Sesquiterpene lactones from Artemisia ludoviciana

Phyrochemisrry. Vol 30, No. 5, pp. IS73 1577. 1991 Pnntcd in Great Britmn.

SESQUITERPENE J.

JAKUPOVIC,

c

LACTONES

FROM ARTEMZSIA

0031-9422/‘91 53.00+0.00 1991 Pcrgamon Press plc

LUDO VZCZANA

R. X.TAN, F. BOHLMANN, P.E. BOLDT* and Z. J.JlAt

Institute for Organic Chemistry, Technical University of Berlin, D-1004 Berlin 12, Germany; *Grassland, Soil and Water Research Laboratory, Temple, TX 76502, U.S.A.; TDepartment of Chemistry, Lanzhou University, Lanzhou-730000, P.R. China (Receiued

in

revised firm 20 September 1990)

Key Word Index-Artemisia [udouiciana; Compositae; sesquiterpene lactones; germacranolides; eudesmanolida; guaianolides; secoguaianolides; monoterpenes; hydroperoxide rearrangement.

Abstract-The

aerial parts of Artemisia ludooiciana afforded, in addition to more widespread compounds and several known sesquiterpene lactones, three new germacranolides, two guaianolides, four secoguaianolides and a monoterpene. A new rearrangement of a hydroperoxide is described. Structures were elucidated by high field NMR techniques.

INTRODUCTION

Artemisia

ludouiciana

Nutt. and some subspecies have been investigated chemically by different groups [l-93. In addition to eudesmanolides, guaianolides have been isolated. Furthermore, several monoterpenes [S, 8,9] as well as acetylenic compounds have been reported. We now have re-examined the aerial parts of this species.

RESULTS AND DISCUSSION

The aerial parts of A. ludouiciana afforded camphor, borneol, vannillyl alcohol, naringenin, the monoterpenes 26 [IO], 27 [ll], 28 [12], 29 [12] and 30, the jonone derivatives 24 and 25, the germacranolides 1 [ 13],2 [ 143, 3 [ 13],4 [ 133 and !G7, the eudesmanolides 8 [ 13],9 [ 143, 10 [ 151and ridentin B [16], the guaianolides rupicolin A andB[17],rupinA[18],11[13],13[19],14[6],15[20], 16 [19], 17 [19], 12, 18 and 19 as well as the secoguaianolides 20-23. The structure of 5 followed from its ‘H NMR spectrum (Table 1) which was similar to that of 4 [ 133. A singlet at 67.96 indicated the presence of a hydroperoxide. Spin decoupling showed that this oxygen function is at C-l and the configuration was deduced from the couplings which were identical with those of 4. The singlet at 67.80 in the spectrum of6 (Table 1) again required a hydroperoxide. The ‘H NMR data were nearly identical with those of the corresponding lz-hydroxy derivative [13], thus, the stereochemistry is the same. The ‘H NMR spectrum of 7 (Table 1) was in part very similar to that of the corresponding 3-desacetoxy derivative [21]. The additional acetoxy group led to a further low field signal at 6 5.42 (br dd). Spin decoupling required a 3acetoxy derivative. The configuration was deduced from the couplings of H-3, as well as from the observed NOES which further showed that both H-14 and H-15 are above the plane [H-6 with H-15 (6%); H-3 with H-5 (6%), H-l (3%) and H-2a (5%); H-5 with H-3 (7%) and H-l (4%), H-14 with H-8fi (5%) and H-15 (4%)]. mm

