Sesquiterpenolides from Melanoselinum decipiens

Pergamon PII: SOO31-9422(97)002549 SESQUITERPENOLIDES FROM MELANOSELINUM DECIPIENS GLIILLEKMOM. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA MASSANET.* FRANCISCO M. GUERRA, ZACAR~AS D. JORGE and CARMEN ASWR~;A Departamento de Quimlca Or&mica. Universidad de CBdiz, Apdo. 40, 11510 Puerto Real, Ciidlz. Spain Key zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Word Index Mc,/n77osr/inun7ckcipiens; Umbelliferae; sesquiterpene lactones: eudesmanolides. Abstract--Seventeen new eudesmanolides have been isolated from Mrlunosrlinutn decipiens, together with the previously known lasolide and the decipienins A, B. D and F. Relative configurations of decipienin B have been assigned by spectroscopic means. Cs 1997 Elsevier Science Ltd. All rights reserved INTRODI’CTIOh In the course of our research directed toward the isolation and structural elucidation of sesquiterpenolides from the Umbelliferae family [I], we have carried out a reinvestigation of Melanosdinutn dec,ipietz.s, a shrub endemic to Madeira Island. The genus Mrlatmrlinutt~ is included in the Luserpitieue tribe, a group of the Umbelliferae which has been shown to contain sesquiterpene lactones. This species was first investigated by Gonzilez et (I/., w,ho isolated eight sesquiterpene lactones named decipienin A-H [24]. In 1986. Holub et ui. [5]. on the basis of spectroscopic studies. corrected their structures. Recently. we have described the isolation and identification of two eudesmanolides from this species, with a particular stereochemical pattern, not found to date in this Family [I]. In this reinvestigation. I7 new sesquiterpenolides. belonging to the eudesmanolide class. have been isolated together with the previously known lasolide (16) [6-81 and the decipienins A (2). B (5). D (7) and F (8) [24]. We ha\,e assigned the relative stereochemistry of decipienin B by means of NOE measurements. NOE experiments led us also to confirm the relative stereochemistry of decipienin A. D and F. RESULTS AND DISCC’SSIOP. Compounds 14 exhibited very similar spectra. The IR spectra of 24 showed absorptions corresponding to a ;+lactone ring (I 79 I-1 795 cm ‘). an r,fl-unsaturated carbonyl group (1594 I663 cm ‘) and an T./& unsaturated ester (1713-I 718 cm ‘). Compound 1 * .4uthor to whom correspondence should be addressed. lacked the latter signal and showed an absorption at 3507 cm ‘, characteristic of a hydroxyl group. Mass spectroscopy revealed molecular ions at tn/z 262 for 1 and m/z 344 for 24. Their ‘H NMR spectra were closely related and revealed the presence of two vinylic protons, H-l and H-2. in addition to a doublet corresponding to the allylic lactone proton. Taking into account all of these data. we arrived at the basic structure of 1IX-hydroxy (or acyloxy)-3-0x06aH,7rH. 1Or. 11[j-dimethyleudes1,4-dien-6,12-olide for compounds 14. There were only changes in the signals of the ester