NS, Dixit VK (2010) Effects of petroleum ether extract of Anacyclus pyrethrum DC. on sexual behavior in male rats. J Chin Integr Med 8:767–773

  217. Sharma V, Boonen J, Chauhan NS, Thakur M, DeSpiegeleer B, Dixit VK (2011) Spilanthes acmella ethanolic extract: LC-MS alkylamide profiling and its effects on sexual behavior in male rats. Phytomedicine 18:1161–1169

  218. Sharma V, Boonen J, De Spiegeleer B, Dixit VK (2013) Androgenic and spermatogenic activity of alkamide-rich ethanol solution extract of Anacyclus pyrethrum DC. Phytother Res 27:99–106

  219. Shibuya H, Takeda Y, Zhang RS, Tong RX, Kitagawa I (1992) Indonesian medicinal plants III. On the constituents of the bark of Fagara rhetza (Rutaceae). (1): alkaloids, phenylpropanoids, and acid amide. Chem Pharm Bull 40:2325–2330

  220. Siddiqui BS, Gulzar T, Mahmood A, Begum S, Khan B, Afshan F (2004) New insecticidal amides from petroleum ether extract of dried Piper nigrum L. whole fruits. Chem Pharm Bull 52:1349–1352

  221. Simas NK, Da Dellamora ECL, Schripsema J, Salgueiro Lage CL, de Oliveira Filho AM, Wessjohann L, Porzel A, Kuster RM (2013) Acetylenic 2- phenylethylamides and new isobutylamides from Acmella oleracea (L.) R. K. Jansen, a Brazilian spice with larvicidal activity on Aedes aegypti. Phytochem Lett 6:67–72

  222. Singh J, Dhar KL, Atal CK (1971) Studies on the genus Piper-XII. Structure of trichonine, a new N-pyrrolidinyl eicosa-trans-2, trans-4 dienamide. Tetrahedron Lett 2119–2120

  223. Sittie AA, Lemmich E, Olsen CE, Hviid L, Christensen SB (1998) Alkamides from Phyllanthus fraternus. Planta Med 64:192–193

  224. Spelman K, Depoix D, McCray M, Mouray E, Grellier P (2011) The traditional medicine Spilanthes acmella, and the alkylamides spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, demonstrate in vitro and in vivo antimalarial activity. Phytother Res 25:1098–1101

  225. Strunz GM (2000) Unsaturated amides from Piper species (Piperaceae). In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 24. Elsevier, Amsterdam

  226. Sugai E, Morimitsu Y, Iwasaki Y, Morita A, Watanabe T, Kubota K (2005a) Pungent qualities of sanshool-related compounds evaluated by a sensory test and activation of rat TRPV1. Biosci Biotechnol Biochem 69:1951–1957

  227. Sugai E, Morimitsu Y, Kubota K (2005b) Quantitative analysis of sanshool compounds in Japanese pepper (Xanthoxylum piperitum DC.) and their pungent characteristics. Biosci Biotechnol Biochem 69:1958–1962

  228. Sun C, Pei S, Pan Y, Shen Z (2007) Rapid structural determination of amides in Piper longum by high-performance liquid chromatography combined with ion trap mass spectrometry. Rapid Commun Mass Spectrom 21:1497–1503

  229. Tackie AN, Dwuma-Badu D, Ayim JSK, ElSohly HN, Knapp JE, Slatkin DJ, Schiff PL Jr (1975) N-Isobutyloctadeca-trans-2-trans-4-dienamide: a new constituent of Piper guineense. Phytochemistry 14:1888–1889

  230. Tang GH, Chen DM, Qiu BY, Sheng L, Wang YH, Hu GW, Zhao FW, Ma LJ, Wang H, Huang QQ, Xu JJ, Long CL, Li J (2011) Cytotoxic amide alkaloids from Piper boehmeriaefolium. J Nat Prod 74:45–49

  231. Thomsen MO, Fretté XC, Christensen KB, Christensen LB, Grevsen K (2012) Seasonal variations in the concentrations of lipophilic compounds and phenolic acids in the roots of Echinacea purpurea and Echinacea pallida. J Agric Food Chem 60:12131–12141

  232. Tofern B, Mann P, Kaloga M, Jenett-Siems K, Witte L, Eich E (1999) Aliphatic pyrrolidine amides from two tropical convolvulaceous species. Phytochemistry 52:1437–1441

  233. Tsao R, Attygalle AB, Schroeder FC, Marvin CH, McGarvey BD (2003) Isobutylamides of unsaturated fatty acids from Chrysanthemum morifolium associated with host-plant resistance against the western flower thrips. J Nat Prod 66:1229–1231