30:s.0

The ‘HNMR spectrum of 12 (Table 1) differed from that of 11 [13] mainly by the replacement of the exomethylene proton signals by those of an olefinic methyl and an olefin proton. As the H-8 signal was, as expected, shifted downfield all data agree with the corresponding A9 isomer of 11. The configuration at C-4 was again established by the observed NOE’s [H-15 with H-6 (8%), OH with H-5 (3%)]. The lactones 16 and 17 could be separated after acetylation. The ‘HNMR spectra of the resulting products (Table 1) indicated that the expected acetates are not formed though the molecular formulae calculated for C,9H,,0,. Spin decoupling led to sequences which also agreed with the expected diacetates. However, in the 13CNMR spectra (Table 2) the C-l singlets were at 6 113.6 and 113.0, respectively, indicating an acatylic carbon. For comparative purposes the 13C NMR data of rupicolin A diacetate are included in Table 2. All data required the presence of the rearranged lactones 16a and 17a. The observed NOES of lactone 17a established the stereochemistry [H-14 with H-9 (8%), H-6 with H-8 (7%), H-7 with H-5 (8%), 1-OAc with H-2 (2%) and 8-OAc with H-13’ (3%)]. The formation of the lactones 16a and 17a could be explained by attack of an acetyl cation at the hydroperoxide followed by insertion of oxygen in the l,lO-bond and subsequent addition of the acetoxy ion from the backside (see Scheme). To our knowledge this rearrangement has not been observed so far. The ‘HNMR spectra of 18a and 19a (Table 1), obtained by acetylation of the natural diols, showed the same splitting pattern. All signals could be assigned by spin decoupling, thus leading to the proposed structures. The spectra differed only in small shift differences of most signals. The most pronounced shift differences of H-2 and H-5 are almost certainly due to epimeric configuration at C-2. This and the remaining stereochemistry was proved by NOED. In the case of 18a effects were observed between H-14, H-2 (8%) and H-9b (6%), between H-5 and H-7 (5%) as well as between H-8 and H-6 (8%). The observed downfield shift of H-5 in the lactone 19a can be explaine by a Za-hydroxy group.

1573

1574

J. JAKUFQVIC et al.

A ‘OAc

AcO

2 X

0

4

3 “,a-OH

-5

“$-OH

H$-00”

AcO

OAc

HO

u X

9

CH,

IO

Me. a-0”

‘6 X

13

14

H,

0

The ‘H NMR spectral data of the inseparable mixture of 21 and 22 (Table 1) were in part very similar to those of a seco-guaianolide from other Artemisia species [22, 231. Spin decoupling allowed the assignment of all signals and the disclosed sequence showed that an additional hydroxy group is at C-8. As these lactones are probably biosynthesized from guaianolides like 13, the configuration at C-8 should be the same. The ‘H NMR spectrum of 20 (Table 1) differed from those of21j22 by replacement of the lowfield signal of H-3 by a two proton multiplet at 62.59 which coupled with a multiplet at 62.38 (H-2) and the olefinic methyl. The ‘H NMR spectrum of 23 (Table 1) indicated the presence of an isomer of 21/22 with a 2,3-double bond and a hydroxy group at C-4. A strong NOE between H-15 and H-5 (10%) as well as between OH and H-6 (4%) required a 4x-methyl configuration. We have named the lactones 2(r23 arteludovicinolide A-D. The structure of 3Oa, obtained by acetylation of the natural ketone, followed from its ‘H NMR spectrum (Experimental). Spin decoupling led to a sequence which

agreed only with the presence of the diacetate of 2,6dihydroxy-dehydrocarvomenthone. The stereochemistry follows from the NOES [H-7 with H-52 (5%) and H-3 with H-8 (7%) and H-9/10 (5%)]. The absolute configuration was not determined. The chemistry of this A. ludouiciano collection differs considerably from those of previous investigations [l-9] which, however, also were not uniform, although always reported were eudesmanolides and guaianolides. EXPERIMENTAL

The air-dried

aerial parts (40Og, collected in October

1988,

Hwy US 190, San Saba County, 6 miles west of Richard Springs, Texas, voucher Boldt 34776, deposited at the Herbarium University Et@petrol

of

Texas

(1 : 1:

at

Austin)

1).Theextract

were

extrd

with

was sepd first by CC (silica gel).

CC frs were combined to give 4 frs. The first contained camphor (Et,Gpetrol,

while

the

I :4).

second

of the

MeOH-

gave

17mg

borneol

The thud afforded by HPLC

ca 100 bar, flow rate 3 ml min. ‘. MeOH-H,O.

