Daucanes and other constituents from Ferula sinaica

Phyro~~hemislry, Vol. 30, No 4, pp. 1207 1210,1991 Printed in Great Britain.

DAUCANES

003l-942291 $3.00+0.00 Q 1991Pergamon Press plc

AND OTHER CONSTITUENTS

FROM FERULA

SZNAZCA

AHMED A. AHMED+ Institute for Organic Chemistry, Technical University of Berlin, D-1000 Berlin 12, F.R.G. (Recriued in reoisedjorm 10 May 1990)

Key Word Index --Fendo sin&a; Umbelliferae; sesquiterpenes; daucane esters; monoterpenes; bornane.

Abstract-A new anethol

reinvestigation of the roots of the Ferula sinaica afforded seven new daucanes, derivative. The structures were elucidated by high field NMR techniques.

INTRODUCTION

The chemistry of the genus Ferula has been studied by many groups. The widespread compounds in this genus are characteristics daucanes, humulanes, himachalanes as well as guaianes. Only, a few monoterpenes have been detected Cl]. Recently, we reported from F. sinaica nine daucanes, of which three were new, in addition to three sesquiterpene coumarins [2]. A new sesquiterpene coumarin, two daucanes and a propiophenone were reported from a Saudi Arabian collection [3]. We have now studied some further fractions and the results are discussed in this paper. RESULTS AND DISCUSSION

The methylene chloride extract of the dried roots of afforded seven new daucanes, 3, S-8,10 and 11, a new monoterpene (13) as well as a new t-cinnamylalcohol derivative (14), in addition to ferugin (2) [4], lancerodiol p-hydroxybenzoate (9) [6], 8-hydroxyborneol (12) [7] and santoline [8]. The ‘H NMR data of 2 and 3 were compared with those of the closely related compound 1, which has been reported from the same species [2]. The presence of two proton doublets at 67.82 and 6.78 in the ‘HNMR spectrum of 2 and at 67.95 and 6.88 in the spectrum of 3, indicated the presence of a p-hydroxybenzoyl group. This was clear from the mass spectrum which gave a peak at m/z 236 [M - p-hydroxyb-enzoic acid] + . The downfield shift of H-6 of both compounds 2 and 3 showed that the phydroxybenzoyl group must be at C-6. In the ‘H NMR spectrum of 2, H-9 appeared as a double doublet at 64.15 which was typical for lancerotriol with hydroxyl group of r-configuration [4]. The presence of H-9 in 3 as a broad signal at 64.50 confirmed a different stereochemistry of this hydroxy group. Thus 3 was the previously unreported epimeric compound of 2. The structure of 5 was deduced from the ‘HNMR spectrum (Table 1) which was of course very similar to that of the isomeric compound 4, previously reported from the same species [2]. This was clear from the F. sinaica

*Permanent address: Department of Chemistry, Faculty of Science, El-Minia University, El-Minia, Egypt.

a new bornane

as well as a

chemical shifts of H-6 and H-9, which were present at 65.54 and 3.66, respectively for 4 and at 64.12 and 5.01, respectively, for 5. All other signals were identical, the stereochemistry of 4 has been confirmed by synthetic methods. Furthermore, the “CNMR data (Table 2) agreed with the proposed structure. The ‘H NMR data of 6 and 7 were very close, in addition, 7 exhibited four aromatic protons as two doublets at 6 7.92 and 6.90, characteristic for p-hydroxybenzoyl group. This was clear from the mass spectrum which contained two peaks at m/z 121 and 138 as well as 13C signals at S 131.90 and 115.50(Table 3). Spin decoupling experiments with 7 allowed the assignment of all signals. The olefinic proton which appeared as a broad singlet at 66.03 showed only a long-range coupling with the olefmic methyl at 62.02. The downfield shift of both signals indicated a neighbouring keto group. The z,fl unsaturated ring carbonyl group was confirmed by IR (1650 cm-‘) and 13CNMR (6209.70). Furthermore, spin decoupling starting from the well known proton H-5, allowed those of H-6 and H-7 to be assigned. The phydroxybenzoyl group was located at C-6 according to the chemical shift of H-6. Methanolysis of 7 gave a compound of which *H NMR, MS and IR were identical with 6. The mass spectrum of 8 was in agreement with the molecular formula C,,H,,O, (m/z 432). Some important fragment ions were observed at m/r 332 and 232 due to the elimination of one and two angelic acid molecules respectively. The presence of the angelates were clear from the ‘H NMR spectrum (Table 3). The similarity of 8 with 6 and 7 was obvious from the chemical shifts and coupling constant of H-5, H-6, H-7 and H-9. Additionally, a proton geminal to an ester group was observed at 64.94, which coupled to methylene protons giving signals at 6 2.53 and 1.62. This proton was assigned as H-2 geminal to an angeloyl group. While the second angelate was placed at the usual C-6 position on the basis of the downfield shift of H-6 at 65.79. The coupling constants of H-2 (9 and 10 Hz) were typical for the a-configuration of this proton [9]. The stereochemistry of the asymmetric centres of 6, 7 and 8 were established by comparison of the chemical shifts as well as the coupling constant with those of a compound recently reported from F. tingitana c51.