groups [see Table I(a) and (b)]. Signals corresponding to H-6 and H-7 are affected by the presence of an ester group at C-l I. Such esterification deshielding by 0.7 ppm the signal of H-7 and 0.2 ppm that of H-6. This behaviour confirms the relative stereochemistry assigned to C-6, C-7 and C11. Though lactone 5 (decipienin B) was previously described [3]. no high resolution ‘H NMR data were available and the stereochemistry of the epoxide groups remained unassigned. We, therefore, reanalysed the spectra of this lactone [Table I(a) and (b)] and assigned the orientation of the oxirane rings by means of NOE measurements (Fig. I). Irradiation of the H-2 signal showed a positive NOE effect in H-l and H-3. confirming that these protons are at the same side of the molecule. Irradiation of H-l also produced an enhancement of the angular methyl signal. NOE interactions between the angular methyl, H-6 and H-7 were also observed. Compound 6 showed in its ‘H NMR spectrum [Table I(a) and (b)] the signals of a tigloyl group instead of the signals for the angelic ester. The remaining signals were nearly identical to those of 5. Compounds 7 and 8 showed IR absorption bands indicating a hydroxyl group, a y-lactone ring and an x,/?-unsaturated ester. The mass spectra showed a 1645 1646 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA G. M. MASSANETef ul. * * * I * aa.?! MCOQI * data for compounds zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 11 17,20 and 21 Table I(b). ‘H NMR spectral 11 H 1 3.38 s 12 3.39 d (1.7) 2% 13 4.90 dd (12.3,4.6) * 14 17 20 21 3.42 hr dd 3.64 hr d 4.62 dd 3.35 dd 3.83 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA dd 5.6 dd (11.3.4.4) (12.0,3.3) (12.6,5.7) (11.5.4.0) (11.5) * * * 1.62 m 2.67 dd 2.67 dd (12.6,S.S) (17.3, 12.6) * 28 16 15 2.77 dd (17.3,5.5) (17.3,12.6) 2.85 dd (17.3.5.7) 2.12 ddd (3aH) 3 (13.7, 13.6, 5.6) 2.35 ddd (3flH) (13.7,4.9,2.3) 2.87 d 2.89 d (11.1) 4.94 dd (11.1,8.3) 3.21 ddd (11.1) 4.94 dd 5 6 7 (8.3,6.6,6.6) 1.91 hr s 4.87 I (11.1.8.5) 3.23 ddd (3.0) 2.99 ddd (8.5,6.4,6.4) (11.1,5.9,3.4) 8ci 1.85 rn 1.87 m 1.20 m 8P 901 I .85 m 1.87 W I 1.80 m 2.21 M 2.23 m 2.13 rn 9B 1.23 m 1.25 m 1.80 M 14 1.88 s 0.87 .r 1.80 .F 0.88 .r 15 2.19 s 2.20 J 13 3’ 4’ 5’ 6.18 yy (7.2, I .S) I .99 dy 6.94 qq (7.2. 1.1) 1.82 d (7.2, I .6) (1.0) 1.88 dq (1.6, 1.5) OH Acetate * Overlapped 1.80 In J 1.90 s 6.13 qq (7.2. 1.6) 1.95 dq (7.2, 1.5) 1.85 dq (l&,1.5) I .94 s 1.60 s 1.57 s 0.73 s 0.95 s 5.04 br s (15aH) 4.93 br F(15bH) 6.15 qy (7.4.1.5) 1.98 dq (7.4, 1.5) 1.87 dq 6.17 qq (7.2, 1S) 1.97 dq (7.5,1.5) 1.87 dq (1.5,1.5) (1.5,1.5) 4.94 br d (15aH) (1.3) 4.78 hrd(lSbH) (1.3) 6.17 yy (7.4, 1.5) 1.99 dq (7.4, 1.5) 1.88 dq (1.5,l.S) 1.42 s 0.90 s 5,14brd(lSaH) 2.08 J 5.09d(l5aH) (1.4) 4.99 hr d (I 5bH) (1.4) 4.96 d(lSbH) (1.4) (1.4) 6.13 yy (7.2.1.4) 1.95 dq (7.2, 1.4) I .X5 dq (1.4,1.4) 2.61 hr s 2.04 s 1.67s 0.82 s 2.04 s I648 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA