Schkuhripinnatolides, unusual sesquiterpene lactones from Schkuhria pinnata

Phytochemistry,Vol. 29, No. 2, pp. 535-539, 1990. ‘Printedin Great Britain.

0

SCHKUHRIPINNATOLIDES, FROM

UNUSUAL

SESQUITERPENE

0031-9422/90 $3.00+ 0.00 1990 PergamonPressplc

LACTONES

SCHKUHRIAPINNATA U.

GANZER

and J.

JAKUPOVIC

Institute for Organic Chemistry, Technical University of Berlin, D-1000 Berlin 12, F.R.G. (Received 5 June 1989)

Key Word Index-Schkuhria

pinnata; Compositae; sesquiterpene lactones; schkuhripinnatolides.

Abstract-Schkwhria pinnata afforded, in addition to several known structures were elucidated by high field NMR spectroscopy.

INTRODUCTION

The genus Schkuhria comprises about 15 species and is distributed principally in the tropical areas of Central and South America. Few Schkuhria species have been introduced into Africa. Previously the genus has been placed in the tribe Helenieae; after the dissolution of the tribe it has been moved along with many other genera to the tribe Heliantheae, subtribe Chaenactidinae. Chemical investigations gave several acetylenic compounds [ 1,2], germacranolides [2-83, elemanolides [9-l l] and labdanes [12].

RESULTS AND DISCUSSION

The aerial parts of S. pinnatn yielded in addition to pectolinarigenin, loliolide, taraxasteryl acetate, schkuhrianol (1) [Z] and known sesquiterpene lactones 2 [13], hiyodori lactones C and B (5 and 6) [14, 151, 7 [3, 51, eucannabinolide (8) [3,5], 9 [6], schkuhrin II (10) [3], 11 [16], 12,13 and 19 [17], eight new ones, the germacranolides 3 and 4, unusual heliangolide derivatives named schkuhripinnatolides A-C (l&16), the melampolides 17 and 18 as well as the guaianolide 20. Comparison of the ‘H NMR spectral data of 3 and 4 with those of the known compound 2 suggested that they differed only in the nature of the ester side chain at C-8. Both compounds displayed signals for a dihydroxytiglate moiety (66.73 t, 4.99 br d and 4.40 br s) esterified at 4-position. The nature of these ester groups for 3 and 4 was deduced as 2hydroxyisovalerate and 2-hydroxy-3-methyl valerate, respectively, from decoupling experiments and mass spectral data (see Experimental). The ‘H NMR spectra of 14-16 were similar to that of schkuhrin II (10). However, the H-l and H-6 signals were shifted downfield (ca 0.4 and 1 ppm respectively). In the spectrum of 16 the signal for the methyl group at C-10 was replaced by a pair of signals at 6 2.44 dd (showing an allylic coupling to H-l) and 62.37 br d. Furthermore, signals were present representing an isopropyl group similar to that of 2-oxo-isovalerate portion of 9. However, the chemical shift of H-3” as well as the signal at 6 87.2 s for a oxygen bearing quaternary carbon in the 13C NMR spectrum of 16 suggested that C-14 was connected to

