TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 14 (2003) 543–548 Pergamon The absolute configuration of cuauhtemone and related compounds J. Martı ´n Torres-Valencia, a, * Dora L. Quintero-Mogica, a Guadalupe I. Leo ´n, a Oscar R. Sua ´rez-Castillo, a J. Roberto Villago ´ mez-Ibarra, a Emma Maldonado, b Carlos M. Cerda-Garcı ´a-Rojas c and Pedro Joseph-Nathan c a Centro de Investigaciones Quı ´micas, Universidad Auto ´noma del Estado de Hidalgo, Apartado 1 -622, Pachuca, Hidalgo 42001, Mexico b Instituto de Quı ´mica, Universidad Nacional Auto ´noma de Me ´xico, Circuito Exterior, Cd. Universitaria, Coyoaca ´n, Me ´xico, D.F. 04510, Mexico c Departamento de Quı ´mica, Centro de Investigacio ´n y de Estudios Avanzados del Instituto Polite ´cnico Nacional, Apartado 14 -740, Me ´xico, D.F. 07000, Mexico Received 10 October 2002; accepted 3 January 2003 Abstract—The absolute configuration of cuauhtemone, a eudesmane-type sesquiterpene isolated from Pluchea species (Aster- aceae), has been revised from 1 to 2 by chemical correlation with (R )-(+)-2-methyl-1,2-butanediol 3 through the naturally occurring 2,3-epoxy-2-methylbutanoate derivative 4. The relative stereochemistry of 4 was confirmed by X-ray diffraction analysis. The obtained data are also useful for reconsideration of the absolute configurations of a relevant group of natural products, which were elucidated according to the stereochemistry of cuauhtemone. © 2003 Elsevier Science Ltd. All rights reserved. 1. Introduction Cuauhtemone is a bicyclic eudesmane-type sesquiter- pene isolated from the aerial parts of Pluchea species 1–3 to which growth inhibition activity of corn and bean seeds has been attributed. 1,4 Since the flexibility of the enone group precluded the application of various rules for determining its chirality, the absolute configuration of the molecule was proposed using CD measurements in the absence and presence of a europium NMR shift reagent. 1 By doing so, it seems that the authors neglected the severe steric effects to which the NMR shift reagents are exposed, 5,6 and therefore assumed that the secondary and tertiary hydroxyl groups present in the 1,2-diol moiety of the natural product should behave as the model secondary diol compounds 7 used to develop the methodology for absolute configura- tion determination. Since then, the stereochemistry of various eudesmane derivatives has been described based on the erroneous absolute configuration of cuauhtemone, 1–4,8–25 whose structure and relative stereo- chemistry was secured by X-ray diffraction analysis. 4 Herein, the absolute configuration of cuauhtemone is revised from 1 to 2 by means of chemical correlation with (R )-(+)-2-methyl-1,2-butanediol 3 26,27 through the naturally occurring 2,3-epoxy-2-methylbutanoate derivative 4. The stereochemical relationship between the ester residue and the sesquiterpenic moiety in com- pound 4 is confirmed herein by X-ray diffraction analy- sis. Compound 4 is a bioactive natural product 23 isolated from Pluchea foetida (L.) D.C., 2 P. odorata Cass., 8 P. symphytifolia (Miller) Gills, 13 Laggera alata (D. Don) Schultz-Bip. ex Oliver, 19 and Epaltes mexi - cana Less. 20,23 2. Results and discussion A methodology to determine the absolute configuration of 2,3-epoxy-2-methylbutanoate ester residues (epoxyangelate or epoxytiglate moieties) in natural products, based on reduction of the ester functionality to yield a 2-methyl-1,2-butanediol, esterification of the obtained primary alcohol with either the (R )-(+)- or (S )-(-)-Mosher acid to afford the corresponding Mosher ester, and 1 H NMR spectral comparison of the final product with those of the Mosher esters prepared * Corresponding author. Fax: (52-771) 717-2000 internal number 6502; e-mail: jmartin@uaeh.reduaeh.mx 0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0957-4166(03)00042-9