1207

1208

A. A. AHMED

i

R =

H,aOH

2

R =

p - Hydroxybentoate.

3

R =

p- Hydroxybenzoate. BOH

7

R’ = p-Hydroxybenzoate,

8

R’ =

40H

R’ = H

R’ = Angeloyloxy

4

K’ =

p -Hydroxybenzoate,

5

R’ =

H, R” = p -Hydroxybenzoare

9

R=H

10

R =

R2 = H

OH

HO

Table 1. ‘H NMR spectral data 013 and 5 (400 MHt CDCI,. &values)

5 6 7’ 9 10

10 II I2 13

f&e

14

14

The structure of 10 followed from the ‘H NMR spectrum which was very close to that of 9 [6]. The presence of an additional oxygen function at C-2 was determined by spin decoupling. Irradiation of the doublet at 63.44 collapsed the signals at 62.27 and 1.54, which were assigned to H-3. A pair of doublets were present at d2.76 and 2.40, which required a neighbouring keto group.

15 3’.7. 4’,6

2.04 5.58

3.14 2.31 4.50 hrs 2.03+ i.75* I .62 0.x3 0.86 i 5.07 5.21 hr hrss 1.33 7.95 6.X8

2.38 d 4 ttli&i 2.65 dd I.XX dd S.01 dd t .94 dd I.85 dd 2.02 In 0.87 d 0.91 d 1.17 s 1.09 s 7.82 d 6.80 d

*JLHz]: 9,10=3; 9.10’=5: ~&lo’= 15. .I [Hz]: Compound 3: 5.6 = 10; 6-7 = 6.7’ =5; 9.10=6; 9.10’- Iz: 10.10’= 14.5; 11.12 =11,13=6.5; compound 5: 5,6=tO; 6.7=2: 6,7’=6: 7.7’= 16; 9.10=9.10’=4; 10.10’=15; 11.12-11.13-6.5.

Daucanes

and other constituents

Table 2. 13CNMR spectral data of 5 and 7 67.9 MHz, CDCI,) C

2 3 4 5 6 7 8 9 10 11 12 13 14 15 2 Y.7’ 4’,6 5’

The mass spectrum of 11 showed loss of a water molecule, an isopropyl radical and anisic acid at m/z 370, 345 and 236, respectively. Its IR spectrum exhibited absorptions of an hydroxyl group at 3660 cm- ’ and an ester carbonyl function at 1720 cm- ‘. The ‘HNMR data indicated the presence of one methyl group linked to a quaternary carbon atom at 6 1.05, two isopropyl doublets at 60.92 and 0.83 and a panisoyl ester group at 67.96.6.93 and 3.87. In addition an olefinic methyl, an olefinic proton as well as a proton geminal to a hydroxyl group were present (Table 3). Using the spin decoupling technique the structure of 11 could be determined, again starting from H-5 the signals of H-6 and H-7 were detected. The olefinic proton showed a coupling with two double doublets at 62.21 and 1.87, leading to the sequence C-8X-9-C-10. The additional hydroxyl function is placed at C-2. Comparison of the chemical shifts and coupling constant of 11 with compounds reported from F. communis var. hreuifolia and F. jaeschkeana [ 10, 1 l] confirmed the stereochemistry. The ‘HNMR spectrum of 13 suggested a bornane derivative. Three methyl groups appeared as sharp singlets at 6 1.06,0.85 and 0.81. Also two protons geminal to hydroxyl groups at 63.84 and 3.83 were observed. Spin decoupling located the two protons at C-2 and C-5. On the basis of the coupling constant and comparison with the bornane derivatives which were reported in the literature [7, 12, 133 the configuration at C-2 and C-5 could be established. The mass and IR spectra supported the proposed structure (Experimental). Thus 12 is a 2a,5/3_dihydroxybornane. The spectral data of 14 (Experimental) showed that an anethole derivative was present [l4, 151. The presence of narrow meta-coupled doublets at 66.66 (J = 2.5 Hz) and 6.51 (5=2.5 Hz) supported the asymmetric disubstitution at C-3 and C-5. Furthermore, H-7 appeared as a

7

5

55.7 31.2 38.4 84.8 50.4 70.5 38.9

s I I s

42.5 31.3 42.2 86.3 56.4 68.0 42.2 75.9 78.5

s r t s d d t s d

151.2 s 128.5 d

42.9

1

209.7 s

d

d t

31.8d

37.5 d

18.3 qb 18.1 qb 28.3 q 17.3 q

17.1 4’ 18.4 q’ 30.2 y 21.5 4 166.5 s 121.0 s 131.5 d

166.6 s 121.5 s 131.9d

115.0d 161.25

115.5d 161.4 s

1209

from Ferulo sinaica

‘.“Interchangeable.

