Coumarins from Nassauvia cumingii

~

Phytochemistry, Vol. 46, No. 8, pp. 1393-1395, 1997

Pergamon

© 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0031-9422/97 $17.00+ 0.00

PlI: S0031-9422(97)00479-2

C O U M A R I N S F R O M N A S S A UVIA C U M I N G H M. HOENEISEN,* M. SILVAand J. JAKUPOVICt Universidad de Concepci6n, Casilla 2407, Apartado 10, Concepci6n, Chile; t Institute for Organic Chemistry, Technical University of Berlin, D-10623 Berlin, Str. des 17. Juni 135, Germany

(Received in revisedform 23 April 1997) Key Word Index--Nassauvia cumingii; Asteraceae; 5-methyl coumarins.

Abstract--The aerial parts of Nassauvia cumingii gave a new phenolic compound, presumably derived from a coumarin. The complete relative configuration of a known coumarin was established. © 1997 Elsevier Science Ltd

INTRODUCTION

12'

The genus Nassauvia is placed in the subtribe Nassauviinae and is represented by 37 species distributed in the Andes from southern Bolivia to Tierra del Fuego and the Malvinas Islands [1]. In Chile, there are 24 species, l0 of which have been investigated chemically [2-8]. As many other genera of the tribe, they are characterized by the occurrence of isocedrenes and 4-hydroxy-5-methyl coumarins. Continuing with our studies of Chilean Asteraceae, we have now examined N. cumin#ii.

11'

8. l f f

9'

13'

? 0,,..

o

RESULTS AND DISCUSSION The aerial parts of N. cuminyii H. et A afforded the coumarin 1, the phenolic compound 2E and the diterpene 3. The coumarin has already been described as a constituent of Triptilion benaventei [2] and of N. diyitata [4]. The relative stereochemistry within the cyclic part and in the side-chain was correctly assigned. However, due to free rotation of the sidechain, two diastereomers are possible which would fit the spectral data. Detailed NOE investigation (Table 1) now allowed complete assignment of the relative stereochemistry. In the ~H N M R spectrum (Table 1), the proton of the hydroxyl group appeared as a doublet due to a 4j long-range coupling with the axial H4' (a consequence of the W-in the plane-orientation of the four bonds). Within the side-chain, the configuration of the epoxide ring was deduced from a NOE effect between H-6' (epoxide proton) and H-8'

1

ii I'

I

2E 2Z A6'E A6'Z

~

OI4

3

* Author to whom correspondence should be addressed. 1393

M. HOENEISENet al.

1394

Table 1. NMR data of compound 1 H

6

6 7 8 9 l'c l't 2' 4~

7.01 br d 7.32 dd 7.13 br d 2.72 br s 5.10 d 5.17 d 6.31 dd 2.10 d

4~ 6'

2.03 dd 3.13s

8'1 8~ 9' 10' 12' 13' 14' 15' OH

1.78 dt 1.50 dt 2.15 ddd(2H) 5.07 tqq 1.69 br s 1.63 br s 1.46 s 1.62 s 4.04 d

NOE

H-6'(3), H-6(10)

a-l't(1), H-2'(3), H-14'(3) H-6'(3), H-15'(3) H-9(2), H-8'~(2) H-8~(3), H-9'(1) H-10'(1.5)

OH(5),4'~(4) H-l't(5), H-2'(5), 4'~(2), 4~(5) H-l't(< 1), H-2'(2), 4~(< 1), H-6'(1.5), H-14'(5)

C

6

2 3 4 4a 5 6 7 8 8a 9 1' 2" 3" 4" 5' 6' 7' 8' 9' 10' 11' 12' 13' 14' 15'

160.4 s 106.5 s 159.9 s 114.5 s 132.6 s 127.5 d 130.9 d 114.8 d 153.9 s 24.0 q 112.3 t 143.6 d 35.1 s 42.0 t 96.8 s 66.0 d 61.4 s 38.7 t 23,7 t 122.8 d 137.0 s 25.7 q 17.7 q 26.0 q 15.3 q

J(Hz): 6,7 = 7,8 = 8; 1'c,2 = 10.5; l't,2 = 17.5; 4q,4~ = 14.5; 4~, OH = 1.5; 8q,8~ = 13.5; 8q,9 = 6.5; 8~,9 = 8; 9',10' = 7.5; 10',12 = 10',13 = 1.5.

