Synthesis 2016; 48(13): 2085-2092
DOI: 10.1055/s-0035-1561580
paper
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of δ-Sanshool and Analogues Thereof

Claudia Mugnaini*
Dipartimento di Biotecnologie Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 53100 Siena, Italy   Email: claudia.mugnaini@unisi.it
,
Federico Corelli
Dipartimento di Biotecnologie Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 53100 Siena, Italy   Email: claudia.mugnaini@unisi.it
› Author Affiliations
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.

Supporting Information

 
  • 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