A Series of Novel Esters of Capsaicin Analogues Catalyzed by Candida antarctica Lipases

다국어 초록 (Multilingual Abstract)

Capsaicin analogues are typically synthetized by condensation of the amide group of vanillylamine with a fatty acid derivative. The enzyme of choice to perform this reaction is Candida antarctica lipase B; however, this enzyme is unable to react with the phenolic substituents of the vanillyl ring. So far, this can only be achieved chemically, resulting in capsaicin esters with higher lipophilicity and less irritation than the parent compound.
In need of searching for new capsaicin derivatives, we investigated the transesterification of the phenolic OH group of capsaicin and several capsaicin analogues by Candida antarctica lipase A (CALA) with vinyl esters.
Capsaicin esters were successfully synthetized with a reaction yield of 80.6% and 57.5% with vinyl butyrate and vinyl laurate, respectively. When the reactions were performed with capsaicin analogues of different acyl chain lengths, CALA exhibited a noticeable transesterification preference for medium-length capsaicin analogues. In an attempt to explore the catalytic limits of CALA, we performed the transesterification of capsaicin from Capsicum oleoresin. The results showed similar transesterification yields to those obtained with semi-pure capsaicin. Within our knowledge, this is the first report to achieve the synthesis of phenolic OH esters of capsaicin and capsaicin analogues by enzymatic means.

참고문헌 (Reference)

1 Ericsson, D. J., "X-ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation" 376 : 109-119, 2008

2 Nilius, B., "Vanilloid receptor TRPV1 in drug discovery: targeting pain and other pathological disorders" John Wiley & Sons, Inc 1-67, 2010

3 Skjøt, M., "Understanding the plasticity of the alpha/beta hydrolase fold : lid swapping on the Candida antarctica lipase B results in chimeras with interesting biocatalytic properties" 10 : 520-527, 2009

4 Appendino, G., "The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination" 48 : 4663-4669, 2005

5 Chen, H., "The molecular basis for lipase stereoselectivity" 102 : 3487-3495, 2018

6 Walpole, C. S. J., "The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin" 37 : 1942-1954, 1994

7 Caterina, M. J., "The capsaicin receptor : a heatactivated ion channel in the pain pathway" 389 : 816-824, 1997

8 Ganesa, S., "Stabilityindicating HPTLC determination of capsaicin in the bulk drug" 21 : 271-275, 2008

9 Chinn, M. S., "Solvent extraction and quantification of capsaicinoids from Capsicum chinense" 89 : 340-345, 2011

10 Jeon, E. Y., "Simultaneous enzyme/whole-cell biotransformation of plant oils into C9 carboxylic acids" 6 : 7547-7553, 2016

11 Cha, H. J., "Simultaneous enzyme/whole-cell biotransformation of C18 ricinoleic acid into (R)-3-hydroxynonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid" 360 : 696-703, 2018

12 Walpole, C. S. J., "Similarities and differences in the structure-activity relationships of capsaicin and resiniferatoxin analogues" 39 : 2939-2952, 1996

13 Dickenson, A. H., "Selective antagonism of capsaicin by capsazepine : evidence for a spinal receptor site in capsaicin-induced antinociception" 104 : 1045-1049, 1991

14 Shumake, S. A., "Repellents to reduce cable gnawing by wild Norway rats" 64 : 1009-1013, 2000

15 Armesto, N., "Regioselective enzymatic acylation of methyl shikimate. Influence of acyl chain length and solvent polarity on enzyme specificity" 67 : 4978-4981, 2002

16 Arimboor, R., "Red pepper(Capsicum annuum)carotenoids as a source of natural food colors : analysis and stability—a review" 52 : 1258-1271, 2015

17 Subagio, A., "Prooxidant activity of lutein and its dimyristate esters in corn triacylglyceride" 81 : 97-102, 2003

18 Balabathula, P., "Potency and stability of intradermal capsaicin : implications for use as a human model of pain in multicenter clinical trials" 4 : 142-, 2014

19 Sricharoen, P., "Phytochemicals in Capsicum oleoresin from different varieties of hot chilli peppers with their antidiabetic and antioxidant activities due to some phenolic compounds" 38 : 629-639, 2017

20 Singh, C. U., "Pharmaceutical compositions comprising capsaicin esters for treating pain and cold sores"

21 Ishihara, K., "One-procedure synthesis of capsiate from capsaicin by lipase-catalyzed dynamic transacylation" 26 : 1337-1340, 2010

22 Melgar-Lalanne, G., "Oleoresins from Capsicum spp.: extraction methods and bioactivity" 10 : 51-76, 2017

23 Özyildiz, F., "Micro-encapsulation of ozonated red pepper seed oil with antimicrobial activity and application to nonwoven fabric" 56 : 168-179, 2013

24 Kobata, K., "Long-chain N-vanillyl-acylamides from Capsicum oleoresin" 58 : 3627-3631, 2010

25 Ema, T., "Lipasecatalyzed kinetic resolution of large secondary alcohols having tetraphenylporphyrin" 39 : 6311-6314, 1998

26 Castillo, E., "Lipase-catalyzed synthesis of pungent capsaicin analogues" 100 : 1202-1208, 2007

27 Kobata, K., "Lipase-catalyzed synthesis of capsaicin analogs by transacylation of capsaicin with natural oils or fatty acid derivatives in n-hexane" 21 : 547-550, 1999

28 Kobata, K., "Lipase-catalyzed synthesis of capsaicin analogs by amidation of vanillylamine with fatty acid derivatives" 20 : 451-454, 1998