G. M. MASSANET et ul. 1 2 3 4 5 R=Ang 7 X=a-OH, P-H R=H IO x=0 8 R=Tig R=Ang R=Tig R=Sen zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA X 8 9 X=a-OH, x=0 B-H 11 12 R=Ang R=Tig 13 Xpa-OAC; 14 Xl=a-OH; 15 X,=P-OAc; XpPOH, a-H; R=Ang X2=0; R=Ang X2=0; R=H R .PAW H 0 % 0 18 I7 R=a-OH R=P-OH I8 I9 20 21 R=Ang, R’=Ac R=H, R’=Ac R=Ang, R’=H configurations were assigned by means of NOE molecular ion at ~7:: 364. in accordance with the experiments. molecular formula C&H,,O,. In their ‘H NMR specCompounds 9 and zyxwvutsrqponmlkjihgfedcbaZYXWV 10did not give a [Ml’ peak. The tra. signals corresponding to vinylic protons (7, 5.60, highest mass spectral fragment appeared at m/z 347. d. H-3; 6.00, dd, H-2: 8. 5.71. hu c/, H-3; 5.94 dd, H-2) corresponding to [M - Me]+. Their IR and NMR data were observed and a doublet at 6 3.49 was assigned indicated the presence of an a&unsaturated ketone to H-l (geminal to a hydroxyl group). The relative zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML (17 14. I684 cm ‘), a tertiary hydroxyl group (3390. 3371 cm ‘), a ;‘-lactone (1790, 1788 cm ‘) and an angelate group (1714, 1727 cm ‘). They showed in their ‘H NM R as more significant signals two doublets corresponding to the olefinic protons H-2 and H-3 (9, 5.93, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO d, H-2; 6.63, (/. H-3; 10. 5.91, d, H-2: 6.55, d, H3). The stereochemistry at C-4 was confirmed by NOE experiments. Compounds 11 and 12 showed a [M] peak at nziz 362 corresponding to the molecular formula C&H,,O,. de Their IR spectra contained signals corresponding to a ;*-lactone ring. an z&unsaturated ketone and a Fig. I. Observed NOE III decipinin B (5) Sesquiterpenolides I649 from Melunoselinum de ipiem hydroxyl group. The only significant difference in their ‘H NMR spectra was the position ofthe vinylic proton of the ester group, indicating the presence of an angelate group in 11 and a tiglate in 12. The presence of a narrow multiplet corresponding to the olefinic proton, H-3 (11, 6 5.91; 12, 6 5.92) can be observed in both spectra. The chemical shift of H-I is almost the same in both compounds, with the only difference being in their multiplicity, a singlet at ci 3.38 in 11 and a doublet at 6 3.39 (J,., = 1.7 Hz) in 12. The lactonic proton appears at the same position (6 4.94, dd) in both compounds. A displacement of 0.5 ppm upheld in the signal of H-l in relation to that in 7 is due to the p-oriented hydroxyl. Compound 13 was assigned the molecular formula CzzH,,O, (MS). It showed in its IR spectrum absorptions at 34 I I cm ’ (hydroxyl), 1788 cm ’ (;:-lactone) and 1722 cm-’ (angelate and acetate groups). Its ‘H NMR spectrum showed the presence of an allylic hydroxyl group (6 4.16. hr s. H-3). ‘HP’H COSY established the proton connections of the segment Cl:C-3. The position of the double bond between C-4 and C-5 was deduced from the presence of a methyl at 6 1.92 (s, 3H- 