Isocedrene derivatives and other constituents from Acourtia nana

Phytochemistry, Vol. 30, No. 8, pp. 2695-2697,1991 Printed in Great Britain.

ISOCEDRENE

0031-9422/91 $3.00+0.00 Q 1991Pergamon Press plc

DERIVATIVES AND OTHER CONSTITUENTS ACOURTIA NANA

C. ZDERO,

F. BOHLMANN,

and X. A.

H. SANCHEZ*

FROM

D~MINGUEZ*

Institute for Organic Chemistry, Technical University of Berlin, D-1000 Berlin 12, Germany; *Institute Tecnologico y de Studios Superiores de Monterrey, Sucursal de Correos “.I”, Monterrey, N.L., Mexico (Received 1 January 1991)

Key Word Index-Acourtia nana; Compositae; sesquiterpenes; isocedrene derivatives, phenol&; perezone; c(- and /%pipitzol.

Abstract-The aerial parts of Acourtia nana afforded five new isocedrene derivatives and two aromatics related to the Smethylcoumarins common in the subtribe Nassauviinae. Perezone and the isomeric pipitzols were isolated from the roots. The structures were elucidated by high field NMR techniques. Chemotaxonomic aspects are discussed briefly.

INTRODUCTION

The genus Perezia with about 30 species is mainly dis-

tributed over Southern America in the Andes region. The genus has been separated from Acourtia [l], previously a section of Perez@ mainly present in central and the southern parts of North America. Chemically these two genera differ by the occurrence of isocedrenes in the genus Perezia [24] and perezone and related compounds in the species placed in the genus Acourtia [S-S]. We have now studied the chemistry of Acourtia nana (A. Gray) Reveal et King.

the ester groups. The 13C NMR spectrum (Experimental) also agrees with the structure. The ‘H NMR spectrum of 2 (Table 1) showed that we were dealing with the corresponding angelate as followed from the replacement of the epoxyangelate signals by those of an angelate. All other signals were nearly identical.

RESULTS AND DISCUSSION

The aerial parts of A. nana gave taraxasteryl and lupeyl acetate, the isocedrene derivatives l-5 and the aromatic compounds 6 and 7. ‘HNMR spectrum of 1 (Table 1) showed similarities to that of similar compounds with an ester group at C-3 and acetoxy groups at C-14 and C-15 [9]. Accordingly, low field signals at 66.75 (t, H-15) 5.96 (Ca,H-14), 5.88 (ddd, H-3) and 5.31 (q, H-4) were visible. Typical signals showed that in addition to two acetoxy groups, an epoxyangelate was present. A further signal at 64.03 (br s) indicated an additional oxygen function. The mass spectrum showed that this was probably a hydroxy group, as the highest fragment (m/z) 404) corresponds to CZ2H2s07, formed by loss of acetic acid. Spin decoupling allowed the assignment of all signals, only those for H-2 and H-7 being overlapped in deuteriochloroform. In deuteriobenzene these signals also appeared as clear double doublets. The low field signal at 64.03 showed a small W-coupling with H-10. Inspection of a model indicated that this required a la-hydroxy group. This, and the whole stereochemistry, was further supported by the observed NOES [H-13 with H-9j (7%) and H-2 (7%), H-12 with H-10 (lo%), H-5’ (3%) and H-4 (2%) H-l with H-3 (lo%), H-2 (4%) and H-7 (3%), H-5’ with H-3’ (lo%), H-4 (1%) and H-l (l%), OAc (62.07) with H-15 (1%) (H-3’ and H-5’ protons of the epoxyangelate)]. These effects further established the relative position of PHYTO

30:R-Q

OAc

R’ R2

1

2

3

Epang H

Ang H

Epang

Ww

prop

MeBu

Epmz ival

6 R=H 7

H

I2 0 II 1311I,

10 9

\‘,I1

2

6

3’ I5

R=CH,OH

,*

’ 4

JQ

0

I4

6H 8 9

10 2,6,10 epi

2696

et al.