29 Reyes-Duarte, D., "Lipase-catalysed synthesis of olvanil in organic solvents" 24 : 2057-2061, 2002

30 From, M., "Lipase catalyzed esterification of lactic acid" 19 : 315-318, 1997

31 Madhumathy, A. P., "Larvicidal efficacy of Capsicum annum against Anopheles stephensi and Culex quinquefasciatus" 44 : 223-226, 2007

32 Kim, H., "Ionic-surfactant-coated Burkholderia cepacia lipase as a highly active and enantioselective catalyst for the dynamic kinetic resolution of secondary alcohols" 50 : 10944-10948, 2011

33 Bae, H., "Influence of extraction solvents on antioxidant activity and the content of bioactive compounds in non-pungent peppers" 67 : 120-128, 2012

34 Woo, J. M., "Improving catalytic activity of the Baeyer–Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of(Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid" 8 : 10280-, 2018

35 Wang, B., "Highly efficient synthesis of capsaicin analogues by condensation of vanillylamine and acyl chlorides in a biphase H2O/CHCl3system" 65 : 5409-5412, 2009

36 Appendino, G., "Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists" 139 : 1417-1424, 2003

37 Figueroa-Espinoza, M. C., "From phenolics to phenolipids : optimizing antioxidants in lipid dispersions" 25 : 131-134, 2013

38 Perva-Uzunalic, A., "Extraction of chilli pepper (var. Byedige) with supercritical CO2: Effect of pressure and temperature on capsaicinoid and colour extraction efficiency" 87 : 51-58, 2004

39 Singh, C. U., "Esters of capsaicinoids as dietary supplements"

40 Singh, C. U., "Esters of capsaicin for treating pain"

41 Pérez-Gálvez, A., "Esterification of xanthophylls and its effect on chemical behavior and bioavailability of carotenoids in the human" 25 : 631-640, 2005

42 Guyot, B., "Esterification of phenolic acids from green coffee with an immobilized lipase from Candida antarctica in solvent-free medium" 19 : 529-532, 1997

43 Hee-Jeong Cha, "Esterification of Secondary Alcohols and Multi-hydroxyl Compounds by Candida antarctica Lipase B and Subtilisin" 한국생물공학회 24 (24): 41-47, 2019

44 Seo, E. J., "Enzyme/whole-cell biotransformation of plant oils, yeast derived oils, and microalgae fatty acid methyl esters into n-nonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid" 251 : 288-294, 2018

45 Sheldon, R. A., "Enzyme immobilisation in biocatalysis: why, what and how" 42 : 6223-6235, 2013

46 Lee, D., "Enzyme cascade reactions for the biosynthesis of long chain aliphatic amines from renewable fatty acids" 361 : 1359-1367, 2019

47 Castillo, E., "Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels" 356 : 424-430, 2007

48 Pihko, A. J., "Enantioselective synthesis of a hindered furyl substituted allyl alcohol intermediate : a case study in asymmetric synthesis" 15 : 1637-1643, 2004

49 Andelt, W. F., "Effectiveness of capsaicin and bitrex repellents for deterring browsing by captive mule deer" 58 : 330-334, 1994

50 Fitzgerald, C. S., "Effectiveness of Capsaicin as a repellent to birdseed consumption by gray squirrels" 1995

51 Rocha-Uribe, J. A., "Cost estimation for CO2 supercritical extraction systems and manufacturing cost for habanero chili" 93 : 38-41, 2014

52 Koleva-Gudeva, L., "Content of capsaicin extracted from hot pepper (Capsicum annuum ssp. microcarpum L.) and its use as an ecopesticide" 67 : 671-675, 2013

53 Fernández-García, E., "Changes in composition of the lipid matrix produce a differential incorporation of carotenoids in micelles. Interaction effect of cholesterol and oil" 8 : 379-384, 2007

54 Minguez-Mosquera, M. I., "Changes in carotenoid esterification during the fruit ripening of Capsicum annuum Cv" 42 : 640-644, 1994

55 Mercadante, A. Z., "Carotenoid esters in foods-A review and practical directions on analysis and occurrence" 99 : 830-850, 2017

56 Urban, L., "Capsazepine, a novel capsaicin antagonist, selectively antagonises the effects of capsaicin in the mouse spinal cord in vitro" 134 : 9-11, 1991

57 Bevan, S., "Capsazepine : a competitive antagonist of the sensory neurone excitant capsaicin" 107 : 544-552, 1992

58 Maliszewska, J., "Capsaicin as an organophosphate synergist against colorado potato beetle(Leptinotarsa decemlineata Say)" 52 : 28-34, 2012

59 Domínguez De María, P., "Biotechnological applications of Candida antarctica lipase A : State-of-the-art" 37 : 36-46, 2005

60 Wohlgemuth, R., "Biocatalysis — key to sustainable industrial chemistry" 21 : 713-724, 2010

61 Molina-Torres, J., "Antimicrobial properties of alkamides present in flavouring plants traditionally used in Mesoamerica : affinin and capsaicin" 64 : 241-248, 1999

62 Wrigglesworth, R., "Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 4. Potent, orally active analgesics" 39 : 4942-4951, 1996

63 Walpole, C. S. J., "Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 1. The aromatic “Aregion.”" 36 : 2362-2372, 1993

64 Seo, J. H., "Adding value to plant oils and fatty acids: biological transformation of fatty acids into ω-hydroxycarboxylic, α,ω-dicarboxylic, and ω-aminocarboxylic acids" 216 : 158-166, 2015