Moreover, spin decoupling allowed location of H-5, H-6 and H-7 at 62.41, 6.07 and 6.13, respectively. The presence of the p-hydroxybenzoyl group indicated by the two doublets at 67.85 and 6.81. This agreed with the mass spectrum, a molecular ion at m/z 250 [M - p-hydroxybenzoic acid] +, 138 Ip-hydroxybenzoic acid]‘, 121 [phydroxybenzoyl acylium] + .

Table 3. ‘H NMR spectral data of compounds 611 (400 MHz, CDCI,. &values) H

6

2 3 3 5 6 7 7 9 IO

-

1CY 11 12 13 14 15 3’,7’ 4.6

7

2.15 4.46 2.78 ddd 2.42 ddd 5.89 -

2.57 5.84 3.03 ddd 2.47 ddd 6.03 -

I .76 0.89 0.96 1.97 1.32 -

1.63 0.85 0.87 2.02 1.40 7.92 6.90

-

lOAng: 6.18 qq. 6.08 qq. 2.03

8*

10

4.94 2.53 1.62 2.53 5.79 2.97 ddd 2.38 ddd 5.96

3.44 2.27 1.54 2.41 6.07 br

1.52 0.90 0.91 1.99 1.46

6.13 brs

11

d

3.49

dd

2.30

dd

1.51 dd 1.99d 5.36 ddd 2.51 brdd 2.30

ddd

-

5.57

br s

2.76 d 2.40 1.73 0.78 0.87 1.82 1.07 7.85 6.81

2.21

dd 1.87 d 1.81 m 0.83 d 0.92

d

1.82 brs 1.05 s 7.96 d 6.93

d

dq, 1.98 dq, 1.88 dq. ti 2,3 = 9; 2.3’ = 10, 3.3’ = 14; 5.6 = 1% 6,7’ = 5; 6,7 = 3; 7.7 =17;9,7=9,7’=1;11,12=11,13=6.5;compound10:~3=9;2,3’=10;3,3’=1S;5,6 = 10; lO,l(Y= 15; compound 11: 2,3=9; 2,3’= 19 3,3’= 15; 5,6= 10; 6,7=3; 6.7 =lo; 7,7’=14;9,10=8; 10.10’=15; 11,12=11,13=6.5. J [Hz]: Compounds

A. A. AHME~

double doublet at 86.50, H-8 as a double triplet at 66.27, H-9 as a double doublet at 64.31, two methoxyl groups were observed at 63.89 and 3.87. The mass and IR spectral data agreed with the proposed structure, EXPERIMENTAL The air-dried roots of F. sirwica Bioss (2 kg, collected from the North Sinai pcnmsula. in March 1987) were extracted and separated as reported previously [Z]. The compounds isolated werc:20mg2.3mg3,30mg5,2mg6,100mg7,4mg8,15mg9, 6 mg 10.9 mg 11.5 mg I2 and 2 mg 13. The known compounds were identified by comparrson of thetr ‘H NMR, mass and IR spctra with those which have been reported In the literature. 4lI,YV-Dih~drox4’-6r-p-hyJ’“.u~henzo?,ln.u~darrc-8( 14)~ene (3) or 9-epi-6-p-h~tdro.u~hun,tn:list,lun~,rrnlrioI 3. [s ]F + 2 1.9 _ 3460. 1750, 1620; MS m;z (McOH; (*0.57); IRYL~,‘,“ cm ‘.. _ U‘W, (Tel. mt.): 331 [M -431’ (4). 313 [331 -. IK]+ (C).6), 236 [M -.- l38]* (71, 13X[p-hydroxybcnzoic acid] ’ (3), 121 [phydroxybenzoylacylium]

+

The author thanks the Alcxandcr van Humboldt Stiftung for the fellowship supportmg this work and Prof. Dr F. Bohlmann (TU Berlin, I’.R.G.) for the opportumty to Ackncwledgements

work in his group.

I l(Hl).