(methylene group). The calculated conformation of two possible diastereomers l a and l b which would fit these data are depicted in Fig. 1. In the case of la, a dipolar interaction between the aromatic methyl group and the epoxide proton could be expected, while in the case of lb, an interaction between the aromatic methyl and the methyl group on the epoxide ring would be more likely. The results (Table 1) fully support the diastereomer l a with the 3 ' R * , 5 ' R * , 6 ' R * , 7 ' S * relative stereochemistry. In Table 1 are included previously unrecorded '3C N M R data. In the ~H N M R spectrum of 2 (Table 2), signals for a 1,2,3-trisubstituted aromatic compound appeared, a pattern like in 5-methyl coumarins. While a broadened signal at ~ 2.47 confirmed the presence of the aromatic methyl group, a D20-exchangeable downfield singlet at 6 10.32 indicated a phenolic aromatic hydroxyl group and, thus, excluded a coumarin. In addition, the spectrum displayed a series of signals typical of a terpenoid part. The 13C N M R spectrum indicated two keto groups but the signals for C-2-C4 of the coumarin part were missing. A total of 24 signals were observed and by assuming an intact sesquiterpene part, a nor-compound was likely. Phenolic compounds derived from coumarins by pyrone ringopening and loss of C-2 have already been obtained from members of the tribe Mutisiae [9]. The nature of the side-chain followed from the results of spindecoupling. The placement of a keto group in con-

jugation with the aromatic ring was already indicated by the chemical shift of chelated hydroxyl group, while the conjugation of the second keto group with the A6 double bond followed from the multiplicities and chemical shifts of surrounding proton and carbon signals. In accordance with their placement at C-4 and C-5', the signals for two isolated methylene groups, i.e. C-3 and C-4', were shifted downfield. The assignment of all carbon signals is based on a 2D experiment. After standing in CDC13 solution, the E-configurated A6 double bond isomerized in part to the Z-isomer. Though not a natural compound, the spectral data are included in Table 2. EXPERIMENTAL

Air-dried plant material (600 g, collected and classified by T. Stuessy and E. Ruiz in 1993 in La Parva, Chile, 2800 m, voucher deposited in herbarium C O N C no. 136786 Concepci6n, Chile) was extracted at room temp. with h e x a n e - E t O A c - M e O H (1 : 1 : 1). After removal of waxy material by treatment with M e O H at - 2 0 °, the filtrate was evapd and sepd by CC with mixts of hexane, EtOAc and MeOH of increasing polarity. Frs obtained were further purified by TLC on silica gel to give 16 mg of 1, 14 mg of 2 (TLC: CH2C12, R: 0.48) and 10 mg of 3. K n o w n compounds were identified by comparing the 400 M H z ~H N M R spectra with those of authentic material.

Coumarins from Nassauvia Cumingii

H ~

rl

H

H H

H O

H

H

H

H

H

H

H

la H

H H

H

Table 2. ~H NMR data of compounds 2E/Z and 13C NMR data of compound 2E H

2E

(A6'E)

3 6 7 8 9 l'c l't 2' 4'1 4~ 6' 8' 9' 10' 12' 13' 14' 15' OH

3.24 s 6.69 br d 7.19 dd 6.78 br d 2.47brs 4.97 d 4.96 d 6.01 dd 2.84 d 2.78 d 6.02 br s 2.10m 2.10m 5.05m 1.68brs 1.60brs 2.08 d 1.24s 10.32 br s

