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Synthesis 2016; 48(13): 2085-2092
DOI: 10.1055/s-0035-1561580
DOI: 10.1055/s-0035-1561580
paper
Total Synthesis of δ-Sanshool and Analogues Thereof
Further Information
Publication History
Received: 14 January 2016
Accepted after revision: 16 February 2016
Publication Date:
16 March 2016 (online)
Abstract
Two simple synthetic approaches were developed for the total synthesis of δ-sanshool, an isobutylamide characterized by a C14 pentaunsaturated chain with all trans double bonds and proposed as a promising lead for the treatment of type-1 diabetes due to its dual activity on cannabinoid (CB) receptors. The syntheses are based on a suitably protected core fragment derived from 1,4-butanediol. These strategies also enable the preparation of small libraries of chemical analogues modified at either the polyunsaturated alkyl chain or the amidic head for use in SAR studies.
Key words
sanshools - alkamides - trienes - Horner–Wadsworth–Emmons reaction - cannabinoid receptorsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561580.
- Supporting Information
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References
- 1 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
- 2 Rios MY, Olivo HF. Natural and Synthetic Alkamides: Applications in Pain Therapy. In Studies in Natural Products Chemistry. Atta-ur-Rahman, Elsevier; Oxford: 2014: 79-121
- 3 Greger H. Phytochem. Rev. 2015; in press; DOI: 10.1007/s11101-015-9418-0
- 4 Kashiwada Y, Ito C, Katagiri H, Mase I, Komatsu K, Namba T, Ikeshiro Y. Phytochemistry 1997; 44: 1125
- 5 Etsuko S, Yasujiro M, Yusaku I, Akihito M, Tatsuo W, Kikue K. Biosci. Biotechnol. Biochem. 2005; 69: 1951
- 6 Warnock WM. US 20120263808, 2012
- 7 Dossou KS. S, Devkota KP, Morton C, Egan JM, Lu G, Beutler JA, Moaddel R. J. Nat. Prod. 2013; 76: 2060
- 8 Kim W, Doyle ME, Liu Z, Lao Q, Shin Y.-K, Carlson OD, Kim HS, Thomas S, Napora JK, Lee EK, Moaddel R, Maudsley YW. S, Martin B, Kulkarni RN, Egan JM. Diabetes 2011; 60: 1198
- 9 Crombie L, Fisher D. Tetrahedron Lett. 1985; 26: 2481
- 10 Yang X. J. Agric. Food Chem. 2008; 56: 1689
- 11 Aoki K, Igarashi Y, Nishimura H, Morishita I, Usui K. Tetrahedron Lett. 2012; 53: 6000
- 12 Mann S, Carillon S, Breyne O, Marquet A. Chem. Eur. J. 2002; 8: 439
- 13 Bennacer B, Trubuil S, Rivalle C, Grierson DS. Eur. J. Org. Chem. 2003; 23: 4561
- 14 Burke LT, Dixon DJ, Ley SV, Rodriguez F. Org. Biomol. Chem. 2005; 3: 274
- 15 Castilho MS, Pavão F, Oliva G, Ladame S, Willson M, Périé J. Biochemistry 2003; 42: 7143