4/L6cr,8/C Trilrydro.u~-91-p-htdr~x~~~~z~~~~~~_~~du~~~ne

(5).

c 0.48); IR \I;I;% cm’ I: 3650. 3610. 3450, 1710, 1650: CIMS m,:; (ml. mt.): 393 [M + I J’ (20). 375 LM -IS]’ (38) 357 [M-336]’ (541, 219 [357 1381’ (100). 4P,63_L)ih~drclx~dul(c.-8_L’ne- IO-onr (6). I R \t~~~‘~cm - 1: 3520, 3480, 1640; MS m!; (rel. int.): 252 [M] - (4). 234 LM- 181’ (61, 209 [M-43]+ (75). 191 [234-43]+ (38). (7). 6~x-p-H~dm.u)lbun=~)~,~(~.~~-4~-~~~r~).~.~~~u~.-~-~~~1O-one [r]$ + 12.9 (CHCI,; ~~1.12); Irving”) cm-“: 3610, 1780, 1650; CIMS m!z (rel. int.): 373 [M]’ (I), 329 LM -431’ (38), 235 [M - 1381 * (41). I38 [benzoic acid] ’ (20), 121 [bcnzoate] * (55). 84 (100). M4thunolysi.s ($7. Compound 7 was treated with 3”/0 KOH m MeOH for 3 hr. The mrxt. was diluted with water and extracted with CH,Cl, to g~vc 6. 2/~.6x-~ianyulo pfo.x ~-4(j-h~droxpdauc-8-cne1O-ene (8). IR ;;;‘I I om ‘:;hK(;. 1700. 1610; MS m ,Iz (rel. ink): 432 [M] ’ (O-2), ;89 [M -43.1 ’ (O.?), 332 [M -- l(X)] - (O.S), 232 1332 -.. loO]+ (15). 83 (100). 2P-Hydrox~-6-p-h~dr~~~~b~n~o~llun~,erf)dl[~l (IO). IR Y~~~‘~cm - I. 3620, 3580, 3490, 163; MS m?z (rcl. int.): 250 [M - 13&l+ (3 1), 232 [250 -- 181’ (39) 207 [ 250 - 431 ’ (30), 138 [phydroxybcnzoic acid] + (22). 12 1 [p-hydroxybenzoyl acyhum J + (loo). [z&4

2a.56c-Dihydroxyhornone (13). IR Y$~~‘~cm - I : 3610; MS m/z (rel. mt.): 170 CM]’ (0.6), 155 [M- 151’ (5.5), 137 LM- 15 -- 183’ (20), 111 (100). ‘HNMR(J00MHz.CDCI,):fi3.84(1H, ddd, J = 1.5, 3.5 and 10 Hz. H-2), 3.83 (I H, dd, J = 4 and 8 Hz, H5), 2.30 ( 1H, dd, J = 8 and 14 Hz, H-6), 2.23 I 1H, ddd. J = 5.10 and 14 Hz, H-3). I.67 (1Hf.d. J-5 Hz. H-4). 1.34(lH. ddd, J- 1.5. 4 and 14 Hz, H-6), I.06 (s, H-7), 0.84 (.I’.H-9). 81 (s, H-IO), 0.75 (I H, dd, J - 3.5 and 14 Hz. H-31. u/who1 (14). IR 3.4-L)imethr~x~-5-h):dr~~~~-t-rrnnum~l YLl$l’ cm - 1: 3360, 1560; MS m;; (ret. int.): 210 (100); ‘H NMR (400 MHz. CDCI,): (56.66 (1 H, d, J=?.5 Hz, H-2), 6.51 (IH. d. J = 2.5 Hz, H-6). 6.50 (1H. dt. J = I and 16 Hz, H-7), 6.27 (IH. dl, J-6 and 16 Hz, H-8). 4.31 (2H, dd, J = I and 6 Hz, H-9). 3.89 (3H. s, OMc). 3.87 (3H. s. OMc).

REFERENCES

- 15 4 (McOH;

2ll-Hl’dr~).\-).-6-p-h~dr~).~~.~)~n~f~~.~-/~~.~~h~eu~~di~~~ (1I 1. [r]i4 + 14 (CHCI,; c1.75); IRvkt:“l cm _‘: 3660. 3610. 1720; MS rn:; (rcl. int.): 370 [‘M - 18]+ (0.2).345 [M -433’ (6), 236 [M - 152]+

(3). 84 t1oQ.

1. 3 I. 3. 4 5. 6. 7. 8. 9. IO.

1I. I2 13. 14 I5

Garg, S. N. and Agarwal, S. K. ( 1988) Phytochemistry 27,936. Ahmed, A. A. (1990) J. :Yur. Pro&. 53, 483. Al-Hazimi. H. M. G. (19#6) Yhytochemistry 25, 2417. Garg, S. N.. Agarwal, S. K., Mahajan. V. P. and Rastogi, S. N. (1987) J. Nut. Prod. 50. 253. Miski, M.. Ulubelen. A.. Mabry, T. J.. Watson, W, H., Vlckovic, I. and Holub, M. (1984) T