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Synlett 2008(18): 2869-2873  
DOI: 10.1055/s-0028-1083521
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Chemoenzymatic Synthesis of Phenylacetylrinvanil: An Ultrapotent Capsaicinoid

Edmundo Castillo*a, Ignacio Regla*b, Patricia Demareb, Axel Luviano-Jardónb, Agustín López-Munguíaa
a Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Apdo. Postal 510-3, Cuernavaca, Morelos 62271, Mexico
Fax: +52(73)172388; e-Mail: edmundo@ibt.unam.mx;
b Facultad de Estudios Superiores-Zaragoza, UNAM, Batalla del 5 de Mayo esq. Fuerte de Loreto, Ejercito de Oriente, 09230 México, D.F., México
e-Mail: regla@unam.mx;
Further Information

Publication History

Received 27 April 2008
Publication Date:
01 October 2008 (online)

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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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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.