sesquiterpene

lactones,

eight new ones. The

C-2” of 2-oxo-isovalerate group of 9. The aforementioned chemical shift differences of H-l and H-6 are probably the result of the conformational changes due to the formation of the macrocyclic lactone ring. In order to prove this proposal a series of NOE difference spectroscopy experiments were carried out. The irradiation of H-3” signal clearly enhanced H-14 indicating the close spatial proximity of these two protons which is only possible by the connection of C-14 to C-2”. Examination of the model indicated that the preferred conformation is the one with the eight-membered Iactone ring above the plane of the carbocyclic ring. This also explained the downfield shift of H-6 because of its proximity to the oxygens at C-8, C-l” and C-2”. In that way H-7 and H-l came very close to each other, which was confirmed by their mutual NOE effects. The stereochemistry at C-2” followed from the NOE between OH and H-6. The unequivocal assignment of all signals was based on further NOE results and from the couplings observed. The structures of 14 and 15 differ from that of 16 only by the nature of the substituent at C-8. While in 14 a free hydroxy group was present, as followed from upfield shift of H-8, the ‘H NMR spectrum of 15 showed signals for 4-hydroxytiglate. We have named 14-16 schkuhripinnatolides A-C. The formation of 14-16 can be best explained as an attack of a A1’(14) isomer of the corresponding lactones of type 9 at the protonated cc-keto group of the 3/&acyloxy residue (see Scheme 1). The ‘HNMR spectrum of 17 displayed a typical melampolide signal pattern. The data were very similar to those of the corresponding 12,6-lactone which showed the coupling between H-8 and hydroxy group. A doublet of quartet at 62.55 for H-l 1 and a methyl doublet at 6 1.42 for H-13 indicated 11,13-dihydrolactone. In the ‘H NMR spectrum of 18 the aldehyde signal of 17 was replaced by a pair of doublets at 64.09 and 4.14. Thus, the corresponding alcohol was likely. In agreement with this, the signal for H-l was shifted upfield (Table 1). The NOE effects between H-l, H-14 and H-14’, between H-6, H-8, H-11 and H-15 as well as between H-13 and H-7 allowed the complete assignment of its stereochemistry. The corresponding 12,6-lactone has been isolated from Artemisia gupsacea [ 181.

535

U.

536

GANZER

and J.

JAKUPOVIC

)”

^-ofl(W2)&i

2 5

I Me0

HO

R’

5

6

7

6

AC

AC

H

AC

R2H

r:--_

&

::

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0

-OH

&OH

&OH

0

0

12

The structure of the guaianolide 20 also followed from the ‘HNMR spectrum which resembled that of 3-dihydro-4fi,lSdihydrozaluzanin C [19, 201 and differed only in the signals for the ester residue. Again 4-hydroxytiglate was easily recognized from the typical signals.

13

The new results agree well with those reported previously for members of the subtribe Chaenactidinae and again support the placement of Schkuhria in the latter subtribe. However, the chemistry of Arnica, also placed in the subtribe [21], is completely different.

Sesquiterpene lactones from Schkuhria pinnata

R

:

,,.%,-_.H a,, R

0

537

C:‘,

,,:“,,

0

19

20

Scheme 1. EXPERIMENTAL

The aerial parts of Schkuhria pinnata (200 g, collected in March 1989 about 15 km SW of Windhoek, Namibia, voucher 88/43 deposited in the SW Herbarium at Windhoek) were extracted with Et,O-MeOH-petrol (1: 1: 1). The extract was separated by CC (silica gel) into seven fractions [l: petrol; 2: Et,O-petrol (1:9); 3: EtzO-petrol (1:3); 4: Etzspetrol (1: 1); 5: EtzO; 6: Et,O-MeOH (7:3); 7: Et,O-MeOH (l:l)]. The fractions were further separated by TLC and/or HPLC (RP 8, MeOH-H,O, 3:2) affording the following compounds (final purification step for each new compound is given in parenthesis): 50 mg taraxasteryl acetate, 50 mg pectolinarigenin, 10 mg loliolide, 300 mg schkurianol 1, 10 mg 2, 5 mg 3 (HPLC, R, 7.2 min), 5 mg 4 (HPLC, R, 8.4 min), 10 mg 5,50 mg 6, 10 mg 7,50 mg 8, 40 mg 9,50 mg lo,20 mg, 11,5 mg 12,5 mg 13,5 mg 14 (HPLC, R, 16.5 min), 5 mg 15 (HPLC, R, 17.4 min), 10 mg 16 (HPLC, 11.2 min), 10 mg 17 (HPLC, R, 5.1 min), 10 mg 18 (HPLC, R, 4.9 min), 50 mg 19 and 10 mg 20 (HPLC, R, 6.2 min). 3B-Hydroxy-8B-[S’-hydroxy-4’-(2”-hydroxyisoua~eroy~oxy)tigloyloxy] costunolide (3). Oil; CIMS m/z (rel. int.): 479 [M + 11’ (3), 361 [M -(Me),CHCH(OH)COOH + 11’ (20), 247 [M RCOOHfl]’ (50), 229 [247-HzO]+ (70), 119 (100). 3~-Hydroxy-8~-[5-hydroxy-4’-(2”-hydroxy-3”-me~hy~ oaleroyloxy)-tigloyloxycostunolide (4). Oil; MS m/z (rel. int.): 360 [M - EtCH(Me)CH(OH)COOH]+ (0.6), 246 [M - RCOOH] + (8),

