Sesquiterpene lactones from Artemisia rutifolia

Sesquiterpene lactones from Artemisia rutifolia

Short Reports 1714 for 1 hr. Usual work-up afforded a mixt. of corresponding hydroxy and mcthoxy compounds (1: obtained compounds were identical ...

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Short Reports

1714

for 1 hr. Usual work-up

afforded a mixt. of corresponding

hydroxy and mcthoxy compounds (1: obtained compounds were identical

pteropoda

12x-Methoxy-9.11 for

‘:

cm

-dehydro-ent-kaur-

C2,H3,,0J:

[M-HOMe]’

compound

9

reported

330.219).

16-en- 19-oic acid (8). Oil;

int.): 330

315

[Ml’

(100) (talc. for

[M-Me]’

(12). 283 [298-Me]’

(28).

1. Janzen, D. H. and Liesner, R. (1980) Brenesia 18, 15. 2. Wiemer, D. F. and Ales. D. C. (1981) J. Org. Chem. 46, 5460. 3. Khan,

[N].

1695; MS m/z (rel.

REFERENCES

12-

TLC separation we

8 and 9. Our spectral data of compound

to those of the 12-hydroxy

from Montanoa IR v:t:

I). On

298

(12).

M. A., Gray,

Lbnoum. 4. Pioui,

A. 1. and Waterman,

P. S. (1989) Ret;.

Qu~m. 20, 75. F., Passannanti,

5. Hanrick,

S., Paternostro,

10,

(197 1) Phyrochemistry

M. P. and Sprio, V.

1164.

C. A. and Jefiries, P. R. (1964) Auslr. J. Chem. 17,

915. 6. Bohlmann, 7. Brieskorn,

F. and Le Van, N. (1977) Phytochemistry 16, 579. C. H. and Poehlmann,

E. (1969) Chrm. Ber. 102,

2621. 8. Bohlmann, Acknowledgemmt-Foundation

M.A.

thanks the Alexander

F. and Le Van, N. (1978) Phyrochemistry 17, 1957.

9. Ortega, A.. Morales,

van Humboldt

F. J. and Salmon, M. (1985) Phycochem-

isfry 24. 1850.

for a fellowship.

Phyrochemisrry,Vol. 30. No. 5. pp. 1714-1716.1991 Printed in Great Brnam

SESQUITERPENE J.

University,

Lanzhou

730000,

LACTONES

JAKUPOVIC.

Institute for Organic Chemistry.

f;

Technical

R. X. TAN, University

P.R. China; tlnstitute

FROM

F. BOIILMANN;, of Berlin, D-1000 Halle!Saalc,

(Received

Abstract-The hydroxycostic

Arremrsla

rurrfolra;

polar fractions of Artemisia acid methyl ester. Structures

Z. J. JIA*

Compositae;

and S.

Berlin 12, Germany;

of Plant Biochemistry,

4020

Key Word Indexesmane derivative.

ARTEMZSIA

Academy of

0031~9422/91 $3.00+0.ccl 1991Pergamon Press plc

RUTZFOLZA HuNEcKt l

Department

Science

of Chemistry.

of the G.D.R.,

Weinberg

1990)

sesquiterpene

lactones; guaianolides;

germacranolide;

rutifoliu afforded three new guaianolides, a germacranolide were elucidated by high field NMR techniques.

INTRODUCTION

RESULTS AND DISCUSSION

In addition to compounds isolated previously [ 11, we isolated the guaianolides 1-3, the germacranolide 4 and the eudesmane derivative 5 from the polar column chromatography fractions. The ‘HNMR spectrum of 1 (Table 1) indicated the presence of a guaianolide with a 2,3-double bond by a pair of doublets at 65.61 and 5.94. As these protons showed no further vicinal couplings, C-l and C-4 are

G.D.R.-

Germany

3 Augusr

In our previous study of Artemisia rutiJolia Steph. ex Spreng [I], we obtained from this plant a very polar mixture of lactones, the structures of which were not elucidated. We have re-investigated this fraction from plant material collected in Bulgan-Aimack in Mongolia.

