Phytochemistry 59 (2002) 543–549

www.elsevier.com/locate/phytochem

Polyoxygenated cyclohexene derivatives from

Ellipeiopsis cherrevensis
Anake Kijjoaa,b, Julia Bessaa, Madalena M.M. Pintob, Choojit Anatachokec,
Artur M. S. Silvad, Graham Eatone, Werner Herzf,*
a
Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4099-003 Porto, Portugal
b
Centro de Estudos de Quı´mica Orgânica, Fitoquı´mica e Farmacologia de Universidade do Porto, 4050-047 Porto Portugal
c
Forest Products R&D Division, Royal Forest Department, Phahon Yothin Road, Chatuchak, Bangkok 10900, Thailand
d
Departmento de Quı´mica, Universidade de Aveiro, 3810 Aveiro, Portugal
e
Department of Chemistry, University of Leicester, University Road, Leicester LE17 RH, UK
f
Department of Chemistry, The Florida State University, Tallahassee, FL 32306-4390, USA

Received 9 August 2001; received in revised form 15 November 2001

Abstract
Aerial parts of Ellipeiopsis cherrevensis contained the polyoxygenated cyclohexenes zeylenol, ferrudiol and three analogs,
ellipeiopsols A, B and C. The C-1 stereochemistry of ferrudiol has been revised. # 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Ellipeiopsis cherrevensis; Annonaceae; Polyoxygenated cyclohexenes; Zeylenol; Ferrudiol; Ellipeiopsols A, B, C

1. Introduction 2. Results and discussion

Ellipeiopsis cherrevensis (Pierre ex Finet et Gagn.) R. The MeOH extract of the aerial parts on concentra-
E. Fries (Annonaceae, subfamily Annonoideae, tribe tion, precipitation of polar material from an EtOH–
Uvarieae) is one of only two species in the genus H2O solution, extraction with CHCl3 followed by col-
and is limited to Thailand and Cambodia. It has not umn and thin layer chromatography of the nonpolar
been studied previously. The genus is closely related fraction afforded five polyoxygenated cyclohexene deri-
to the genus Uvaria species of which have furnished vatives. The least polar substance was identified as zey-
acetogenins (Cavé et al., 1997) and polyoxygenated lenol (1a, Jolad et al. 1981; Pan and Yu, 1995a) by 1H
cyclohexene derivatives (Thebtaranonth and Thebt- and 13C NMR spectrometry, HMBC, COSY and
aranonth, 1986; Nkunya et al., 1987; Parmar et al., NOESY. A second substance was the new 3-acetate
1994; Liao et al., 1996, 1997; Pan and Yu, 1995a,b, analog 1b of zeylenol which we have named ellipeiopsol
1996; Pan et al., 1998; Zhou et al., 1998, 1999). Our A. Chemical shifts and coupling constants, HMBC and
study of the aerial parts has led to the isolation of the NOESY data (Table 1) showed that the acetate was
zeylenol (1a, Jolad et al., 1981), its new 3-acetate on C-3, the benzoate on C-7 and that conformer A
analog 1b, the new C-1 epi-derivatives 2a and 3a and resembled the predominant conformer, with H-3 pre-
ferrudiol (Schulte and Ganem, 1982; Schulte et al., dominantly axial and H-6 predominantly equatorial.
1982a) whose stereochemistry has been revised to 5a. A third constituent ellipeiopsol B was assigned struc-
ture 2a, epimeric at C-1 and C-6 compared with 1a,b, on
the basis of the NMR spectral data (Table 2) and the
formation of di- and triacetates 2b and 2c (Table 3). The
locations of the acetate at C-3 and the benzoate at C-7
* Corresponding author. Tel.: +1-850-644-2774; fax: +1-850-644-
were clear from the chemical shifts of H-3 and H-7a,b
8281. and from HMBC, COSY and NOESY experiments
E-mail address: [email protected] (W. Herz). while the chemical shifts and coupling constants
0031-9422/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved.
PII: S0031-9422(01)00465-4
544 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549