c.&ERO

Table 1. ‘H NMR spectral data of compounds 1-5 (400 MHz, CDC13, J-values) H

1*

2

3

1 2 3 4 I 8 8’ 9 9 10 12 13 14 15 OAc

4.03 br s 2.53 m 5.88 ddd 5.31 q 2.53 m 2.10 m 1.71 dq 1.82 dq 1.50 m 2.25 br dd 1.21 s 1.24 s 5.96 d 6.75 t 2.07 s 2.05 s 3.08 q 1.35 d 1.50 s

4.06 br s 2.57 dd 5.86 ddd 5.33 q 2.52 br dd 2.07 m 1.70 m 1.81 m 1.52 m 2.25 br dd 1.22 s 1.26 s 5.96 d 6.76 t 2.06 s 2.05 s 6.11 qq 2.02 dq 1.89 dq

5.05 2.51 5.98 5.39 2.32 2.08

OCOR

br s dd ddd

4t

5:

5.09 br s 2.53 dd

5.06 br s 2.55 dd

5.98 ddd 5.39 q 2.31 br dd

q m

m

2.08 m

1.75 m

> 1.75 m

1.53 m 2.18 m 1.14 s 1.28 s 5.93 d 6.75 t 2.08 s 2.07 s 2.41 dq 1.19 t

1.55 m 2.16 m 1.16 s

1.14 s 1.28 5.92 6.15 2.08 2.06 3.07 1.34 1 56

s

d

t s s

q d s

*In C,D6 H-2 2.32 dd, H-7 2.42 br dd. *OMeBu: 2.42 tq. 1.70 m, 1.50 m, 0.93 t, 1.20 d. $2.27 m, 2.16 m, 2.15 m, 0.98 d (6H). J[Hz]: 1,2=5; 2,3=3,4=4,15=14,15-1.5; Epang: 3,4=5; Ang 3,4=7; 3,5=4,5=1.5; = 7.5; MeBu = 2.3 = 2.5 = 3.4 = 7; iVa1: 3,4 = 7.

The ‘HNMR spectra of 3-5 (Table 1) differed from those of 1 and 2 by the downfield shift of the H-l signal and additional signals for a further ester group. Accordingly, we were dealing with derivatives of 1 where the hydroxy group was esterified with propionic, 2-methylbutyric or isovaleric acid. The presence of the ester residues at C- 1 caused, as expected, some shifts of neighbouring protons. The ‘H NMR spectrum of 6 (Experimental) indicated the presence of a trisubstituted benzene derivative with three vicinal protons. The nature of the substituents also followed from the ‘H NMR data while the relative position was determined from the chemical shifts of the aromatic protons and from the results of spin decoupling. Irradiation at 62.27 (H-7) changed the broadened doublets at 66.74 and 6.70 to clear double doublets and sharpened the H-8 signal at 64.96. The mass spectrum and the ’ 3C NMR spectrum also support the structure. The ‘H NMR spectrum of 7 (Experimental) was in part similar to that of 6. Notably, the signals assigned to the aromatic protons were the same. However, the signal of the methyl01 group was replaced by a double doublet at 65.23 and a pair of double doublets at 63.85 and 3.74, indicating the presence of a dihydroxyethyl group. This was supported by the mass spectrum which showed elimination of Hz0 and CH,OH. The different couplings of H-7 indicate that the configuration of the side chain is fixed by hydrogen bonds. The roots gave perezone (10)[lo]and the epimeric pipitzols 8 and 9 [S]. As there are no reports of the high field ‘HNMR data in the literature we have presented them in Table 2. The observed couplings of H-10 support the proposed stereochemistry. The co-occurrence of the isocedrenes l-5and of perezone and the related compounds 8 and 9 is remarkable as

