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DOI: 10.1055/s-0028-1083521
Efficient Chemoenzymatic Synthesis of Phenylacetylrinvanil: An Ultrapotent Capsaicinoid
Publication History
Publication Date:
01 October 2008 (online)
Abstract
The straightforward synthesis of phenylacetylrinvanyl (PhAR), an ultrapotent capsaicinoid is described. The process starts with the quantitative synthesis of methyl ricinoleate (MeRic) by castor oil methanolysis. Afterwards, two alternative routes are possible: a) chemoselective vanillylamine aminolysis of MeRic catalyzed by Candida antarctica lipase-B (CaLB) to yield rinvanil, which after reaction with phenylacetic acid and DCC-DMAP followed by a regioselectively pyrrolidine deacylation results in PhAR with a 51% global yield, b) methyl 12-phenylacetylricinoleate synthesis by reaction of MeRic with phenylacetic acid and DCC-DMAP, followed by a chemoselective vanillylamine aminolysis catalyzed by CaLB to obtain PhAR with a 70% global yield.
Key words
chemoselective synthesis - solvent effects - enzymes - Candida antarctica B - ultrapotent capsaicinoid
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Caterina MJ.Schumacher MA.Tominaga M.Rosen TA.Levine JD.Julius D. Nature (London) 1997, 389: 816 - 2a
Walker KM.Urban L.Medhurst SJ.Patel S.Panesar M.Fox AJ.McIntyre P. J. Pharmacol. Exper. Ther. 2003, 304: 56Reference Ris Wihthout Link - 2b
Voets T.Droogmans G.Wissenbach U.Janssens A.Flockerzi V.Nilius B. Nature (London) 2004, 430: 748Reference Ris Wihthout Link - 3
Yiangou Y.Facer P.Dyer NHC.Chan CLH.Knowles C.Williams NS.Anand P. Lancet 2001, 357: 1338 - 4
Winter J.Bevan S.Campbell EA. Br. J. Anaesth. 1995, 75: 157 - 5a
Appendino G.De Petrocellis L.Trevisani M.Minassi A.Daddario N.Moriello AS.Gazzieri D.Ligresti A.Campi B.Fontana G.Pinna C.Geppetti P.Di Marzo V. J. Pharmacol. Exp. Ther. 2005, 312: 561Reference Ris Wihthout Link - 5b
Appendino G.Cascio MG.Bacchiega S.Moriello AS.Minassi A.Thomas A.Ross R.Pertwee R.De Petrocellis L.Di Marzo V. FEBS Lett. 2006, 580: 568Reference Ris Wihthout Link - 6
Iida T.Moriyama T.Kobata K.Morita A.Murayama N.Hashizume S.Fushiki T.Yazawa S.Watanabe T.Tominaga M. Neuropharmacology 2003, 44: 958 - 7
Brand L.Berman E.Schwen R.Loomans M.Janusz J.Bohne R.Maddin C.Gardne J.Lahann T.Farmer R.Jones L.Chiabrando C.Fanneli R. Drug Exp. Clin. Res. 1987, 13: 259 - 8
Voets T.Droogmans G.Wissenbach U.Janssens A.Flockerzi V.Nilius B. Nature (London) 2004, 430: 748 - 9
Andersson KE. Urology 2004, 63: 32 - 10
Morazzoni P,Riva A,Fontana G,Appendino G, andDi Marzo V. inventors; WO 2006010445.Reference Ris Wihthout Link - 11
Dorado MP.Ballesteros E.Mittelbach M.López FJ. Energy Fuels 2004, 18: 1457 - 12
Appendino G.Minassi AN. J. Med. Chem. 2002, 45: 3739 - 13
Walpole CS.Wrigglesworth R.Bevan S.Campbell EA.Dray A.James IF.Masdin KJ.Perkins MN.Winter J. J. Med. Chem. 1993, 36: 2381 - 14
Reyes-Duarte D.Castillo E.Martínez R.López-Munguía A. Biotechnol. Lett. 2002, 24: 2057 - 15a
Castillo E.López-González I.de Regil-Hernández R.Reyes-Duarte D.Sánchez-Herrera D.López-Munguía A.Darszon A. Biochem. Biophys. Res. Commun. 2007, 356: 424Reference Ris Wihthout Link - 15b
Torres-Gavilán A.Escalante J.Regla I.López-Munguía A.Castillo E. Tetrahedron: Asymmetry 2007, 2621Reference Ris Wihthout Link - 16
Borsotti G.Guglielmetti G.Speras S.Battistel E. Tetrahedron 2001, 57: 10219
References and Notes
¹H and ¹³C NMR spectroscopy was carried out on a JEOL Eclipse instrument at 300 and 400 MHz (¹H NMR operating frequency), with TMS as an internal standard and CDCl3 as solvent. The IR spectra were carried out on a Bruker spectrophotometer Tensor 27. The [a]D ²0 values were determined on a 341 Perkin Elmer polarimeter, at 1 dm cell length. HRMS was determined on a JEOL JMS-SX102A instrument. Silica gel chromatography: 70-230 mesh. Multiplicity keys: s = singlet, d = doublet, t = triplet, c = quartet, q = quintet, m = multiplet, br = broad, dd = doublet of doublets.