Lanzhou

eud-

and a tri-

quarternary. All data agreed with the proposed structure. The stereochemistry was determined by NOED. Clear effects were observed between H-6 and H-15 (5%) but not between H-6 and OH-l, between H-7 and H-S (6%) as well as between H-l 5, H-6 (10%) and H-3 (6%). The ‘H NMR spectrum of 2 (Table 1) was similar to that of I. However, the exomethylene proton signals were replaced by a singlet at 6 1.45 indicating a IO-hydroxyguaianolide. The configuration at C-IO was proposed by comparison with the spectra of similar guaianolides and from biogenetic considerations as several IOz-hydroxyguaianolides were isolated from this species [I]. The ‘H NMR spectra of 3 and its acetate 3a (Table I) showed that a guaianolide was again present. Spin decoupling indicated a 12,6x-olide with oxygen functions at C-2, C-5 and C-10. Comparison of the chemical shifts of 3 and 3a with those of related lactones led to the assignment of the configurations at the chiral centres. The

Short Reports

Table

I. ‘H NMR spectral

H

1

data of compounds

2

5.61 d

3 5 6 7 13 13’ 14 14

5.94 2.42 4.12 3.29 6.25 5.56 4.96 4.75

I5

1.34s

OMe OAc

d d dd ddddd d d br s br s

l-3, 3% 4 and Sa (400 MHz, CDCI,,

3

3a

4+

2.16d

2.28 d

2.92 d

5.79 d

4.85 br s

5.83 ddq

3.97 ddq

5.93 d 2.17 d 4.67 t 3.15 ddddd 6.15d 5.47 d

5.68 dq

5.67 dq

6.40 dq

4.35 3.39 6.21 5.50

4.54 3.38 6.20 5.50

5.26 2.78 6.21 5.69

1.45 s

1.53 s

1.24s

1.91 s

1

2

1715

d In d d

-

1.34s

d m d d

d ddddd d d

a-values) sa 4.79 dd 1.644 2.24 m 5.17 br 2.02 br 5.56 t 2.48 br 6.17 br 5.66 br

dd d ddd s s

1.41 s 1.90s

5.00 br s 4.73 br s 3.78 s 1.87 s 2.04 s 2.10s

*H-8 2.18 and 1.71 m; H-9 2.06 ddd and 1.83 m. J Hz: Compounds 1 and 2: 2,3 = 5.5; 5,6= 11; 6,7 =9; 7.8 = 10; 7,8’= 3.5; 7,13 = 3.5; 7,13’= 3; (compound 2: 5,6=6,7=9.5); compounds 3 and 30: 1,2=4.5; 2,3=2; 2,15=1.5; 3,15=1.5; 6,7=10; 7,13=3.5;7,13’=3;compound4: 1,2=2.5;2,3=4;2,15=3,15=1.5;6,7=2;7,8=5;7,8’-8;7,13=1.5; 7,13’=1.3; 8,9=2; 8’,9=7.5; 9,9’=15; compound * 1.2x=4.5; 1,2/I=2a,Zr!I=2~,3=12; 2q3=5; 5.6 =6.7=10; 7,8=4; 7,8’=10.

olide by aflylic oxidation and rearrangement. Further oxidation leads to the S-keto-1,2epoxide. The structure and the configuration at all chiral centres of 51 followed directly from its ‘H NMR spectrum (Table I) as spin decoupling allowed the assignment of all signals. The resulting sequence and the observed coupling agreed only with the proposed structure. EXPERIMENTAL

1’

4

0

5 R=H 5a R=Ac

observed shift differences of H-6 and H-14 on acetylation of 3 agreed with the proposed stereochemistry. The ‘HNMR spectrum of 4 (Table 1) indicated the presence of a germacranolide. Spin decoupling led to two sequences. The downfield shifts of H-2, H-3 and H-6 required a keto group at C-5, while the shifts of H-l and H-2 indicated the presence of an 1,2-epoxide with a lOhydroxy group. NOED allowed the assignment of the stereochemistry by effects of H-14 with H-l (6%) and with H-8 (4%), H-15 with H-3 (8%). H-7 with H-l (So/,), H-2 with H-6 (10%) and H-l with H-7 (6%) and H-14 (3%). Lactone 4 is probably formed biogenetically from costun-

