Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Studies Towards the Synthesis of Salvinorin A

Anthony R. Lingham A , Helmut M. Hügel A and Trevor J. Rook A B
+ Author Affiliations
- Author Affiliations

A RMIT University, School of Applied Sciences, Melbourne VIC 3001, Australia.

B Corresponding author. Email: trevor.rook@rmit.edu.au

Australian Journal of Chemistry 59(5) 340-348 https://doi.org/10.1071/CH05338
Submitted: 20 December 2005  Accepted: 25 May 2006   Published: 13 June 2006

Abstract

Salvinorin A 1, a psychoactive neoclerodane diterpenoid from the Mexican sage S. divinorum, has gained interest as a selective κ-opioid receptor agonist. Non-racemic 3-furylamines 9a and 9b have been prepared from (+)-pseudoephedrine and (–)-ephedrine for application in the stereoselective synthesis of the ketone ring of 1. Diels–Alder reaction of 9b with methyl acrylate in aqueous media, followed by selective ether bridge cleavage, has allowed access to the cyclohexenone 17 with preservation of stereochemistry at C2. A model route to the lactone ring has also been achieved through a one-pot deconjugation/esterification procedure of 2-bromocrotonyl chloride 20 to the furyl alcohol 19 followed by Reformatski-mediated ring closure.


Acknowledgments

Financial support from the School of Applied Science, RMIT University, is acknowledged. We thank Dr Julie Niere, Dr Peter McKay, and Dr Gary Amiet for their advice on synthetic problems and NMR interpretation, and Britta Drevermann for assistance with manuscript revisions. Technical assistance from Paul Morrison, Daniel Diaz, Daniel Beck (ANU), Dr Jo Cosgriff (CSIRO), and Dr Roger Mulder (CSIRO) is gratefully acknowledged. We also thank Dr Jonathan White (Melbourne University) for X-ray crystal structure data, Sally Duck (Monash University) for high-resolution mass spectrometry analysis, and Dr John Zdysiewicz for assistance with organic nomenclature. We also thank Dr Jim Pearson (VFSC) for support throughout this project.


References


[1]   A. Ortega, J. F. Blount, P. D. Manchland, J. Chem. Soc., Perkin Trans. 1 1982,  2505.
        | CrossRef |   

[2]   L. J. Valdés, W. M. Butler, G. M. Hatfield, A. G. Paul, M. Koreeda, J. Org. Chem. 1984, 49,  4716.
        | CrossRef |   

[3]   (a) L. J. Valdés, J. Psych. Drugs 1994, 26,  277.
         
       (b) D. J. Siebert, J. Ethnopharmacol. 1994, 43,  53.
        | CrossRef |   

[4]   M. Koreeda, L. Brown, L. J. Valdés, Chem. Lett. (Jpn.) 1990,  2015.
        | CrossRef |   

[5]   B. L. Roth, K. Baner, R. Westkaemper, D. Siebert, K. C. Rice, S. Steinberg, P. Ernsberger, R. B. Rothman, Proc. Natl. Acad. Sci. USA 2002, 99,  11934.
        | CrossRef |   

[6]   F. Yan, B. L. Roth, Life Sci. 2004, 75,  2615.
        | CrossRef |   

[7]   C. Chavkin, S. Sud, W. Jin, J. Stewart, J. K. Zjawiony, D. J. Siebert, B. A. Toth, S. J. Hufeisen, B. L. Roth, J. Pharmacol. Exp. Ther. 2003, 308,  1197.
        | CrossRef |   

[8]   D. J. Siebert, Ann. Bot. (Lond.) 2004, 93,  763.
        | CrossRef |   

[9]   L. J. Valdés, H.-M. Chang, D. C. Visger, M. Koreeda, Org. Lett. 2001, 3,  3935.
        | CrossRef |   

[10]   T. A. Munro, M. A. Rizzacasa, J. Nat. Prod. 2003, 66,  703.
        | CrossRef |   

[11]   D. Y. W. Lee, Z. Ma, L.-Y. Liu-Chen, Y. Wang, Y. Chen, W. A. Carlezon, B. Cohen, Bioorg. Med. Chem. Lett. 2005, 13,  5635.
        | CrossRef |   

[12]   W. W. Harding, K. Tidgewell, M. Schmidt, K. Shah, C. M. Dersch, J. Snyder, D. Parrish, J. R. Deschamps, R. B. Rothman, T. E. Prisinzano, Org. Lett. 2005, 7,  3017.
        | CrossRef |   

[13]   A. K. Bigham, T. A. Munro, M. A. Rizzacasa, R. M. Robins-Browne, J. Nat. Prod. 2003, 66,  1242.
        | CrossRef |   