228 [246-H,O]+ (lo), 115 (40), 97 (52), 76 (100). Schkuhripinnatolide A (14). Oil; IR v$$’ cm-‘: 3400 (OH), 1770 (y-lactone), 1745 (CO,R); CIMS m/z (rel. int.): 363 [M + 11’ (8), 345 [M -Hz0 + l] + (14), 247 (20), 229 [345 -C,H,O,] + (100). Schkuhripinnatolide B (15). Oil; IR ~2:: cm-‘: 3400 (OH), 1775 (y-lactone), 1745, 1710 (CO,R); CIMS m/z (rel. int.): 461 [M+ 11’ (0.5), 345 [M-RCOOH+ 11’ (lo), 229 [345 -C,H,O,]+ (100). Schkuhripinnatolide C (16). Oil; IR vz$> cm-‘: 3400 (OH), 1770 (y-lactone), 1745, 1715 (COOR); CIMS m/z (rel. int.): 459 CM-H20+1]+ (1). 345 [M-RCOOH+l]+ (lo), 229 [345 -CSHBOB]+ (100); ‘%NMR (CDCI,, C-1-C-15): 127.6 d, 29.3 t, 79.8 d, 137.6 s, 130.2 d, 76.0 d, 47.1 d, 74.8 d, 44.7 t, 135.7 s, 134.1 s, 166.2 s, 124.7 r, 46.0 t, 22.9 q; C-l’C-5’: 170.3 s, 132.0 s, 145.5 d, 56.4 t, 59.1 t; C-1”Q.Z-5”: 175.8s, 87.2s, 32.6d, 18.0 q, 15.7 q. 6a-Hydroxy-14-ox0-11~H,4E,1(10)E-germacradiene-8,12olide (17). Oil; IR vL’$ cm-‘: 3460 (OH), 1785 (y-lactone), 1725, 17OO(C=C-CHO); MS m/z (rel. int.): 264.136 [M]’ (1) (talc. for C,,H,,O,: 264.136), 246 [M-HzO]+ (2.2), 212(40), 168 (loo). 8a,l4-Dihydroxy-1 l/?H,4E,l(lO)E-germacradiene-8,12-olide (18). Oil; MS m/z (rel. int.): 248.141 [M]’ (6)(calc. for C,5H,,0,: 248.141), 230 [M -H,O]+ (8), 109 (70), 84 (100).

br dd br br br dd

br dd br br br dd

1.51 br s

d t d br s d m ddq ddq t d

1.50 br s

d t d br s d dqq d d

14

15 OR

br d d qq d br s (OH) br s (OH) 2.34 1.82 2.23 0.95 0.87 6.80 4.31 1.81

br d d qq d d tq br d dt

5.77 d 2.45 dd

5.64 d 2.49 br dd 2.60 1.81 2.33 1.03 4.32 4.03

6.37 d

6.37 d

dq dd br s ddd dd br dd

5.35 7.08 3.13 5.28 2.68 2.83

5.36 6.92 2.92 4.08 2.57 2.69

dq dd dddd br s dd ddd

5.05 dd dq dd br s br s dd ddd

2.37 1.82 2.26 0.95 0.89 7.02 4.43 4.39 4.32 dd dd br s

t

br d d qq d d

5.77 d 2.44 dd

6.36 d

5.33 7.17 3.14 5.31 2.68 2.87

5.04 dd

5.61 br dd 2.82 ddd 2.17 ddd

16

m br d dd ddd ddd br dd br dd

1.74 5.13 4.28 1.88 3.73 2.77 2.66

1.69 d

9.50 d

1.42 d

br dd m m m

17 (570);