The air-dried aerial parts (800 g, collected in June 1988 in Bulgan-Aimak, Mongolia, voucher MVR 88) were extracted and the extract worked-up as reported previously [l, 23. The two most polar CC fractions (I&O-MeOH, 4: 1) were separated by HPLC (MeOH-HzO, 1: 1. always RP 8, flow rate 3 ml min-I). The first gave 5 mg 3 and a mixture which gave after acetylation (AczO-pyridine, room temp.) and TLC (EtzOCHzCl,, I : 5, x 2) 4 mg So (R, 0.39). The second fr. gave 3 crude frs (2/l-2/3). TLC of 2/l (CHzCIz-MeOH, 14: 1, x 2) gave 2 mg 4 (R, O.Sl), fr. 2/2/ 3 mg 1 (TLC: CHzClz-h&OH, 14: 1, x 3, R, 0.63) and fr. 2/3 2 mg 2 (TLC CHzCIz-MeOH, 9: I, x 2, R, 0.34). 1z,4a-Dihydroxygunia-2,10(14),11(13)-trien-12,6a-&de (1). IR v2,“F’ cm - 1: 3600 (OH), 1770 (y-lactone); MS m/z (rel. int.): 262 [Ml’ (1). 247 [M-Me]’ (28). 244.109 [M - HzO] + (9)(calc. for CrsH,,O,: 244.1093. 229 [244-Me]’ (6). 98 (100), 81 (36), 69 (38), 55 (54). 1x&,10x- Trihydroxyguaia-2,11( 13)-dien- 12.6~~elide (2). IR cuci, cm- 1. 3600 (OH), 1770 (y-lactone); MS m/z (tel. int.): 280 v,, [M]+ (3) (d 1s H 200 5.) 145 (74). 127 (100). 2jI,5a,lO~-Trihydroxyguaia-3,11(13)-dien-12,6a-olide (3). MS m/z (rel. int.): 262.121 [M-H,O]+ (38) (talc. for C,3H,,0,: 262.121), 247 [262 - Me] + (26). 244 [262 - HzO] + (26), 229 1244 -Me]+ (30). 95 (LOO), 69 (86). Acetylation of 3 gave 3a, IR

1716

,c;

Short Reports

cm

-

‘1

3600 (OH), 1790 (y-lactone), 1750 (OAc); MS m/z (rel.

int.): 262.121

[M-HOAc]-

244 [262-H,O]+

(8) (talc. for CITH1s04:

- HOAc]

+ (21). 303 [363 - HOAc]

(100); EIMS

262.121),

- kctene]’

(4). 162 (31). 91 (57), 59 (lOO), 55 (66).

I /1.2z-epo.~J’germucra-3Z, I I ( 13)-dien12,62-&de (4). I R v~~,‘lf”cm _ ’ : 3600 (OH). 1770 (i’-lactone); 1700 (C=CC=O): MS rn/- 278 LMJ - (2). 167 (14). 12X (78). 83 (54). 69 (52). 55 (100).

+ (26). 243 [303 - HOAc]

m/z (rel. int.): 302 [M - 2 x HOAc]

+

* (2). 260 [302

(26). 242 [302 - HOAC] ’ (22). 183 (100). 133 (73).

IO/~-ff~dr~,.\-)-5-oro-

REFERENCES 1. Huneck,

triacetate

5~; IR

ClMSm.::frel.

vE?crn

ml.):423

‘: 1755

[M+

I].

(OAc),

(C=CCO,R);

1725

(12)(C,,H,00,+

S., Zdero. C. and Bohlmann.

Phptochemistrp

23. 1979.