mainly

by

TLC

(always RP 8, 3: 2) 5 mg 1,

Sesquiterpene

lactones

from Artemisioludouiciuna

1575

0

0

‘d

18 2a-OH 19 2P-OH

24

28 la-OH

30

29 I@OH *10a,13a-15a,18a,l9a,Z4a-27a and 30a are the correspondmg LLAc,l2Ac. 28Ac and 29Ac are the monoacetates.

IOmg 16 and 17 as well as a mixture which gave 3 mg 13a, 2 mg Ma, 1 I mg rupicolin A diacetate and 4 mg 1% by acetylation followed by TLC (Et,O-CH,CI,-petrol, I :4:5, x 5). The most polar fr. was sepal into four parts (4:‘14/4) by flash chromatography (silica gel, 9 3-p). HPLC of 4/l (MeOH-H,O, 3:2) yielded 18mg rupicolin A and B, as well as a peak which gave mainly I2 mg 28Ac and 29Ac by acetylation followed by TLC (Et,O-CH,CI,-petrol, I :5:4, x 3). HPLC of412 (MeOH-H,O, I : 1) atforded two frs. The first was acetylated and then sepd by TLC (Et,O-CH,CI,-petrol, I :4: 5, x 4) to yield 2 mg 25a, 3 mg 26a, 2mg 3Oa (R, 0.63) and naringenin triacetate. The second gave 1mg IOa, 2 mg 15a, 1 mg 24a, vanillyl alcohol diacetate and 5 mg 27a by acetylation followed by TLC (Et@-CH,Cl,-petrol. 3:8: 10. x4). HPLC of413 (MeOH-H,O, 1: I) afforded three frs (4/3/l-4/3/3). The first was acetylated and then sepd by TLC (Et@-CH,CI,-petrol, I :4:5, x 5)togive2mg l!Ja(R,0,69)and a mixture which gave 2mg ridentin B diacetate and 2mg 18p (R, 0.71) by TLC (Et,OCH,CI,-petrol, 1:5:5, x6). TLC of 4/‘3/2 (MeOHCH,CI,, 3:97. x 2) afforded 5 mg 7 (R, 0.88). IOmg 8 and a mixture which yielded 3mg 5 (R, 0.26). 2mg 6

peracetates

while

(R, 0.33) and 4 mg 2. TLC of 4/3/3 gave 3 mg 3, 2 mg 4 and a complex mixture. HPLC of 4/4 (MeOH-H,O, 1: 1)afforded two frs. The first one was sepd by TLC (MeOH-CH,CI,, 1: 24, x 4) to yteld 2 mg 20 (R, 0.68), 2 mg 21 and 22 (R, 0.29), 3 mg 23 (R, 0.45) and II mg rupin A while the second gave by TLC (MeOHCH,CI,, 7:93, x 4) 6mg 9 and a band which afforded 3 mg 11AC and 3 mg l2Ac (R, 0.09) by acetylation followed by TLC (Et,O-CH,Cl,-petrol, I : 3: 3, x 5). Known compounds were identified by comparing their 400 MHz ‘H NMR spectral data with those of authentic samples. 38,13-Dhcetoxy-l8-hydroperoxygermacro-4E, 7( 1 l), 10(14brriene- 12.6%~elide (5). IR v 2: cm _ ’ : 1780 ( y-lactone), 1750 (OAc); MS m/z (rel. int.): 320.126 [M-HOAc]+ (18) (talc. for C,,H,,06: 320.126). 302 [320-H,O]+ (16). 260 [320 -HOAc] * (71), 242 [36C-H,O]+ (46), 109 (84), 60 (100). Treatment of 5 with A@-pyridine (24”, 19 hr) gave 2, identical with the natural compound (‘H NMR). 38, I3-Diacetoxy- la-hydroperoxygermacra-4E,9Z.7( 11 )-triene12,6a-elide (6). IR ~2: cm- ‘: 1775 (y-lactone), 1745 (OAc); MS m/z (ml. int.): 321 [M -OAc]+ (5), 320 [M - HOAc]+ (2),

2.08 m 1.53m 4.83 br d 4.75 hr d

5.31 m

4.90 brd

4.82 hr d

3.32 ddd 2.35 m

2.64 In

1.91 m

9

9

1.95 d 2.11 s 2.06 S

1.75dd 1.85 d 2.10s 2.07 s ..

]

2.43 dd

2.44 dd

5.19 hrd

2.65 brdd

5.72 dq

}

4.10 dd 2.77 dddd 5.08 ddd

4.15dd 2.77 dddd 5.12 ddd

4.21 dd 4.38 dddd 5.01 ddd

4.38 dd 3.81 dddd 4.94 ddd

4.19 dd 4. I2 dddd 5.26 ddq

1.26s 2.15s

1.89 m 2.12s 2.07 s

4.61 hrs 1.89 brd 2.09 s 2.03 s

1.96 brs 2.04 m 2.12s 2.0x s

} 1.33s 2.06 m 2.13 s 2.03 s

1.38s

5.60 d

5.84 dd

5.74 d

5.73 d } l.lYdd

5.65 d

6.20 d

6.36 dd

6.31 d

6.32 d 4.82 d

6.23 d

2.20 dd

2.58 br dd

2.29 dd

3.26 hr d

5.67 m 2.96 br d

2.67 d

5.50 ddq

5.81 dq

5.15 brd

1%

3.03 hrd

5.65 m

1Sa

3.06 hrd

3.05 ddq 2.94 hr ddq

3.09 ddq

17s

}

12Ac. 16a -19s and 20 23 (400 MHq

2.96 ddq

1Q

57.

