Phytochemistry, Vol. 32, No. 2, pp.401405, 1993 Printed in Great Britain. 003 l-9422/93 $6.00 + 0.00 0 1993 Pergmon Press Ltd zyxwvutsrqpo A* LABDANES FROM zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCB HALIMIUM VERTICILLATUM J. G. URONES, I. S. MARCO& R. F. MORO, J. M. L. RODILLA* and A. GERALDES MENDONCA* Departamento de Quimica Organica Universidad de Salamanca, Facultad de Quhnicas, Plaza de 10s Caidos l-5.37008 Sakunanca, Spain; *Departamento de Quimica, Universidade da Beira Interior, 6200 Covilht?, Portugal zyxwvutsrqponmlkjihgfedcb (Receioed in reuised form 1 June 1992) Key Word Index-Halimium oerticillatum; Cistaceae; diterpene; labdane; nor-labdane. Abstract-Three new acids in the form of methyl esters and the acetyl derivative of an alcohol have been isolated from Halimium verticillatum. Their structures have been established by spectroscopic methods and/or chemical correlations as those of methyl 15hydroxy-7-oxo-8-labden-17-oate, methyl 7a,l5-dihydroxy-glabden-17-oate, methyl 7/3,15- dihydroxy-8-labden-17-oate and 17-nor-15acetoxy-7-oxo-8-labdene. INTRODUCTION Halimium verticillatum contains diterpenic acids with a labdane skeleton having an a&unsaturated carboxyl group at C-17 [l]. In order to make some trans- formations of the major product of the n-hexane extract, we re-examined it. In this paper, we report on the isolation and characterization of four new As labdanes (1, 3-5) from H. uerticillatum. We also revise the stereochem- istry at C-6 of the hydroxy ester (2) earlier reported [ 1,2]. BESULTS AND DISCUSSION Compounds l-4 were isolated as methyl esters from the acid part of the hexane extract of H. verticillatum Compound 5 was isolated from the neutral part. Compound 1 could be only separated from the major product 6, by column chromatography of the acetyl derivatives. Its IR spectrum shows bands of an a# - unsaturated ketone (1670 and 1605 cm- ‘), an ester (1730cm-‘) and an acetate group (1740cm-‘). The ‘H NMR spectrum shows signals of the following group- ings: CH,-CH,OAc (64.05, 2H, t, J=6.8 Hz), CO,Me (63.76, 3H, s), three Me-C (61.13, 0.90 and 0.83, 3H, s each) and one CH-Me (60.83, 3H, d, 5=6.7 Hz). The 1 3C NMR spectrum contains peaks corresponding to 23 carbon atoms: six methyl groups, eight methylenes; two methynes and seven tetrasubstituted carbons. of these, one wan a carbonyl (6196.2), two carboxyl (6171.0 and 172.0) and the other two olefinic (6 132.5 and 167.9). Compound 1 was obtained by oxidation of 6 with sodium chromate at room temperature. Gentle alkaline hydrolysis of 1 gave the methyl ester of the natural acid 7. Compound 2 was isolated from the most polar frac- tions. This compound is an a&unsaturated dihydroxy ester (IR: 3400,1710,1640,1240 and 1050 cm-‘), and it has been described before as its acetyl derivative [2]. The hydroxyl group at C-6 was assigned #I-stereochemistry because of the coupling constants of its geminal hydro- gen. Oxidation of 2 with manganese (IV) oxide [3] gave the a&unsaturated hydroxyketone 8, whose ‘H NMR spectrum exhibited the signals of a methoxycarbonyl, a hydroxymethylene, three methyl singlets, a methyl doub- let and the grouping CO-CH=C, whose hydrogen ap- pears at 66.22 (lH, d, J =2.9 Hz). Acetylation of compound 8 afforded 9. Sodium chromate oxidation of 6 at 0” gave 9 (10% yield), the allylic oxidation product without double bond migration, and 1 (90%) confirming the position of the hydroxyl at C-6 [4]. When we tried allylic hydroxylation by treatment of 6 with N-bromosuccinimide, compounds 10 and 11 were obtained [5]. Compound 10 is an unsaturated hydroxy ester whose ‘H NMR spectrum showed the signal corres- ponding to the hydrogen atom geminal to an allylic secondary hydroxyl group (64.42, lH, m). The 13CNMR spectrum presented signals of six tetrasubstituted carbon atoms, two of these being olefinic (6126.6 and 162.3). Therefore, compound 10 possesses a tetrasubstituted double bond, produced by double bond migration and subsequent hydroxylation of 6. Compound 11 is an ester with two conjugated double bonds (IR: 1735, 1615, 1560 and 124Ocm-‘; UV a,,,_ 354 nm). The ‘H NMR spectrum showed the signals of two vicinal olefinic protons (66.35, lH, dd, J, = 3.2 Hz, 5,=9.7 Hz and 5.81, lH, dd, J, =3.2 Hz, J2=9.7 Hz). Its i3C NMR spectrum showed the presence of four olefinic carbon atoms (two methynes and two tetrasubstituted). The structure of methyl 15-acetoxy-6,8-labdiene-17-oate assigned to compound 11 corresponds to the dehydration product of 10. In contrast, on dehydration of 2 compound 12, the isomer of 11, was obtained. Compound 12 is also a hydroxy ester with two conjugated double bonds. Its ‘HNMR spectrum, in addition to the signals due to a methoxycarbonyl, a hydroxymethylene and two methyl groups (Table l), contained the signals corresponding to 401