2Z

(A6'Z)

C

2E

(A6E)

3 4 4a 5 6 7 8 8a 9 1" 2' 3' 4' 5' 6' 7' 8' 9' 10' 11' 12' 13' 14' 15'

51.8 t 207.9 s 125.3s 132.5 s 122.9 d 132.8 d 115.7 d 159.1 s 23.0 q 111.5t 145.9d 39.5s 51.9t 200.9 s 124.6d 158.6s 41.3 t 26.1 t 123.0d 137.4s 25.6 q 17.7q 19.5q 25.5 q

H

H

H

1395

H

H

H~H

•

H

N

3.23 s 6.69 br d 7.19 dd 6.78 br d 2.47brs 4.96 d 4.95 d 6.01 dd 2.82 d 2.74 d 6.02 br s 2.54t 2.10m 5.11brt 1.66brs 1.59brs 1.83 d 1.24s 10.35 br s

H

H

lb

Fig. 1. Calculated conformations of diastereomers la and lb; the view from bottom to top of the coumarin part. In both structures the zig-zag (W)-orientation of the hydroxyl proton and the axial proton in the pyrane part, as well as the close spacial proximity of the hydroxyl group and the epoxide oxygen leading to a strong hydrogen bonding, is clearly visible. Only the structure la is in accordance with NOE results.

Compound 1. MS: m/z (rel. int.) 410.209 [M] ÷ (5) (calcd for C25H3005 410.209), 271 [M-side-chain] + (25), 228 [RDA] ÷ (100), 135 [ArCO] ÷ (55), 95 (45). Compounds 2E and 2Z. MS: m/z (rel. int.) 368.236 [M] + (45) (cald for C24H3203 368.235), 350 [M-H20] + (70), 245 [M-C9H~5] + (45), 233 [M-Ar*CO] ÷ (15), 219 [M-ArCOCH2] + (70), 203 [M-CgH~sCOCH2] + (90), 187 (70), 151 [C9H15CO] + (75), 149 [ArCOCH2] + (55), 135 [ArCO] + (100), 123 [CgHts] + (45), 69 [C5H9] + (60), *Ar = C6H3(OH)(CH3). Acknowledgements--We thank Fondecyt Project no. 1941106, D A A D and Direcci6n de Investigaci6n Pro-

J(Hz): 6,7 = 7,8 = 8; 1'c,2 = 10.5; 1%2 = 17.5; 4~,4~ = 15.5; 6',14 = 1; comp. 2Z: 8',9' = 9',10' = 7.5; ject no. 9411108-1 Universidad de Concepci6n, Chile, and Fabiola Rios for technical assistance. REFERENCES

1. Cabrera, A. L., Darwiniana, 1982, 24, 283. 2. Bittner, M., Jakupovic, J., Bohlmann, F., Grenz, M. and Silva, M., Phytochemistry, 1988, 27, 3263. 3. Zdero, C., Bohlmann, F., King, R. M. and Robinson, H., Phytochemistry, 1986, 25, 2873. 4. Pritschow, P., Jakupovic, J., Bohlmann, F., Bittner, M. and Niemeyer, H. M., Phytochemistry, 1991, 30, 893. 5. Bittner, M., Jakupovic, J., Bohlmann, F. and Silva, M., Phytochemistry, 1989, 28, 2867. 6. Bittner, M., Silva, M., Rozas, Z., Papastergiou, F. and Jakupovic, J., Phytochemistry, 1994, 36, 695. 7. Bittner, M., Jakupovic, J., Bohlmann, F. and Silva, M., Phytochemistry, 1988, 27, 3845. 8. Zdero, C. and Bohlmann, F., Plant Systematics and Evolution, 1990, 171, 1. 9. Zdero, C., Bohlmann, F., King, R. M. and Robinson, H., Phytochemistry, 1986, 25, 509.