5.47 ddq

5.84 d

6.00 d

12Ac

data of compounds

2.16s

2.18 s

2.20s

5.73 d 2.20s

6.41 d

2.63 m

2.79 m

6.41 d

}

}

4.71 brdd

4.71 hrdd

2.18 s

1.60s

2.21s

5.76 d

5.73 d }

6.44 d

6.41 d

2.20s

2.59 dd

2.69 dd

4.49 dd 3.66 dddd 4.26 ddd

2.41 d

7.48 d

6.16 d

23

2.63 m

2.75 m

5.23 brd 3.21 m 4.29 m

+

5.24 br d 3.24 m 4.29 m

2.28 dd

+

22

2.33 dd

21 -1

b-values)

5.74 d

2.65 d

5.25 hr d 3.27 m 4.27 hr dt

2.59 m

2.38 m

201

CDCI,,

22:2.3=2.5;2’,3-lO);compoundU:2,3=6;5,6=X.5;6,7=7,13=X.9’=2.5;7.8=5;8,9=9.5:9.9’=~7.5.

J [Hz]: Compound 5: 2,3=8,9 = IZ; 2’.3 -4; 5,6= IO; 8,X’= 15; KY’= 3: 9. 14== 1.5; compound 6: l,2- 11: 1.2’ --X,9- 5.5; 2,3=5,6= 10.5; 2’.3 =6; 5, 15 = 1; f&g’= 13. 13’~ 13; X’,9=12;8,14=9,14-l.kcompound7: 1,2=2; 1.2’:2’.3=11;2,2’=13.13’=13.5;2,3=6; 5.6=10; 5,15=1,2;compound 12A~:2,3~-8,9--6; 5,6=6,7=7,8=1();7,13=3.5, 7,~3’=3;8,14=9.14=1.5;compound16a:2.2’=18;2,3 -2’.3=7.13’=2.5;3,15=1.5;7,8=10:6,7=8.9=6.5;7.13=3.5;~,9’=4;9~9’~~6;~4,~~~~.5:compou~d~~a:2,~~~6; 2,3~2’,3=3,~5=1.5;5,6=I1;6,7=4.5;7,8=12:7,13=7.l3’=2.5.~.9=5.5;8.14=1; 13.13’~1.5:compounds l&and 19~ 5,6=6,7=7,X=8,9’=10.5;7,13-7,13’-R.9~3; 9.9’ = 14.5 (except 18~ 8,9 = 3.5; l!k 2.3 = 2); compound 20: 6.7 : 4; 7.8 = 8,9 .-- 6: 7. I3 T 7. 13’ = 2.5; compounds 21 and 22: 6,7= 4; 7, I3 = 7, I 3’ = 2.5 (cxccpt 21: 2.3 = 10: 2’. 3 = 2.5;

+ Overlapping multiplets. lOOH: 7.96 s. tOOH: 7.80 s. SOH: 3.48 brs.

1.78 brs 2.08 s 2.06 s

15 OAc

.._

5.35 br d 5.16 brs

14 14

13’ } 1.27s

3.10 m 2.49 m

3.37 br ddq 3.00 br dd

5.45 br d

6 7 8 8

}

5.51 hrd

5.22 brd

5.14brd

5

(2H)

5.42 hr dd 4.94 hr d

5.21 hrdd

5.49 hr d

5.21 dd

3

4.82 hrs

I.15 brdd

2.10 m

2.00 ddd

2’

I3

2.42 ddd

2.00 -

2.26 ddd

._

2.51 dd

4.57 hrdd

4.u) m

7

6t

I

5*

I. ‘H NMK spectral

2

H

Table

e

Sesquiterpene lactones from Artemisia ludouiciann Table 2. 13C NMR spectral data of compounds 16a, 17r and rupicolin A acetate (100.6 MHL CDCI,, d-values) C

1Q

178

I

113.6s 37.4 t 123.4 d 136.2 s 60.3 d 79.2 d 45.6 d 73.7 d 41.1 t 152.6 s 139.8 s 124.3 t 104.6 t 17.6 q 169.8 s 168.8 s

