Synthesis of Bungeanool, Isobungeanool, Dihydrobungeanool, Tetrahydrobungeanool, Hazaleamide, Lanyuamide III, and Analogues

Abstract

The bungeanools are a family of alkamide natural products isolated from the pericarps of Zanthoxylum bungeanum (Sichuan pepper), and they are structurally related to the sanshools. While the sanshools, especially hydroxy-α-sanshool, have been studied in a variety of contexts, research regarding the bungeanools has been much more limited. To facilitate their study, we have developed stereoselective syntheses of all four members of this family of compounds by using flexible routes that are also amenable to the synthesis of analogues. The key transformation in the syntheses was the stereoselective triphenylphosphine/phenol-catalyzed isomerization of an alkynoate to the corresponding conjugated E,E-dienoate.

Key words

alkamides - bungeanool - isobungeanool - dihydrobungeanol - tetrahydrobungeanol - hazaleamide - lanyuamide III - natural product synthesis

Publikationsverlauf

Eingereicht: 10. August 2021

Angenommen nach Revision: 24. September 2021

Accepted Manuscript online:
24. September 2021

Artikel online veröffentlicht:
25. Oktober 2021

• References

• 1 For a comprehensive review of the polyunsaturated fatty acid amides from the Zanthoxylum genus, see: Chruma JJ, Cullen DJ, Bowman L, Toy PH. Nat. Prod. Rep. 2018; 35: 54
• 2 For a comprehensive review of alkamide natural products, see: Greger H. Phytochem. Rev. 2016; 15: 729
• 3 Xiong Q, Shi D, Yamamoto H, Mizuno M. Phytochemistry 1997; 46: 1123
• 4 Chen J, Zhang T, Zhang Q, Liu Y, Li L, Si J, Zou Z, Hua H. J. Agric. Food Chem. 2018; 66: 3408
• 5 Chen I.-S, Chen T.-L, Lin W.-Y, Tsai I.-L, Chen Y.-C. Phytochemistry 1999; 52: 357
• 6 Zhao Z.-F, Zhu R.-X, Zhong K, He Q, Luo A.-M, Gao H. J. Food Sci. 2013; 78: C1516
• 7 Mizutani K, Fukunaga Y, Tanaka O, Takasugi N, Saruwatari Y.-I, Fuwa T, Yamauchi T, Wang J, Jia M.-R, Li F.-Y, Ling Y.-K. Chem. Pharm. Bull. 1988; 36: 2362
• 8 Yang X. J. Agric. Food Chem. 2008; 56: 1689
• 9 Yasuda I, Takeya K, Itokawa H. Phytochemistry 1982; 21: 1295
• 10 Sugai E, Morimitsu Y, Iwasaki Y, Morita A, Watanabe T, Kubota K. Biosci., Biotechnol., Biochem. 2005; 69: 1951
• 11 Bader M, Stark TD, Dawid C, Lösch S, Hofmann T. J. Agric. Food Chem. 2014; 62: 2479
• 12 Koo JY, Jang Y, Cho H, Lee C.-H, Jang KH, Chang YH, Shin J, Oh U. Eur. J. Neurosci. 2007; 26: 1139
• 13 Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D. Nat. Neurosci. 2008; 11: 772
• 14 Riera CE, Menozzi-Smarrito C, Affolter M, Michlig S, Munari C, Robert F, Vogel H, Simon SA, le Coutre J. Br. J. Pharmacol. 2009; 157: 1398
• 15 Tsunozaki M, Lennertz RC, Vilceanu D, Katta S, Stucky CL, Bautista DM. J. Physiol. 2013; 591: 3325
• 16 Dossou KS. S, Devkota KP, Morton C, Egan JM, Lu G, Beutler JA, Moaddel R. J. Nat. Prod. 2013; 76: 2060
• 17 Wang Y, Li C.-H, Luo B, Sun YN, Kim YH, Wei A.-Z, Gao J.-M. Molecules 2016; 21: 1416
• 18 Wang Y, Liao Z.-B, Cao R, Li H, Wei A.-Z, Gao JM. Nat. Prod. Commun. 2017; 12: 1121
• 19 Galopin CC, Furrer SM, Goeke A. Pungent and Tingling Compounds in Asian Cuisine . In Challenges in Taste Chemistry and Biology, ACS Symposium Series 876 . Hofmann T, Ho CT, Pickenhagen W. American Chemical Society; Washington DC: 2004: 139-152
• 20 For a more recent report regarding the pungency of 1 and 5, see: Zhang L.-L, Zhao L, Wang H.-Y, Shi B.-L, Liu L.-Y, Chen Z.-X. J. Sci. Food Agric. 2019; 99: 1475
• 21 Sonnet PE. J. Org. Chem. 1969; 34: 1147
• 22 Shibuya H, Takeda Y, Zhang R.-S, Tong R.-X, Kitagawa I. Chem. Pharm. Bull. 1992; 40: 2325
• 23 Wu B, Li K, Toy PH. Synlett 2012; 23: 2564
• 24 For a recent related synthesis of 5 that was not covered in reference 1, see: Nakamura A, Mimaki K, Tanigami K.-i, Maegawa T. Front. Chem. 2020; 137
• 25 Xia X, Toy PH. Synlett 2014; 25: 2787
• 26 Trost BM, Kazmaier U. J. Am. Chem. Soc. 1992; 114: 7933
• 27 Guo C, Lu X. J. Chem. Soc., Chem. Commun. 1993; 394
• 28 Kwong CK.-W, Fu MY, Lam CS.-L, Toy PH. Synthesis 2008; 2307
• 29 For the use of this reaction in the synthesis of some structurally related alkylamides, see: Strunz GM, Finlay HJ. Can. J. Chem. 1996; 74: 419
• 30 Mugnaini C, Corelli F. Synthesis 2016; 48: 2085
• 31 Sawyer CM, Carstens MI, Simmons CT, Slack J, McCluskey TS, Furrer S, Carstens E. J. Neurophysiol. 2009; 101: 1742
• 32 Albin KC, Simons CT. PLoS ONE 2010; e9520
• 33 Klein A, Sawyer CM, Zanotto KL, Ivanov MA, Cheung S, Carstens MI, Furrer S, Simons CT, Slack JP, Carstens E. J. Neurophysiol. 2011; 105: 1701
• 34 Klein A, Carstens MI, Carstens E. J. Neurophysiol. 2011; 106: 1078
• 35 Tulleuda A, Cokic B, Callejo G, Saiani B, Serra J, Gasull X. Mol. Pain 2011; 7: 30
• 36 Callejo G, Giblin JP, Gasull X. PLoS ONE 2013; e64471
• 37 Dallazen JL, Maria-Ferreira D, da Luz BB, Nascimento AM, Cipriani TR, de Souza LM, Glugoski LP, Silva BJ. G, Geppetti P, Fernanda de Paula Werner M. Fitoterapia 2019; 131: 225