Prop 2,3

Table 2. ‘HNMR spectral data of compounds 8 and 9 (400 MHz, CDCI,, &values) H

8

9

2 7 8 8’ 9 9’ 10 12 13 14 15

2.83 s 2.40 ddq

2.76 s 2.55 ddq

1.90 dddd 1.66 dddd 1.76 dddd 1.51 dddd 2.11 t 1.02 s 1.07 s 1.38 d 2.05 s

1.86 dddd 1.38 m 1.77 dddd 1.6 1 dddd 1.99 dd 1.05 s 1.07 s 1.32 d 2.05 s

J [Hz]: compound 8: 7,8 - 6; 7,8’ = 10; 7.14 = 7; 8,8’-14; 8,9-3.5; 8,9’-5; 8’,9=9; 8’,9’-6; 9.9’-13; 9.10=9’,10=8.5; compound 9: 7.8=7,8’-6; 7,14=7; 8,8’=12.5, 8.9-6; 8,9’-2; 8’,9-6; 8’.9’-9; 99-13: 9,10=2.5; 9’,10=10.

it is the first time that these compounds have been reported together from an Acourtia species. The phenolics 6 and 7 are related to the Smethyl coumarins which are widespread in the tribe Mutisieae, especially in the subtribes Nassauviinae and Mutisiinae [ll]. Perhaps A. nana is a link between Acourtia and Perezia. The suggestion that the Acourtia group is distant from Perezia [12] is, therefore, not supported by the chemistry.

2697

Sesquiterpcnes of Acourtia MM EXPERIMENTAL The

air-dried plant material was extracted at room temp. with MeOH-Et&-petrol (1: 1: 1). Separation was achieved as reported previously [13]. The extract of the aerial parts (5Og, collected near Monterrey, Mexico, in summer 1990, voucher Dominguez 8666, deposited in the Herbarium of Monterrey) gave 3 frs by CC. The first one gave 10 mg taraxasteryl and 5 mg lupeyl acetate by TLC. Fr. 2 gave by TLC (Et&petrol, 1: 1) three bands (2/l-2/3). HPLC (MeOH-H20, 4: 1, always RP 8, flow rate, 3 ml min-‘) of fr. 2/l gave 10 mg 4 (R, 10.4 min) and 7 mg 5 (R, 10.7 min) (not free from 4). HPLC of fr. 2/2 (MeOH-H,O, 4: 1) afforded 2 mg 3 (R, 5.5 min), 2 mg 2 (R, 8.9 min) and lmg of a mixt. of 4 and 5. HPLC of fr. 2/3 (MeOH-H,O, 4: 1) afforded 3 mg 6 (R, 0.8 min). TLC (Et,O) of fr. 3 gave 2 mg 7 (R, 0.38) and a crude fr. which gave by HPLC (MeOH-H,O, 4: 1) 20 mg 1 (R, 3.1 min). The extract of 75 g roots gave by CC and TLC (Et+petrol, 1: 3) 80 mg lo,50 mg 8 and 30 mg 9. la-Hydroxy-3a-epoxyangeloyloxy-l~,lS~~i~~oxy-l4~,l~epoxy-a-isocedrene (1). IR vFm4cm-‘: 3630 (OH), 1765 (OAc), 1745 (CO,R); MS m/z (rel. tit.): 404.184 [M-HOAc]+ (100) (talc. for Cz2H2s07: 404.184), 348 m-RCO$Il+ (76), 306 [348- ketene]+ (54), 264 (42), 263 (36), 245 (74), 229 (56), 217 (32), 201 (30); ‘%NMR (CDQ, C-1-C-15): 681.8, 60.1, 76.0, 119.3, 140.8, 54.6, 36.8, 32.3,27.7,67.7,42.1, 28.9,32.7,87.1,92.3; OAc: 21.3, 21.1, 170.2, 169.4; Epang (C-1’4-5’): 6169.5, 59.9, 59.6, 13.5, 19.1 (assigned by ZD-techniques). la-Hydroxy-3a-angeZoyloxy-l4a,l5~-diace~oxy-l4~,1~~~ oxy-a-isocedrene (2). IR v=~ ’ cm - I: 3630 (OH), 1765 (OAc), 1720