involving H-2 and H-4 indicated a stereochemistry at also clearly manifested in the chemical shifts of C-2, C-
these centers similar to that of 1a and 1b but with a free 6, both 1 ppm downfield from C-2 and C-6 in 1a,b, and
hydroxyl on C-2. On the other hand the coupling con- C-7, 3 ppm upfield from C-7 in 1a,b (see also Table 7).
stants involving H-5 and H-6 differed and the chemical The downfield shifts of C-2 and C-6 are negated in the
shift of H-6 indicated the absence of an esterifying case of the triacetate 2c because of the effect produced
function on the C-6 hydroxyl which was now alpha by acylation of a neighboring hydroxyl. The coupling
orientated. constants suggest that 2b exists entirely in conformation
The remaining problem was the stereochemistry at C- C ( R1=H, R2=Ac) while in 2c conformation C (
1. Chemical shifts of H-7a,b differed somewhat from R1=H, R2=Ac) merely predominates. In both 2b and
those reported for an isomer, ovarigranol G, which has 2c the NOESY spectrum exhibited a cross peak between
the C-7 stereochemistry of 1a and 1b (Pan et al., 1998). H-7 and H-3 as required by C.
In the NOESY spectrum the absence of a cross peak A fourth substance, ellipeiopsol C (3a), was obviously
between H-7 and H-2, the latter clearly b-orientated in closely related to 2a with the same stereochemistry at C-
2a and triacetate 2c, indicated that the stereochemistry 1, C-2, C-3 and C-6 but with the benzoate at C-6 instead
at C-7 was inverted with a preference for conformation of at C-7 as shown by the 1H and 13C NMR data in
C (R1, R2=H) because of the magnitude of J2,3 (7.5 Hz) Table 4. The signals of H-7a,b were now at considerably
in 2a. The difference in the stereochemistry at C-1 was higher field while H-6 had moved downfield. The
 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549 545

Table 1
1
H (300 MHz) and 13C NMR (75 MHz) data for compound 1b (CDCl3)

Position dH dCa NOESY COSYb HMBC

1 75.70 s
2 4.09 d (6) 70.47 d H-3 H-3, 6,7a, b (5) 3
3 5.44 m (6, 2.5, 1.5) 73.33 d H-2, 4 H-2, 4,7a, b (5) 2, 4, 5, AcCO
4 5.68 dt (10, 2.5) 126.66 d H-3, 5 2, 3, 5, 6
5 5.91 ddd (10, 4, 2) 129.73 d H-4, 6 H-4, 6,(3, 3, 7a, b) 1, 4
6 4.30 brd (4) 68.68 d H-5, 7a, b H-2, 5, 7a, b 1.4, 5
7a 4.74 d (12.2) 66.55 t H-2 H-2, 3, 6, 7b (5) 1, 2, 6 fCO
7b 4.67 d (12.2) H-2
C=O 167.51 s
10 129.57 s
20 , 60 8.10 dd (8, 1) 129.73 d H-2, 6,30 , 50 H-30 , 50 20 , 40 , 60 , fCO
30 , 50 7.40 dd (8, 8) 128.46 d 10 , 30 , 50 , fCO
40 7.55 dd (8, 1) 133.44 d H-30 , 50 H-30 , 50
3-Ac 1.99 s (3p) 171.77 s
21.03 q AcCO
a
Assignments by HETCOR.
b
Weak interactions in parentheses.

Table 2
1
H (300 MHz) and 13C NMR (75 MHz) data for compound 2a (CDCl3)a

Position
H dCa NOESY COSY HMBC

1 76.32 s
2 4.13 d (7.5) 74.72 d H-3 and/or H-5, H-6 1, 3,4, 7
3 5.80–5.83 m 73.98 d H-2 H-2 1, 4,5, 3-CO
4 5.66 dt (10.3, 2.5) 124.89 d
5 5.81 dd (10.3, 2.2) 132.25 d H-2, 6 H-4 1, 4,5, 3-CO
6 4.46 d (2.2) 72.73 d H-2, H-3 and/or H-5 H-5 4, 5
7a 4.77 d (12) 63.37 t H-3 and/or H-5 H-7b 1, 2,6, fCO
7b 4.67 d (12) H-2
3-CO 166.58 s
7-CO 167.67 s
10 , 10 129.47 s H-2, 6,30 , 50 H-30 , 50 20 , 40 , 60 , fCO
20 , 60 200 , 60 8.00 dt (8, 1.4) 129.75, 129.67d H-2, 3,30 , 50 , 300 , 500 H-30 , 50 , 300 , 500 70 , 60 , 2,6, 40 , 4,3-CO, 7-CO
30 , 50 , 300 , 500 7.36 td (8, 1.4) 128.39, 128.27 d 10 , 1, 30 , 3, 5, 3-CO, 7-CO
40 , 400 7.49 tt (8, 1.4) 133.24, 133.13 d H-30 , 50 , 300 , 500 AcCO
a
Assignments by HETCOR.