113.0 s 37.3 t 123.0 d 135.6 s 61.46 80.2 d 42.9 d 72.3 d 111.9 d 153.7 s 141.1 s 125.9 t 20.9 q 17.9 q 170.1 s 169.1 s (2 x C)

2 3 4 5 6 7 8 9 10 11 13 14 15 -C=o

168.7 s 22.2 q OAc

2l.Oq

22.5 q 22.3 q

Rupicolin A-diacetate 88.9 s 42.9 t 123.1 d 137.4 s 59.4 d 78.3 d 44.1 d 72.1 d 123.0 d

139.9 s 140.3 s 122.5 t 21.2 q 16.6 q

1577

[M-HzO)’ (9) (talc. for C,,H160.+: 260.105), 218 [260 -CzHzO]+ (41), 192 (42), 150 (100). 91 (52). Arteludouicinolide B and C (21/22). The epimers were not separated. IR v~~~‘~cm-‘: 3600 (OH), 1770 (y-lactone), 1710 (C=CC=O, 0); MS m/z (rel. int.): 276.100 [M -H,O]+ (14) (talc. for C,sH,60s: 276.100), 234 (86). 216 (48), 208 (70), 190 (78). 163 (lOO), 121 (84), 111 (86), 96 (98). Arteludovicinolide D (23). IR ~E$‘~crn- I: 3580 (OH), 1770 (y-lactone), 1717 (C==C-C=O, C=O); MS m/z (rel. int.): 277 [M -OH]+ (18) (C,sH,,Os), 259 [277-H,O]+ (8), 208 (24). 190 (24), 165 (42), 111 (100). 98 (83). 94 (70), 69 (50). 1/7,6a-Dihydroxy-3.4dehydrocarvomethone (30). Isolated as its diacetate 3op, IR vz: cm- ‘: 1760 (OAc), 1700 (C=CC=O); MS m/z (rel. int.): 208.110 [M -HOAc]’ (6) (talc. for C,,H,,O,: 208.110),166[208-ketene]‘(lOO), 123[166-CJH,]+(67).110 (98). 95 (64); ‘H NMR (CDCI,): 65.98 (dd, H-3). 2.45 (ddd, H-Sa), 2.67 (dd, H-S/?), 6.02 (dd, H-6). 1.38 (s, H-7). 2.45 (dqq, H-8), 1.13, l.l2(d, H-9, H-lO),J [Hz]: 3,52=1;3,8=2; 5a,5b=17.5; 5a,6 =10.5; Sfl,6=6; 8,9=8, 10=7.

170.1 s 170.0 s 169.3 s 25.0 q 21.8 q

260.105 [320-HOAc]’ (19)(calc. for C,,H,,O*: 260.105), 121 (47). 109 (68), 95 (72), 91 (100). 3~,13-Diocetoxy-l~,lOa-epoxygermacrcl-4E,7(1 I)-diene-12,&zelide (7). IR vzr; cm-‘: 1780 (y-lactone), 1755 (OAc); MS m/z (rel. int.): 304.131 [M-HOAc]+ (5) (talc. for C,,H,,O,: 304.131). 262 [304-ketene]’ (20), 244 [262-H,O]+ (26). 135 (51), 122 (50). 109 (100). 1~4a,8a-Trihydroxyguaio-2,9,11(13)-triene-l2,6or-olide (12). IR Y:$ cm-‘: 3600 (OH), 1770 (y-lactone); MS m/r (rel. int.): 305 [M-Me]+ (1). 260.105 [M-HOAc]+ (2.5) (talc. for CIsH,,Od: 260.105). 242 [260-H,O]+ (2.5). 227 [242-Me]’ (2.5), 200 (lo), 58 (100). Rearrangement of 16 and 17. The mixture of compounds 16 and 17 was treated with Ac,O-pyridine at room temp. for 16 hr. Usual work-up and TLC (Et,O-CH,Cl,-petrol, 1:4:5, x4) afforded the acetates 160 and 170. Compound 16a. IR vE:crn-‘: 1780 (y-lactone). 1755 (OAc); MS m/z (rel. int.): 302.115 [M-HOAc]+ (10) (talc. for C1,H1sO,: 302.115). 260 [302-ketene]’ (14), 165 (70). 96 (IOO),91 (46). Compound 178: lRvz:‘cm‘: 1780 (plactone), 1755 (OAc); MS m/z (rel. int.): 320.126 [M -ketene]+ (2) (talc. for C,,H,,O,: 320.126). 260 [320-HOAc]’ (7), 165 (53), 129(66), 96(100), 87(76);ClMS m/z (rel. int.): 363 [M + 11’ (5). 303 [363 -HOAc]’ (22). 207 (100). 2a,8a-Dihydroxy-la,lOa-epoxyguaia-3,ll(13)-diene-12,f%-oIide (18). Isolated as its diacetate 18a; lRvEt:‘cm-‘: 1790 (ylactone), 1750 (OAc); MS m/z (rel. int.): 302.115 [M - HOAc] + (14)(calc.forC,,H,,O,:302.115),242[302-HOAc]+(100),227 [242-Me]’ (46). 199 (66). 165 (74). 123 175). 95 (lOO),91 (68). 69 (86). 28,8a-Dihydroxy-la,lChz-epoxyguaiu-3,11( 13)-diene-12,6a-elide (19). Isolated as its diacetate 19~; IR vz$crn-‘: 1790 (ylactone), 1755(OAc); MS m/z (rel. int.): 242.094 [M - 2 x HOAc] + (14) (talc. for C,,H,,O,: 242.094), 227 [242-Me]’ (lo), 173 (36). 91 (77), 55 (100). Arteludooicinolide A (20). IR vz’!F” cm-‘: 3460 (OH), 1770 (y-lactone), 1705 (C=CC=O, C==O);MS m/z (rel. int.): 260.105