0031-9422191$3.00+0.00 i” 1991 PergamonPressplc u,

Phyfochumistry, Vol. 30. No. 5, pp. 1716 1719. 1991

EREMOPHILANOLIDES DELGADo,t

lnshtuto de Quimica de la Univcrsldad MCxico, D.F.: ZDcpartamento Estado de Morclos. Avenida

National

Universidad

National

FROM ROLDANA

PATRICIA E. GARCiA,$

de Quimica Au16noma

(1986) Phyrochem-

2. Bohlmann, F., Zdero. C.. King, R. M. and Robinson. H. (1984)

I). 363 [423

Pnnted in Great Britain

GUILLERMO

F.

isrr): 25, 883.

l/I.3/~,631-~rrlh~dro,~y~osfrc acid methyl esrer (5). Isolated as its

Autbnoma

Orginica

SESSILIFOLIA”

ROBERT A. BYE$ and EDELMIRA LINARES~

de MCxico, Circuit0

Exterior, Ciudad

Universitaria,

de la Facultad de Ciencias Quimicas e Industriales,

1001. Cuernavaca, de Mexico.

Morelos, Mexico; $Jardin Botinico.

Apdo

Postal 70-614, Coyoacin

04510,

Coyoacin

Umversidad

04510,

Autbnoma

del

Instltuto de Biologia. Universidad Mkxico,

D.F.

(Receiord 31 July 1990) Key Word

Index

determination:

-Ro/dana

sessi/$olia;

Compositae;

roots; medicinal

plant; sesquiterpene

lactones; structural

bioassay.

Abstract-Chemical investigation of the roots of the medicinal plant Roldanu sossilifolia yielded Iz-angeloyloxylO/Ill-crcmophil-7( 1l)-en&.12-elide, 1x-angeloyloxy-10/I-hydroxy-eremophil-7( 1l)-en-8x,12-olide and lz-angeloyloxy-lOPH,8/1-hydroxy-eremophil-7( 1I)-en-8r,l2-olide. The first two are new compounds and their structures elucidated by spectroscopic and chemical methods. The compounds were not toxic in an Artemiu w/ha bioassay.

INTRODUCTION

Roldanu

sessilijblia

(Hook. & Am.) H. Robins. & Brett. is a member of the ‘cachana’ medicinal plant complex [l] and grows in the pine-oak forests of southern Sierra Madre Occidental, western and central Transvolcanic Mountains and adjacent Sierra Madre Oriental of Mexico. The roots of ‘cachana’, ‘cachane’ or ‘cachani’, along with other plants are used in preparing a tea to treat female sterility [2]. Also known as ‘raiz de peyote’, it is the basis of a tincture that is rubbed onto the body to alleviate rheumatic pain. It is found in markets and herb shops throughout Mexico and is imported into the United States. In continuation of our studies on Mexican plants [3], we report the isolation and structural elucidation of lr-angeloyloxylOflH-eremophil-7( 1 l)-en-8a,12-

*Contribution

1017 from

the Institute

de Quimica

Mtxico. ‘rAuthor to whom correspondence should be addressed.

Universidad

National

Autbnoma

de

de la

olide (I), Iz-angeloyloxy-IO/I-hydroxy-eremophil-7(1 en-8x,12-olide (2) and la-angeloyloxy-lOpH,8,0-hydroxyeremophil-7(l l)en-8a,I 2-olide (3).

l)-

RFSUITS AND DISCUSSION The n-hexane extract from the dried roots of the plant was subjected to column chromatography over silica gel to yield compounds l--3 which proved to be eremophilanolides. Compound I, mp 125-128’, analysed for CZ0H2s04. The UV (&,., 215 nm. ~23 100) and IR (Y,,, 1745, 1707 and 1690 cm - ‘) data indicated the presence of an x$unsaturated-y-lactone and an unsaturated ester. The ‘H NMR (Table 1) and “C NMR (Table 2) spectra were consistent with the presence of a tertiary methyl, a secondary methyl, an olefinic methyl and an angeloyl residue, establishing that the lactone belongs to a sesquiterpene of the eremophilane-type. The cis-decaline structure of 1 was established by the chemical shift of the C-S methyl protons (6 1.12 in