chemical shifts of C-1, C-2 and C-6 in 3a exhibited the the hydroxyls on C-1 and C-2. Our own measurements,
expected changes produced by acylation at C-6 and including the previously unrecorded 13C NMR spectra,
deacylation at C-7 while conversion to a diacetate 3b for ferrudiol and its new diacetate are listed in Table 6.
and a triacetate 3c mirrored the shifts observed in the Although interpretation of the NOESY spectra was
conversion of 2a to 2b and 2c (Tables 5 and 7). The ring difficult due to superposition of signals the existence of a
coupling constants in the case of 3b and 3c indicate that cross peak between the H-3 and H-7 signals was evi-
the predominant if not exclusive conformations are C dent, an observation which could only be explained by
(R1=H, R2, R3=Ac resp. R1, R2, R3=Ac with Ac on reversing the stereochemistry at C-1 as in formulas 5a
C-7) as also shown by strong cross peaks between H-3 and 5b, with conformation C (R1, R2 on C-2=Ac, R2
and H-7 in the NOESY spectra. on C-6=Bz) predominant. Moreover the chemical shifts
The remaining substance was identical with ferrudiol of C-1, C-2, C-6 and C-7 were similar to those of 2a and
based on the 1H and 13C NMR spectra (Table 5), mp the shift changes on conversion of 5a to 5b closely par-
and rotation for which structure 4 including the abso- allel the shift changes which accompany the conversion
lute configuration was derived twenty years ago on the of 2a to 2c as is evident from the compilation in Table 7;
basis of the 1H NMR spectrum, formation of a tetra- in fact the chemical shifts in the 13C NMR spectra of 2c
and a pentabenzoate and CD measurements (Schulte et and ferrudiol diacetate are very similar.
al. 1982a,b). The stereochemistry assigned to C-1 was Structure 4 for ferrudiol was apparently based on the
based on the facile formation of a carbonate involving assumption that formation of a carbonate between the
546 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549

Table 3
1
H (300 MHz) and 13C NMR (75 MHz) data for compounds 2b and 2c (CDCl3)a

2b 2c

Position dH (2b) dC (2b)a dH (2c) dC (2c)a NOESY

1 75.37 s 82.14 s
2 5.67 d (8.8) 74.19 d 6.49 d (7.5) 70.14 d
3 5.91 ddd (8.8, 5.8, 2.2) 71.28 d 5.90 ddd (7.5, 4.7, 2.4) 71.13 d H-2,7a, b, 2́, 2, 6́, 6
4 6.00 dt (10.4, 2.2) 127.45 d 6.03 dt (10.5, 2.4) 126.76 d
5 5.76 dt (10.4, 2.2) 128.39 d 6.03 dt (10.5, 2.4) 128.16 d
6 5.70 dd (5.0, 2.4) 76.25 d 6.56 dd (5, 2.5) 68.88 d
7a 4.70 d (12.3) 64.23 t 4.90 d (11.9) 60.97 t H-2,3
7b 4.63 d (17.3) 4.71 d (11.9) H-3
3-CO 165.96 s 165.91 s165.71 s
7-CO 167.11 s
10 ,100 129.38 s, 129.28 s 129.43 s, 129.29 s
20 ,60 ,200 ,600 8.09 d, 8.07 d (8.2, 1.5) 129.79 d 8.00–8.07 m 129.79 d, 129.72 d
30 ,50 ,300 ,500 7.42–7.49 m 128.59 d, 128.55 d 7.42–7.51 m 128.57 d, 128.29 d
40 ,400 7.55–7.60 m 133.50 d, 133.46 d 7.55–7.62 m 128.57 d, 128.29 d
2-Ac 1.90 s (3p) 20.61 q, 170.30s 2.01 s corresponds to 20.62 q
6-Ac 2.08 s (3p) 20.92 q, 171.53 s 2.02 s corresponds to 21.98 q
7-Ac 2.06 s corresponds to 20.79 q
a
Assignments by HETCOR and HMBC.