REFERENCES 1. Lee, K. H. and Geissman, T. A. (1970) Phytochemistry 9,403. 2. Geissman, T. A. and Sailoh, T. (1972) Phytochemistry 11, 1157. 3. Romo, J. and Tello, H. (1972) Rev. Lotinoam. Quim. 3. 122. 4. Romo, J., Romo de Vivar, A., Trevino, R., Joseph-Nathan, P. and Diaz, E. (1970) Phytochemistry 9, 1615. 5. Dominguez X. A. and Cardenas, E. (1975) Phytochemistry 14, 2511. 6. Ohno, B. N., Gershenzon, J., Roane, C. and Mabry, T. J. (1980) Phytochemistry 19, 103. 7. Kelsey. R. G. and Shatizadeh, F. (1979) Phylochemistry 18, 1591. 8. Alexander, K. and Epstein, W. (1975) J. Org. Chem. 40.2576. 9. Epstein, W. and Poulter, C. (1973) Phytochemislry 12, 737. 10. Jakupovic, J., Baruh, R. N., Chau-Thi, T. V., Bohlmann, F. and Msonthi, J. D. (1985) Planta Med. 51, 378. 11. Bohlmann, F., Jakupovic, J., Schuster, A., King, R. M. and Robinson, H. (1984) Planta Med. 50, 202. 12. Jakupovic, J., Schuster, A., Bohlmann, F. and Dillon, M. D. (1988) Phytochemistry 27, 1771. 13. Jakupovic, J., Klemeyer, H., Bohlmann, F. and Graven, E. H. (1988) Phytochemistry 27, 1129. 14. Abdel-Mogib, M., Jakupovic, J., Dawidar, A. M.. Metwally, M. A. and Abou-Elzahab, M. (1989) Phytochemistry 28, 3528. 15. El-Sebakhy, N. A. and El-Ghazouly, M. G. (1986) Pharmuzie 41, 298. 16. Irwin, M. A. and Geissman, T. A. (1973) Phytochemistry 12, 871. 17. Irwin, M. A. and Geissman, T. A. (1973) Phylochemislry 12, 863. 18. Yusopov, M. A., Kasymov, S. Z., Abdullaev, N. D., Sidyakin, G. P. and Yagudaev, M. R. (1977) Khim. Prir. Soedin 13,800. 19. Bohlmann, F., Knoll, K. H., Robinson, H. and King, R. M. (1980) Phytochemistry 19, 599. 20. Bohlmann, F. and Zdero, C. (1982) Phytochemistry 21,2543. 21. Jakupovic, J., Aal, M. A., Eid, F., Bohlmann, F., El-Dahmy, S. and Sar& T. (1988) Phytochemislry 27, 2219. 22. Huneck, S., Zdero, C. and Bohlmann, F. (1986) Phylochemiswy 25.883.

23. Tan, R. X., Jakupovic. J., Bohlmann, F., Jia, Z. J. and Huneck, S. (1990) Phytochemistry 29 (in press).