15) and from the multiplicity of the ring closure (d. 6 5.42, J(,,: = 4.3 Hz). The relative configuration at C-l and C-13 was determined by NOE measurements. Compound 14 showed a [Ml’ at mi-_ 362 corresponding to a molecular formula of C,,H?,O,. It exhibited IR spectral bands corresponding to a hydroxyl group (3454 cm- ‘), a ;:-lactone (1790 cm ’ ). an @unsaturated ester (1720 cm-‘) and an r$unsaturated ketone (1678 cm-‘). Its ‘H NMR spectrum resembled that of 13. Thus. the signals corresponding to an angelate moiety could be observed and the splitting pattern of H-6 was the same as that of 13 (d. d 5.53, J,,i = 4.7 Hz). There were. however, some differences. The “C NMR spectrum revealed the presence of a carbonyl group that was assigned to C3. In its ‘H NMR spectrum, there was a double doublet at (r 3.83 assigned to a proton geminal to a hydroxyl group. The splitting pattern of the former signal was only possible of that hydroxyl group was attached to C-l. The IR spectrum of 15 showed bands corresponding to hydroxyls (3446 cm -I). a ;N-lactone (1782 cm ‘), an acetate ester (1745 cm ‘) and an r&unsaturated ketone (1678 cm-‘). The downfield part of the ‘H NMR spectrum was very simple. Only a narrow doublet at 6 5.72 (.Jc,,i = 4.4 Hz) corresponding to the lactone ring proton and a double doublet of H-l (b 5.06, J ,,2z = 12.6 Hz. J ,.2,j = 5.7 Hz) could be observed. Other significant signals were those of H-22 (b 2.67, dd, &,, = 17.3 Hz. J-,, = 12.6 Hz) and H-2fi (6 2.85, &, JzB,, = 5.5 Hz). Compound 16. lasolide, was previously isolated from Laser trilnhutn [6-81. Together with 16. we have now isolated its C-l epimer. I-epi-lasolide (17). It showed in its mass spectrum a peak corresponding to [M + l]+ at m/z 349 and the fragment [M + I ~ H,O]’ at m/z 331. It presented an IR spectrum indicating a hydroxyl (3471 cm-‘), a ;t-lactone (1780 cm ‘) and double bonds ( 1649 cm- ‘). The presence of the angelate ester was clear. since its ‘H NMR spectrum contained a quartet of quartets at 6 6.17 (J3 .4 = 7.4 Hz; J, 5 = I .5 Hz). The signal of the lactone ring closure appeared at b 4.86 (CU. JG. = 11.7 Hz: J,,; = 9.6 Hz) between the two signals belonging to the exomethylene protons H-l 5a and H15b (hu d. ci 4.90. H-15a; hr d, fi 4.70, H-l5b). H-l appeared at b 3.64 as a broad doublet and its relative orientation was determined by NOE measurements. Irradiation of H-l produced an enhancement of the angular methyl signal. We described compounds 18 and 19 in a previous paper [I]. Both of them, together with 20 and 21, present a different stereochemical skeleton since they possess a a-oriented angular methyl. Compound 20 gave a [Ml+ peak at m:: 308. corresponding to the molecular formula C,?HZ405. This formula is made up of 15 carbons characteristic of the sesquiterpene skeleton plus two more carbons from an acetate group. The presence of this acetate moiety was confirmed by the presence in the mass spectrum of a peak