Table 4
1
H (300 MHz) and 13C NMR (75 MHz) data for compound 3a (CDCl3)a

Position dH
Ca NOESY COSY HMBC

1 75.54 s
2 4.19 d (8) 76.62 d H-3 H-3 C-7
3 5.78 m 73.98 d C1C2
4 5.82 dt (10, 5, 2.4) 127.18 d H-5
5 5.72 dd (10.5, 2.4) 128.47 d H-4 C-1, 3,6
6 5.82 m 75.64 d C-2.7
7a 4.17 d (12) 62.80 t H-7 C-1, 2,6
7b 4.09 d (12) C-1, 2,6
3-CO 166.17 s
6-CO 166.61 s
10 129.49 s
20 , 60 8.02 dd (8, 1.4) 129.78 s H-30 , 50 , 300 , 500 H-30 , 50 , 300 , 500 7-CO, C-20 , 60 , C-40
30 , 50 7.39 tt (8, 1.4) 128.44 d H-30 , 50 , 300 , 500 C-10 , C-100 , C-30 , 50 , C-300 , 500
40 7.53 td (8, 1.4) 133.28 d
100 129.36 s
200 , 600 8.00 dd (8) 129.72 d H-30 , 50 , 300 , 500 , H-3 H-30 , 50 , 300 , 500 3-CO, C-200 , 600 , C-400
300 , 500 7.39 tt (8, 1.4) 128.34 d C-10 , C-100 , C-30 , 50 , C-300 , 500
400 7.53 td (8, 1.4) 133.39 d
a
Assignments by HETCOR.

hydroxyls at C-1 and C-2 of the cyclohexene ring 3. Experimental

required a cis relationship between the two hydroxyls.
However, it has been relatively easy to construct a 3.1. General experimental procedures
Dreiding model of the carbonate from 5a. In the model
1
the cyclohexene ring is a half-chair with the substituents H and 13C NMR spectra were recorded at ambient
at C-3 and C-6 quasi-equatorial, C-7 axial and the car- temperature on a Bruker AMC instrument operating at
bonate ring somewhat distorted and strained. The 300.13 and 75.47 MHz, respectively, EI mass spectra
model of a carbonate is easier to form from the old were measured on a Hitachi Perkin-Elmer RMU-6 M
structure, the carbonate ring being essentially planar, instrument. HRMS samples were run using +FAB
but the cyclohexene ring is a somewhat distorted boat ionization with Xe gas at 6 kV on a KRATUS
with C-7 and the ester function on C-6 both axial and CONCEPT III, 2 sector mass spectrometer. The accel-
opposed and the ester on C-3 remaining equatorial. erating voltage was 8 kV. Rotations were obtained on a
 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549 547

Polarotronic Universal Schmidt and Haensch polari- 3.2. Plant material

meter. Si gel for column chromatography was Si gel 60
(0.2–0.5 mm) Merck, for analytical and preparative TLS Aerial/parts of Ellipeiosis cherrevensis (Pierre et Finet
Si gel G-60 GF 254 Merck. et Gagn.) R. E. Fries were collected in Sakon-Nakorn

Table 5
1
H (300 MHz) and 13C NMR (75 MHz) data for compounds 3b and 3c

3b 3c

Position
H
Ca
H
Ca NOESY

1 75.10 s 81.13 s
2 5.69 d (8.5) 73.74 d 6.47 d (6.5) 69.70 d H-7a,H-7b
3 5.78 ddd (8.5, 4.5, 2.2) 70.84 d 5.79 ddd (6.5, 4.5, 1.8) 70.71 d H-2,H-6,H-7a,H-7b,2.01,2.02 s
4 6.02 ddt (10.5, 2.2) 127.64 d 6.04 ddt (10.3, 3, 1.8) 126.83 d
5 5.78 dt (10.5, 2.2) 128.10 d 5.95 ddd (10.3, 1.8) 127.75 d
6 5.88 dd (4.5, 2.2) 76.27 d 6.70 dd (3.2, 2) 68.50 d
7a 4.60 d (11.8) 63.16 t 4.91 d (11.8) 60.42 t H-2́,6́,2,6
7b 4.40 d (11.8) 4.40 d (11.8) H-2́,6́,2,6
3-CO 165.91 s 165.86 s
6-CO 166.92 s 165.71 s
10 ,100 129.03 s, 129.22 s 129.31 s, 129.28 s
20 ,60 ,200 ,600 8.07 dd, 8.03 dd (8.4, 1.1) 129.19 d, 129.80 d 8.01–8.07 m 129.80 d, 129.72 d
30 ,50 ,300 ,500 7.43–7.51 m 128.59 d, 128.56 d 7.43–7.501 m 128.56 d, 128.52 d
40 ,400 7.57–7.65 m 133.77 d, 133.49 d 7.57–7.61 m 135.53 d, 133.45 d
2-OAc 2.09 s 20.79 q, 170.17 s 2.11 s 20.72 q, 169.23 s
7-OAc 1.93 s 20.67 q, 171.19 s 2.02 s 20.79 q, 170.00 s
1-OAc 2.01 s 22.03 q, 169.68 s
a
Assignments by HETCOR and HMBC.

