Tetrahedron Letters,Vol.30,No.21,pp 2851-2854,1989 0040-4039/89 $3.00 •t .OO Printed in Great Britain Perqamon Press plc AQUAT0UDE.A NEW TYPE OF HUMULANE-RELATED SESQUITERPENE LACTONE A. San Feliciano*, M. Medarde, J.M. Miguel del Corral, A. Aramburu, M. Gordalira and A.F. Barreroa Depto de Quimica O@nica y Fafmac&&.a Facultad de Farmacia. 37007-Salamanca-Spain. a)Depto de Quimica OrgMca. Facultad de Ciencias. Granada. Spain Summary: A new sesquiterpene lactone called aquatolide was isolated from the hexane extract of Asteriscus aquaticus. Its constitution and stereochemistry were deduced from spectroscopic data, mainly homonuclear and heteronuclear two-dimensional NMR correlations. From the neutral part of a methanol deffated hexane extract of Asteriscus aquaticus L. (family, Compositae; Tribe, Inuleae), by repeated chromatography and crystallization, a small amount of a new substance zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1 was isolatedt. Its origin and the preliminar analysis of its spectroscopic properties, readily suggested the structure of a sesquiterpene lactone for the compound. Its MS displayed the M+ at m/z= 2462 in the El mode and showed peaks at m/z = 281 (M+ + 35) and m/z = 264 (M+ + 18) in the Cl mode (NHa). These data, together with tsC NMR data obtained from its BB decoupled and DEPT spectra (Table I), established a molecular formula of Ct5HtaOs for aquatolide. In its IR spectrum prominents bands of saturated y-lactone (1770 cm-t) and a,p- unsaturated ketone (1680 cm-t) accounted for all the oxygenated functions in the molecule. Conjugation of the carbonyl group was confirmed by an absorption maximum at 240 nm in the UV spectrum and the presence of only one double bond, as was deduced from the signals at 130.9 and 135.0 ppm in the 1% NMR spectrum, permitted us to deduce the existence of four rings in the molecule. The 1 H-NMR spectrum of aquatolide ( fig la, Table I) showed two methyl singlets at 1.04 and 1.18 ppm, as well as another three protons signal (1.86 ppm), assigned to a methyl attached to an oiefinic carbon. Furthermore, signals of a deshielded olefinic proton (5.84 ppm) and of a proton geminal to the lactone oxygen (4.48 ppm), which formed an AMX system with another two protons absorbing at 3.26 and 2.64 ppm were also observed. A singlet of one proton at 2.92 ppm and some overlapping multiplets in the range between 1.8 and 2.6 ppm, corresponding to four protons, completed the spectrum. In agreement with these data, apart from the signals of two carbonyls, two olefinic carbons and one oxygenated methine, the 1% NMR spectrum of aquatolide (fig. lc) showed signals for three methyls, two methylenes, three methines and two sp9 quaternary carbons. With these data, also taking into consideration the large deshielding of the methines (54.3, 54.4 and 62.5 ppm), which were similar to those of photoisabelins, as well as the structure of Asteriscunolides A - D and Asteriscanolide, described by us previously as metabolites of A. aquaticus4,5, we were able to propose the structure 1 for aquatolide. 2851