at m/-_ 249 corresponding to the fragment [M - HOAc]’ The presence of this group was also confirmed by a singlet (3H) at b 2.04 and a double doublet at 6 4.62 that belongs to H-l. The value of the coupling constants J,,21 = 11.3 Hz: J,,,,, = 4.4 Hz indicated an a-orientation of H-l. The IR spectrum contained the bands of a hydroxyl (3416 cm-‘), ylactone ( 1777cm ‘) and an acetate group ( I 723 cm ‘). In the ‘H NMR spectrum, two exomethylene protons at (5 5.14 (hr d. H-15a. J,5,,ih = 1.4 Hz) and 4.99 (br d, H- 15b) were observed. H-6 appeared as a triplet at S 5.12 (Jh.5 = J,,: = 3.4 Hz) which partially overlapped with one of the exomethylene signals. The small value of the coupling constant of H-6 indicated a relative equatorial-axial disposition between H-6/H-5 and H6/H-7. confirming the different stereochemical pattern of this lactone from that of the previously described. Compound 21’s spectra resembled those of 20. The typical signals of the angelate ester (d 6.13, yy, zyxwvutsr J.14 = 7.2 Hz; J,.,, = 1.4 Hz) were observed in its ‘H NMR spectrum. Signals belonging to the two exomethylenic protons appeared at 6 5.09 ((1, H-15a, J ,ia.,5h = 1.4 Hz) and 4.96 (d, H-l 5b). The H-6 signal appeared at ci 4.87 (dd, J6,s = J,- = 3.0 Hz), 0.25 ppm upfield compared with the previous compound. The presence of a double doublet at ci 3.35 indicated the presence of an hydroxyl group. Its position at C-l was determined from the ‘HP’H COSY spectrum. The value of its coupling constants indicated that this hydroxyl was [&equatorial. This was confirmed by NOE measurements. EXPERIMENTAL Mps: uncorr.; HPLC: LiChrosorb (IO x 250 mm). flow rate 3 ml min-‘. Grrwra/. (Merck) Si 60 differ- G. M. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ MASSANET et zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP al. I650 Table 2. ‘jC NMR spectral data for compounds 2-5.9, 11, 14, 16. 19 and 21 C 2 3 4 5 11 21 9 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLK 14 16 19 I 2 3 4 5 6 7 8 9 IO II 12 13 14 15 I’ 2’ 3’ 4’ 5’ 155.5 126.0 185.8 133.6 151.5 79.1 46.0 20.4 40.1 41.8 80.1 173.9 19.3 26.4 12.0 166.2 126.8 140.8 15.9 18.6 155.5 125.9 185.8 133.7 151.5 79.3 52.3 19.1 40.0 41.9 ‘, 155.5 126.0 185.4 133.2 151.4 76.4 42.1 19.2 40.0 42.0 ‘1 173.5 18.4 26.6 I I.8 166.4 127.8 139.6 12.0 14.5 173.5 18.8 26.6 12.0 165.0 158.5 115.0 27.6 20.5 60.8 47.7 55.0 53.0 35.2 75.7 43.2 20.5 38.3 32.3 78.1 173.9 19.9 16.7 20.5 166.4 126.9 140.5 15.9 18.0 201.3 125.2 152.5 70.4 51.4 16.5 43.6 20.4 30.5 48.0 78.7 173.5 20.2 24.1 19.9 166.4 126.6 141.9 15.9 18.2 78.1 196.8 125.2 162.0 48.8 76.6 40.3 20.5 30.0 39.7 79.6 174.1 20.3 18.2 23.7 166.5 126.9 140.5 15.9 18.5 74.9 42.6 196.7 138.4 151.0 71. I 51.5 20.5 33.1 44.3 83.5 ? ‘? 10.8 17.5 166.2 126.5 140.4 15.9 17.9 78.2 31.4 34.0 140.3 ‘I 7i.o 49.3 20.3 37.8 40.0 79.6 1 26.7 1 I.4 110.4 166.3 127.2 140.3 15.9 18.2 AcO ential refractometer detector; EIMS: direct inlet. 