Table 6
1
H (300 MHz) and 13C NMR (75 MHz) data for compounds 5a and 5b

5a 5b
a
Position
H
C COSY dH dCa NOESY

1 76.04 s 82.10 s
2 4.31 d (8.5) 75.43 d H-6 6.59 d (7) 70.08 d
3 5.82–5.85 m 76.77 d H-2 5.93 dt (10.3, 2.4) 71.13 d H-2, 7a, b,2, 6,2, 6,2, 6
4 6.01 dt (10.2, 1.6) 127.91 d H-5, 6 6.09 dt (10.3, 2.4) 126.93 d
5 5.88 dt (10.2, 1.6) 128.30 d 5.97 dt (10.3, 2.4) 128.14 d H-6
6 5.82–5.85 m 72.80 d 6.86 dd (5, 2.4) 69.10 d
7a 4.83 d (12) 62.68 t H-7b 5.06 d (11.8) 61.23 t H-3
7b 4.75 d (12) 4.77 d (11.8) H-3
3-CO 167.28 s 165.83 s
6-CO 166.52 s 165.42 s
7-CO 166.59 s 165.91 s
10 129.51 s 129.35 d
20 , 60 7.99 dd (8.5, 1.5) 129.85 d 7.99–8.05 m 129.82 d
30 , 50 7.47 tt (8, 1.5) 128.46 d H-20 , H0 , 60 , 2000 , 3000 , 5000 , 6000 7.38–7.53 m 128.51 d
4 7.60 tt (7.5, 1.5) 133.43 d H-30 , 50 7.53–7.61 m 133.49 d
100 129.34 s 129.32 s
200 , 600 8.10 dd (8.5, 1.5) 129.95 d H-300 , 500 7.99–8.05 m 129.73 d
300 , 500 7.34 tt (7.5, 1.5) 128.43 d 7.38–7.53 m 128.51 d
400 7.52 tt (7.5, 1.5) 133.13 d H-300 , 500 , 3000 , 5000 7.53–7.61 m 133.44 d
1000 128.88 s 129.16 s
2000 , 6000 7.91 dd (8.5, 1.5) 129.63 d H-3000 , 5000 7.99–8.05 m 129.73 d
3000 , 5000 7.32 tt (7.5, 1.5) 128.33 d 7.38–7.53 m 128.51 d
4000 7.47 tt (8, 1.5) 183.12 d 7.53–7.61 m
 133.32 d

2:06 s 169:70; 22:07 q
1-OAc
2:03 s 169:32; 20:72 q
2-OAc
a
Assignments by HETCOR and HMBC.
548 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549

Province, Northeast Thailand, in August 1999. A vou- Table 7

cher specimen CA-10-2542 was deposited in the herbarium Comparison of C-1, C-2, C-6 and C-7 frequencies (CDCl3)
of the Royal Forest Department, Bangkok, Thailand. Compound C-1 C-2 C-6 C-7