  234. Uttaro AD (2006) Biosynthesis of polyunsaturated fatty acids in lower eukaryotes. IUBMB Life 58:563–571

  235. Veryser L, Taevernier L, Roche N, Peremans K, Burvenich C, De Spiegeleer B (2014) Quantitative transdermal behavior of pellitorine from Anacyclus pyrethrum extract. Phytomedicine 21:1801–1807

  236. Wagner H, Breu W, Willer F, Wierer M, Remiger P, Schwenker G (1989) In vitro inhibition of arachidonate metabolism by some alkamides and prenylated phenols. Planta Med 55:566–567

  237. Wang Y, Wang Y, McNeil B, Harvey LM (2007) Maca: an Andean crop with multi-pharmacological functions. Food Res Int 40:783–792

  238. Wansi JD, Nwozo SO, Mbaze LM, Devkota KP, Moladje SMD, Fomum ZT, Sewald N (2009) Amides from the stem bark of Fagara macrophylla. Planta Med 75:517–521

  239. Wei K, Li W, Koike K, Pei Y, Chen Y, Nikaido T (2004) New amide alkaloids from the roots of Piper nigrum. J Nat Prod 67:1005–1009

  240. Winterfeldt E (1963) Strukturaufklärung und Synthese einer Thiophenverbindung aus Chrysanthemum frutescens L. Chem Ber 96:3349–3358

  241. Woelkart K, Bauer R (2007) The role of alkamides as an active principle of Echinacea. Planta Med 73:615–623

  242. Woelkart K, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R (2005) The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta Med 71:701–705

  243. Woelkart K, Frye RF, Derendorf H, Bauer R, Butterweck V (2009) Pharmacokinetics and tissue distribution of dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides after oral administration in rats. Planta Med 75:1306–1313

  244. Xiong QB, Shi DW, Yamamoto H, Mizuno M (1997) Alkylamides from pericarps of Zanthoxylum bungeanum. Phytochemistry 46:1123–1126

  245. Yang X (2008) Aroma constituents and alkylamides of red and green Huajiao (Zanthoxylum bungeanum and Zanthoxylum schinifolium). J Agric Food Chem 56:1689–1696

  246. Yasuda I, Takeya K, Itokawa H (1980) The geometric structure of spilanthol. Chem Pharm Bull 28:2251–2253

  247. Yasuda I, Takeya K, Itokawa H (1981a) Structures of amides from Asiasarum heterotropoides Maek. var. mandshuricum Maek. Chem Pharm Bull 29:564–566

  248. Yasuda I, Takeya K, Itokawa H (1981b) Two new pungent principles isolated from the pericarps of Zanthoxylum ailanthoides. Chem Pharm Bull 29:1791–1793

  249. Yasuda I, Takeya K, Itokawa H (1982) Distribution of unsaturated aliphatic acid amides in Japanese Zanthoxylum species. Phytochemistry 21:1295–1298

  250. Youssef DTA, van Soest RWM, Fusetani N (2003) Callyspongamide A, a new cytotoxic polyacetylenic amide from the Red Sea sponge Callyspongia fistularis. J Nat Prod 66:861–862

  251. Zdero C, Bohlmann F, King RM, Lander NS (1988) An isobutylamide and beyerene derivatives from Brachycome species. Phytochemistry 27:2984–2985

  252. Zhang F, Chu CH, Xu Q, Fu SP, Hu JH, Xiao HB, Liang XM (2005) A new amide from Asarum forbesii Maxim. J Asian Nat Prod Res 7:1–5

  253. Zhao JP, Muhammad I, Dunbar DC, Mustafa J, Khan IA (2005) New alkamides from Maca (Lepidium meyenii). J Agric Food Chem 53:690–693

  254. Zheng BL, He K, Kim CH, Rogers L, Shao Y, Huang ZY, Lu Y, Yan SJ, Qien LC, Zheng QY (2000) Effect of a lipid extract from Lepidium meyenii on sexual behavior in mice and rats. Urology 55:598–602

Download references

Author information

Correspondence to Harald Greger.

Additional information

Dedicated to my teacher and friend the late Professor Robert Hegnauer, University of Leiden, The Netherlands.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Greger, H. Alkamides: a critical reconsideration of a multifunctional class of unsaturated fatty acid amides. Phytochem Rev 15, 729–770 (2016). https://doi.org/10.1007/s11101-015-9418-0

Download citation


  • Structural diversity
  • Biogenetic trends
  • Chemotaxonomy
  • Biological activities
  • Structure–activity relationships