m br d dd ddd m br d br dd

1.73 5.28 4.45 2.01 3.65 2.82 2.35

4.09 br d 1.63 d

4.14 br d

1 1.42 d

br dd dddd dddd m

1st 5.55 2.31 2.17 2.45

400 MHz, a-values)

6.55 2.60 2.45 2.45

3, 4, 14-18 and 20 (CDCI,, 15

5.63 br dd 2.81 ddd 2.18 ddd

5.05 dd

5.58 br dd 2.80 ddd 2.15 ddd

14 (57”)

1. ‘H NMR data of compounds 202

ddd dd dddd ddd br dd dd

4.83 1.31 6.72 4.35 1.78

br s d tq br d dt

5.66 d 4.99 br s

6.35 d

2.31 4.56 3.31 5.72 2.51 2.73

3.10 br ddd 2.63 dd 2.53 ddd

*H-l1 2.55 dq; tH-11 2.57 dq; $H-4 2.38 ddq. J[Hz]:Compounds3and4:1,2a=4;1,2~=2a,2~=13;2a,3=6;2~,3=10;5,6=10;5,15=1;6,7=8.5;7,8=2;7,13=3.5;7,13’=3;8,9a=4.5;8,9~ =2;9~,9/?=15;compounds14-16: 1,2a=10; 1,2p=8; 1,98=1; 1,14=2;2a,2~=14;2~,3=5;2~,3=1.2;5,6=10;5,15=1.5;6,7=2.5;7,8=1;7,13 =2.8;7,13’=2;8,9~=3;8,9~=4;92,9~=14.5; 14,14’=15;compounds17and18: 1,2=10; 1,2’=7;2,2’=2,3’=13;2,3=5;2’,3=2’,3’=4;5,6=6,7 =7,11=10;5.15=1:8.9=5;8,9’=4.5;9,9’=15.5;11, 13=7;compound17;9a,14=1;compound18:14, 14’=13;compound20:1,2a=1,5=8.5;1,2~ =3; 2x,2/i’= 19; 2@,4= 1.5; 4,5=4, 15=7; 5,6=6,7=9; 7,8=2; 7, 13=3.5; 7, 13’=3; 8, 9c(=4; 8,9fi=3; 9a,9fi= 14.5.

1.80 6.72 4.99 4.40 4.24 1.83 1.53 1.32 0.96 0.81

5.63 d

5.63 d

1.80 6.73 4.99 4.40 4.07 2.08 1.03 0.87

6.33 d

6.33 d

13’

ddd s dd

13

ddd s dd

4.84 5.19 2.93 5.82 2.85 2.34

5 6 7 8 9a 9B

d

4.36 dd

4.36 dd

3

4.84 5.19 2.93 5.82 2.85 2.33

4.94 br dd 2.51 br ddd 2.33 ddd

4.94 br dd 2.51 br ddd 2.34 ddd

1 2a 28

d

4

Table

3

-.._

H

__

Sesquiterpene

lactones

8~_(4’-Hydroxytigloyloxy)-3-dehydro-4~,15-dihydrozaluzanin C (20). Oil; IR v z?$ cm- ‘: 3440 (OH), 1780 (y-lactone), 1745 (C =0), 1720(C=C_C=R); MS m/z(rel. int.): 360.158 [M]’ (S)(calc. for C,,H,,O,: 360.157), 244 [M-RCOOH]+ (24). 99 [RCO]’ (lOO), 71 [99-CO]’ (62).

REFERENCES

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from Schkuhria

pinnatn

539

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Robinson,

H. (1981) Smithsonian

Contr.

Botany

51, 84.