70 eV; ‘H NMR: 399.95 MHz, CDCI,, signal of residual CHCI, centred at b 7.25 as int. standard; ” C NMR: 100.577 MHz. CDCl,, central signal at CDCI, at 6 77.0 as int. standard; CC and TLC: silica gel. Plant material. M elanoselinum decipiens was col- lected near Funchal (Madeira) in the summer of 1993 and was identified by Dr Susana Sa Fontinha. A voucher specimen (MADJ no. 02676) is deposited in the Botanical Garden of Madeira. Extraction and isolation. The dried aerial parts of M. decipiens (1.2 kg) were extracted with EtOH in a Soxhlet apparatus for 12 hr. affording 25 g of syrup. This crude material was chromatographed on a silica gel column and eluted with mixts of petrol and EtOAc of increasing polarity. Frs of 100 ml were collected and combined on the basis of TLC monitoring. These frs were further rechromatographed on silica gel columns and the products were purified by HPLC using the same eluants. 1 la- Hy droq,- 3- oxo- 6aH,laH,lOaM e- eudesm- I ,4dien- 6,12- elide (1). C15HiX04. [a]? -20.0 (CHCl,; c 0.10). IR $,‘,m,cm- ‘: 3507 (hydroxyl), 2937, 1795 (ylactone), 1659 (ketone); MS m/z (rel. int.): 262 [Ml+ (0.2), 218 [M-CO,](0.6) 191 (3.4), 165 (4.8). 149 (8.6), 123 (ll.O), 69 (71.5), 55 (100). I Ia - Tiglo~~lo.y v - 3 - 0x0 - 6aH,7aH, 1OaM e - eudesm - C2,Hz,0Z. [a]$’ + 7.9’ (CHCL,; c 0.29). IR vcz cm-‘: 2938. 1793 (y-lactone), 1713 (tigloyl ester), 1660 (a&unsaturated ketone); MS m/z (rel. int.): 345 [M + l]+ (2. I), 327 [M + 1 - H20]+ (1 .O). 245 [M+l-HOTig]+ (13.3). 201 [M+l-HOTig-COz]+ (20.0), 83 [C,H,CO]’ (lOO.O), 55 [C,H,]+ (35.8). 1,4- dien- 6,12- elide (3). 80.0 32.6 33.8 142.9 49.0 77.3 48.9 20.5 34.1 43.5 80.0 172.0 20.6 11.8 111.3 166.3 127.4 140.1 15.3 18.4 170.6 21.1 79.1 31.3 34.2 143.6 48.9 77.2 49.0 20.5 34.6 43.7 82.7 173.8 20.4 11.7 110.9 166.4 127.6 139.7 15.3 18.6 1 la- Senecio_y lox~- 3- oxo- 6aH,7aH,lOrM e- eudesmC,,H,,O,. [a]$ +28.3’(CHCl,; c 0.10). IR vtg cm-‘: 2944, 1793 (y-lactone). 1714 (senecioyl ester), 1657 (r&unsaturated ketone); MS m/z (rel. int.): 344 [Ml+ (1.6), 244 [M -HOSen]+ (24.0) 207 (100) 83 [C,H,CO]+ (53.7), 55 [C4H7]+ (11.1). 1,4- dien- 6,12- elide(4). 1la- Angeloy loxy - la.2a- 3a,4a- diepox~~- 5/?H,6aH, (5). C10H2606. [a]$ -31.6’ (CHCl,; c 0.62). IR viz cm-‘: 2936, 1784 (ylactone), 1717 (angeloyl ester); MS m/z (rel. int.): 363 [M+l]+ (0.2), 263 [M+l-HOAng]+ (1.71). 249 [M+ 1 -HOAng-Me]+ (2.57). 83 [C,H,CO]’ (lOO.O), 55 [C,H,]+ (70.2). 11 a- Tigloy loxJ,- 1/?,2/?-3/?.4~-diepoxy-5/?H,6aH, 7aH.lOaM e- eudesman- 6,12- elide (6). C,,H,,O,. [G(]? - 22.0” (CHCl,; c 0.20). IR vi; cm-‘: 2936, 1784 (ylactone). 1717 (angeloyl ester); MS m/z (rel. int.): 263 (M -OTig]+ (0.6) 262 [M -HOTig]+ (0.2), 248 [M-HOTig-Me]+ (0.35) 83 [C,H,CO]+ (85.9) 55 [C,H,]+ (75.4). 7aH.lOaM e- eudesman- 6,12- olide 1 la- Angeloy loxy - la,4/I-dihydro.xv- 5/IH,6aH,7uH, CZOHz806. [a]? - 15.3” (CHCl,; c 0.17). IR vz.E cm-‘: 3413 (hydroxyl). 