(C=CCOaR); MS m/z&l. int.): 388.189 [M-HOAc]+ (lO)(calc. for CZaH2s06: 388.189), 360 (5), 306 (32), 246 (lo), 83 [RCO]’ (loo). la-Propionyloxp3a-epoxyangeloyloxy-l4a,l5~-diace~oxy14/?,15a-epoxy-a-isocedrene (3). IR vg: cm-‘: 1760 (OAc,

COIR); MS m/z (rel. int.): 460.210 [M-HOAc]+ (100) (talc. for CZsH3208: 460.210), 404 [M-RCO,H]+ (81), 401 [460-OAc] + (34), 362 (78), 327 (64), 320 (62), 301(46), 246 (86), 229 (82), 218 (SO),202 (56), 57 [EtCO] + (98). 1a-[2-MethylbutyryZoxy]-3a-epoxyangeloyloxy-14a,15~-diacetoxy-14/3,15a-epoxy-a-isocedrene (4). IR v=; cm-‘: 1760

(OAc, C02R); MS m/z (rel. int.): 488.241 [M-HOAc]+ (68) (talc. for C27H3608: 488.241), 460 [488-CO]+ (12), 432 [M -RCO,H] ’ (37), 390 [432- ketene]+ (34), 348 (16 327 (20), 245 (50), 229 (42), 85 [RCO]+ (51), 57 [85-CO]+ (100); [a];@ - 33” (CHCIJ; c 0.86). la-lsovaleryloxy-3a-epoxyangeloyloxy-l4a,l5~-diace~oxy-

14p,15a-epoxy-a-isocedrene (5). IR vE‘:‘cm-‘: CO,R); MS m/z (rel. int.): 488.241 [M -HOAc]+

1760 (OAc, (65) (talc. for

C 27H 360 8: 488.241), 460 (lo), 432 (39), 390 (32), 245 (52), 85 (52), 57 (loo). 2-Hydroxy-6-methylbenzyl alcohol (6). Crystals, mp 107”; IR cwcl, cm-‘: 3610 (OH), 1590 (aromate); MS m/z (rel. int.): VIII., 138.068 [M]’ (84) (talc. for C8H1002: 138.068), 120 [M-HzO]+ (100),92[120-CO]+ (86),91 [M-CHO]+ (lOO), 77 [92-Me]+ (32), 65 [91-C2H2]+ (28k ‘%NMR (CDCII, C-l-C-8): 6135.8, 156.4, 114.5, 128.7, 122.1, 122.5, 19.2, 60.8; ‘H NMR (CD&): 66.74 (br d, H-3), 7.08 (t, H-4). 6.70 (d, H-5), 2.27 (br s, H-7) 4.96 (br s, H-8); .Z[Hz]: 3,4= 4,5 = 8; 3,7 = 7,8 = 1; 5,7= 1.5. 2-Hydroxy-6-methyl-[1,2-dihydroxyethyl]-benzene (7). IR CHCI,cm- ‘: 3610 (OH); MS m/z (rel. int.): 168.078 [M]’ (52) %., (talc. for C9H1203: 168.078). 150 [M-H,O]+ (18), 138 CM-CH,O]+ (54), 137 [M-CH,OH-J+ (lOO),121(68), 109 (66), 91(63); ‘H NMR (CDCl,): 66.74 (br d, H-3), 7.08 (t. H-4), 6.68 (br d, H-5), 2.27 (br s, H-7), 5.23 (dd, H-8), 3.85 and 3.74 (dd, H-9); J [Hz]:3,4=4,5=8; 8,9=9.5; 8,9’=3.5; 9,9’=11.

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