[14]   D. Y. W. Lee, V. V. R. Karnati, M. He, L.-Y. Liu-Chen, L. Kondaveti, Z. Ma, Y. Wang, Y. Chen, C. Beguin, W. A. Carlezon, B. Cohen, Bioorg. Med. Chem. Lett. 2005, 15,  3744.
        | CrossRef |   

[15]   W. W. Harding, K. Tidgewell, N. Byrd, H. Cobb, C. M. Dersch, E. R. Butelman, R. B. Rothman, T. E. Prisinzano, J. Med. Chem. 2005, 48,  4765.
        | CrossRef |   

[16]   D. Y. W. Lee, M. He, L. Kondaveti, L.-Y. Liu-Chen, Z. Ma, Y. Wang, Y. Chen, J.-G. Li, C. Beguin, W. A. Carlezon, Bioorg. Med. Chem. Lett. 2005, 15,  4169.
        | CrossRef |   

[17]   T. A. Munro, G. W. Goetchius, B. L. Roth, T. A. Vortherms, M. A. Rizzacasa, J. Org. Chem. 2005, 70,  10057.
        | CrossRef |   

[18]   C. Giroud, F. Felber, M. Augsburger, B. Horisberger, L. Rivier, P. Mangin, Forensic Sci. Int. 2000, 112,  143.
        | CrossRef |   

[19]   K. Tidgewell, W. W. Harding, M. Schmidt, K. G. Holden, D. J. Murry, T. E. Prisinzano, Bioorg. Med. Chem. Lett. 2004, 14,  5099.
        | CrossRef |   

[20]   G. Wurzel, H. Becker, Th. Eicher, K. Tiefensee, Planta Med. 1990, 56,  444.
         

[21]   (a) H. Wagner, R. Seitz, H. Lotter, J. Org. Chem. 1978, 43,  3339.
        | CrossRef |   
         (b) R. D. Enriz, H. A. Baldoni, M. A. Zamora, E. A. Jauregui, M. E. Sosa, C. E. Tonn, J. M. Luco, M. Gordaliza, J. Agric. Food Chem. 2000, 48,  1384.
        | CrossRef |   

[22]   (a) P. Vogel, J. Cossy, J. Plumet, O. Arjona, Tetrahedron 1999, 55,  13521.
        | CrossRef |   
         (b) P. Vogel, D. Fattori, F. Gasparini, C. Le Drian, Synlett 1990, 4,  173.
        | CrossRef |   
         (c) D. Josien-Lefebvre, C. Le Drian, Helv. Chim. Acta 2001, 84,  890.
        | CrossRef |   
         (d) D. Josien-Lefebvre, C. Le Drian, Helv. Chim. Acta 2003, 86,  661.
        | CrossRef |   

[23]   G. Stork, A. Brizzolara, H. Landesman, J. Szmuszkovicz, R. Terrell, J. Am. Chem. Soc. 1963, 85,  207.
        | CrossRef |   

[24]   A. R. Lingham, T. J. Rook, H. M. Hügel, Aust. J. Chem. 2002, 55,  795.
        | CrossRef |   

[25]   A. R. Lingham, T. J. Rook, H. M. Hügel, Aust. J. Chem. 2006, 59,  336.
        | CrossRef |   

[26]   R. H. Schlessinger, T. R. R. Pettus, J. P. Springer, K. Hoogsteen, J. Org. Chem. 1994, 59,  3246.
        | CrossRef |   

[27]   R. H. Schlessinger, C. P. Bergstrom, J. Org. Chem. 1995, 60,  16.
        | CrossRef |   

[28]   R. O. Hutchins, W.-Y. Su, R. Sivakumar, F. Cistone, Y. P. Stercho, J. Org. Chem. 1983, 48,  3412.
        | CrossRef |   

[29]   C. Le Drian, J.-P. Vionnet, P. Vogel, Helv. Chim. Acta 1990, 73,  161.
        | CrossRef |   

[30]   T. Takahashi, T. Namiki, Y. Takeuchi, T. Koizumi, Chem. Pharm. Bull. (Tokyo) 1988, 36,  3213.
         

[31]   (a) Q. Zhu, L. Qiao, Y. Wu, Y.-L. Wu, J. Org. Chem. 2001, 66,  2692.
        | CrossRef |   
         (b) T. K. M. Shing, Q. Jiang, J. Org. Chem. 2000, 65,  7059.
        | CrossRef |   

[32]   Y. Iwakura, F. Toda, R. Iwata, Y. Torii, Bull. Chem. Soc. Jpn. 1969, 42,  841.
         

[33]   P. Pfeiffer, Chem. Ber. 1910, 43,  3039.
         

[34]   J. Klein, S. Zitrin, J. Org. Chem. 1970, 35,  666.
        | CrossRef |   

[35]   G. Cardillo, A. De Simone, A. Mingardi, C. Tomasini, Synlett 1995, 11,  1131.
        | CrossRef |   



Rent Article (via Deepdyve) Export Citation Cited By (12)

View Altmetrics