2929, 1779 ()-lactone), 1721 (angeloyl ester), 1657 (double bonds); MS m/z (rel. int.): 364 [Ml+ (O.l), 349 [M-CH3]+ (0.2), 346 [M-H,O]+ (0.3), 265 [M -OAng]+ (0.8), 264 [M-HOAng]’ (l.O), 83 [C,H,CO]+ (66.3). 55 [C,H,]+ (40.1). lOuM e- eudesm- 2,3- en- 6.12- elide 11a- Angeloy loxy - (7). 1a,4a- dihy drory - 5~H,6aH,7aH, (8). C,,H,,O,. [ali (CHCI,: c 0.10). IR $,‘g cm-‘: 3371 (hydroxyl). 2929, 1782 ()-lactone). 1717 (angeloyl ester), 1658 (double bonds); MS m/z (rel. int.): 264 lOuM e- eudesm- 2- en- 6,12- elide - 56.0“ Sesquiterpenolides from zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML M elanoselinumdecipiens 1651 [M -HOAng]+ (O.l), 249 [M -HOAng-Me]+ (0.3) [M-OAc-Me]+ (0.4) 230 [M-OAc-Me-H,O]+ 231 [M-HOAng-Me-H?O]+ (0.4) 83 [C,H,CO]’ (14.5) 55 [C,H,]+ (10.7),43 (100). 213 (0.3), 1 la- Angeloy loxy - la- hy droxy - 5jH,6aH,7aH, [M-Me-2H,O]+ (0.2) 83 [C,H,CO]+ (100.0). 55 [C,H,]+ (96.3). lOaM e- eudesm- 4,15- en- 6.12- elide (16). C,,H,,O,. zyxwvutsrqp 1 la- Angeloy loxy - 4a- hy droxy - l- oxo- .5flH,6aH,7aH, blh5 -16.7’ (CHCl,; c 0.18). IR vt: cm-‘: 3476 lOaM e- eudesm- 2- en- 6,12- olide (9). C,,H,,O,. [r]h5 (hydroxyl), 2937, 1786 (y-lactone), 1720 (angelate), 1655 (double bond); MS m/z (rel. int.): 349 [M+ l]+ -25.3” (CHCl,; c 0.47). IR rzz cm-‘: 3390 (0.1) 331 [Mfl-H,O]+ (O.l), 249 [M-OAng]+ (hydroxyl), 2931, 1790 (y-lactone), 1714 (angeloyl (3.0). 83 [C,H;CO]+ (lOO.O), 55 [C,H,]+ (63.9). ester), 1714 (a&unsaturated ketone). 1682 (double lla- Angeloy loxy - lfl- hy drox_v- 5flH,6aH,7aH, bonds); MS m/z (rel. int.): 347 [M-Me]+ (0.2) 263 1OaM e- eudesm- 4.15- en- 6.12~elide (17). C,,H,,OS. [M-OAng]’ (1.7), 245 [M-OAng-H,O]+ (3.3) 83 [%I$ -1.4’ (CHCl,; c 0.22). IR vt: cm-‘: 3471 [C,H,CO]+ (100.0) 55 [C,H,]+ (91.7). (hydroxyl), 2939, 1780 (;j-lactone). 1714 (angelate), 1 la- Angeloy loxy - 4p- hy droxy - 1 - oxo- SbH,6aH,7rH. 1649 (double bond); MS m/3 (rel. int.): 349 [M+ l]+ 1OaM e- eudesm- 2- en- 6,12- elide zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (10). C,,H,,O,. [a];’ (2.25), 331 [M-t I -H,O]+ (0.2) 249 [M+ l-4.0’ (CHCl,; c 0.10). IR [r]ZE cm-‘: 3371 HOAng]+ (7.0) 83 [C,H,CO]+ (100.0) 55 [C,H,]+ (hydroxyl), 2922, 1788 (y-lactone). 1727 (angeloyl (52.4). ester). 1684 (a&unsaturated ketone), 1639 (double bonds); MS m/z (rel. int.): 347 [M-Me]+ (0.8). 263 [M-OAng]+ (2.7) 245 [M-OAng-H,O]+ (6.1). 83 [C,H,CO]+ (100.0). 55 [C,H,]+ (59.7). 11 a- Angeloy loxy - 1p- hy drory - 2- oxo- 5BH,6clH. 7rH, lOaM e- eudesm- 3- en- 6.12~elide (11). C2,H,,0,. [r]$ - 90.0” (CHCl,; c 0.35). IR v:G cm-‘: 3391 (hydroxyl): 2933, 1786 (y-lactone), 1717 (angeloyl ester), 1683 (ketone); MS m/z (rel. int.): 362 [Ml+ (0.3), 264 [M-C,H,,,O]+ (0.3). 262 [M-HOAng]+ (1.1) 244 [M-HOAng-H,O]+ (1.9). 83 [C4H7CO]+ (100.0) 55 [C,H,]+ (39.3). l1r- Tiglo~vlox~- l~- hy droxy - 2- oxo- 5~H,6aH,7aH, (12). C20H2h0,. [a]? -40.0’ (CHCl,; c 0.10). IR vz: cm-‘: 3391 (hydroxyl), 2933, 1788 cf-lactone), 1715 (tigloyl ester), 1685 (Q-unsaturated ketone); MS m/z (rel. int.): 362 [Ml+ (0.4) 347 [M-Me]+ (0.1). 264 [M-C,H,,O]’ (0.5). 262 [M-HOTig]+ (1.8) 244 [M-HOTig-H:O]+ (1.8) 83 [C,H,CO]+ (lOO.O), 55 [C,H,]* (86.9). 1a- Acetoxy - 11 a- angelo_vloxy - 3~- hvdroxy - 6aH, 7aH, lOuM e- eudesm- 4- en- 6.12- elide (13). C22Hi007. blh5 - 10.7’ (CHCl,; c 0.45). IR 1~2: cm-.‘: 3411 (hydroxyl), 2946, 1788 (;-lactone). 1722 (angelate and acetate groups); MS m/z (rel. int.): 347 [M -OAc]+ (0.2) 346 [M-HOAc]+ (1.0) 306 [M-HOAng]’ (0. l), 247 [M - HOAc- HOAng]’ (5.4) 246 [M-HOAc-HOAng]+ (19.0). 83 [C,H,CO]+ (100.0). 55 [C,H,]+ (25.6). lO xM e- eudesm- 3- en- 6,12- elide l1a- Angeloplox_v- 1a- h~~dro.u~~- 3- oxo- 6aH,7rH, (14). C&,H,,O,. [a];’ -18.0 (CHCl,; c 0.20). IR $,‘~ cm-‘: 3454 (hydroxyl), 2942, 1790 (y-lactone), 1720 (angeloyl ester), 1678 (a&unsaturated ketone); MS m/z (rel. int.): 362 [Ml+ (0.2) 344 [M-HzO]+ (0.5). 263 [M-OAng]’ (10.4) 262 [M-HOAng]+ (36.2). 83 [C,H,CO]+ (lOO.O), 55 [C,H,]+ (4.2). 1p- Acetoxy - 1 la- hy drox_v- 3- o_xo- 6aH.7aH, 1OaM eeudesm- 4- en- 6,12- olide (15). C,,HZ20,. [z]g +3.3’ (CHCl,; c 0.10). IR 1~::: cm-‘: 3446 (hydroxyl), 2934, 1782 (y-lactone), 1745 (acetate). 1678 (r&unsaturated ketone); MS m/z (rel. int.): 263 [M - OAc]+ (0.5) 248 lOaM e- eudesm- 4- en- 6,12- elide I/?- Acetoxv- 1 la- h~~drox~- 5aH,6aH.7xH,lO~M e(20). C,,H,,05. [r]r -97.5” (CHCI,; c 0.10). vzz cm-‘: 3416 (hydroxyl). 2938, 1777 (y-lactone). 1723 (acetate), 1657 (double bond); MS miz (rel. int.): 308 [M]+ (0.2) 264 [M-CO,]+ (0.7). 249 [M -OAc]+ (0.4) 83 [C,H,CO]+ (100.0) 55 [C,H,]+ (57.9). 1 la- Angelovloxv- l~- hy dro,xv- 5aH,6aH.7aH. lOgMeeudesm- 4,15- en- 6.12- elide (21). C,,H,,O,. [(IF - 11.9” (CHCL,; c 0.16). IR viz cm-‘: 3364 (hydroxyl), 2934, 1787 (;I-lactone), 1720 (angelate), 1657 (double bond); MS m/z (rel. int.): 248 [M -HOAng]+ (6.9) 83 [C,H,CO]+ (lOO.O), 55 [C,H,]+ (95.2). eudesm- 4.15- en- 6,12- elide Acknowledgement.s-Samples of M. deripiens were kindly provided by Dr Susana Sa Fontinha (Jardim Botanic0 da Madeira). The authors thank the CYCIT for financial support (PB93-0725). REFERENCES 1. Massanet. G. M., Guerra, F. M., Dorado, J. M., Jorge. Z. D. and Valerga, P., Phytochemistrv, 1995, 39, 1123. 2. Gonzalez, A. G., Breton-Funes, J. L.. Galindo, A. and Rodriguez-Luis. F., Anales Quimica, 1973,69, 1339. 3. Gonzalez, A. G., Breton-Funes, J. L.. Galindo, A. and Rodriguez-L& F.. Anales Quimica, 1974,70, 1028. 4. Gonzalez, A. G., Breton-Funes, J. L., Galindo, A. and Cabrera, I. Reuistu Latinoamericana Q&mica, 1976. 7. 37. 5. Holub, M. and Budesinsky, M.. PhJtochemistry , 1986.25,2015. 6. Holub, F., M., De Groote, Collection R., Herout, Czechoslotiak V. and Sorm, Chemic,al Com- munications. 1968, 33, 29 1 1. 7. Holub, M., Budesinsky, M., Smitalova, Z., Saman, D. and Rychlewska, U.. Tetrahedron Letters. 1984, 3755. 8. Holub, M., Budesinsky, M., Smitalova, Z., Saman, D. and Rychlewska, U., Collection Czechoslonak Chemical Communications. 1985, 51, 903.