3.3. Extraction and isolation 1a 75.79 70.62 68.79 66.53

1b 74.70 70.47 68.68 66.57
2a 76.32 74.72 72.73 63.37
Air dried whole aerial parts (400 g) were percolated 2b 75.37 74.19 76.25 64.03
by MeOH to exhaustion (3.5 l). Evaporation at reduced 2c 82.14 70.14 68.88 60.97
pressure furnished 35 g of crude extract which was dis- 3a 75.54 76.62 75.69 62.80
solved in warm EtOH (700 ml) to which was added 750 3b 75.10 73.74 76.27 63.16
3c 81.63 69.70 68.50 60.42
ml of H2O containing 27 mg of lead acetate and 8 ml of 5a 76.04 75.43 72.80 62.68
glacial acetic acid. The solution was kept in a dark 5b 82.10 70.08 69.10 61.23
chamber for 48 h and filtered, the filtrate was con-
centrated at reduced pressure to remove EtOH and
extracted with CHCl3 (4300 ml). The combined 3.6. Ellipeiopsol B (2a)
CHCl3 extracts were dried (Na2SO4) filtered and eva-
porated at reduced pressure to give a syrupy mass (4 g) Gum, []b 139.7 (CHCl3, c=5.8 g/100 ml); HRMS
which was applied to Si gel 60 (300 g) and eluted with +FAB 385.12877, C21H21O7 requires 385.12873; 1H
petroleum ether–CHCl3 and CHCl3–Me2O, 250 ml NMR and 13C NMR spectra in Table 2. Acetylation of
fractions being collected as follows: Frs. 1–40 (petrol– 20 mg of 2a with Ac2O-pyridine overnight and work-up
CHCl3, 3:2), 41-80 (petrol–CHCl3, 1:4) and 81–96 in the usual manner followed by purification of the
(CHCl3–Me2O, 9:1). Frs. 6–9 were combined and pur- crude product by TLC (CHCl3–petrol–HCO2H, 95:5:
ified by TLC (Si gel, CHCl3–petrol–EtOAc–HCO2H, 0.1) afforded 11 mg of diacetate 2b and 6 mg of triace-
8:1:1:0.1) to give ferrudiol (5a) (57 mg) and (32 mg) of a tate 2c as gums whose 1H and 13C NMR spectra are
mixture. Frs 10–13 were combined and purified by TLC listed in Table 3; EI–MS of 2b, m/z calc for C25H24O9,
(Si gel, CHCl3–petrol–EtOAc–HCO2H, 8:1:1:0.1) to 468; found m/z (%) 468 (M+, 12), 451 (7), 409 (32), 346
give more ferrudiol (42 mg) and 21 mg of the same (55), 333 (40), 304 (16), 286 (93), 273 (11), 244 (85), 211
mixture. Fr 41 was purified by TLC (Si gel, CHCl3– (6), 183 (10) 163 (30), 141 (11), 122 (12), 105 (100), 77
Me2O–HC2OH, 8:2:0.1) to give 3a (112 mg) and 2a (38 (27); EI–MS of 2c, m/z calc. for C27H28O10, 510; found
mg). Fr 42 on TLC (Si gel, CHCl3–MeOH–HCO2H, m/z (%) 510 (M+, 5), 466 (10), 389 (35), 348 (12), 286
8:2:0.1) furnished more 3a (41 mg), more 2a (53 mg) and (17), 244 (14), 226 (16), 164 (17), 122 (18), 105 (100), 77
53 mg of a mixture. Frs. 43 and 44 were combined and (23).
purified by TLC (Si gel, CHCl3–Me2O–HCO2H, 8:2:0.1)
to give zeylenol (1a, 186 mg) and 96 mg of the mixture 3.7. Ellipeiopsol C (3a)
from Fr. 42. Frs. 45–47 were combined and purified by
TLC (Si gel, CHCl3- Me2O-HCO2H, 8:2:0.1) to give Gum, []b 130 (CHCl3, c=1.10g/100 ml); HRMS
more zeylenol (21 mg), 22 mg of the mixture from fr. 42, +FAB 385.12868, C21H21O7 requires 385.12873 1H
and 1b (34 mg). NMR and 13C NMR spectra in Table 4. Acetylation of
21 mg of 3a with Ac2O-pyridine overnight and work-up
3.4. Zeylenol (1a) in the usual manner followed by purification of the
crude product by TLC (CHCl3–petrol–HCO2H, 95:5:
White crystals, mp 137–140  C (CHCl3–petrol), [a]b 0.1) afforded 10 mg of diacetate 3b and 8 mg of triace-
113 (CHCl3; c 1.35 g/100 ml) (lit Jolad et al., 1981, tate 3c as gums whose 1H and 13C NMR spectra are
mp 144–145  C, [a]d 113 ),+FAB MS (NBA): calc. listed in Table 5; ; EI–MS of 3b, m/z calc. for C25H24O9,
for C21 H2O+H+: 385. Found: 385. The 1H NMR 468; found m/z (%) 468 (M+, 6), 451 (8), 409 (5), 395
spectrum corresponded to that reported in the literature (8), 346 (5), 335 (4), 245 (20), 226 (7), 164 (10), 122 (12),
(Pan and Yu, 1995b); the 13C NMR spectrum corre- 105 (100), 77 (30); EI–MS of 3c, m/z calc. for
sponded to that reported earlier (Jolad et al., 1981); C27H26O10, 510 found m/z (%) 510 M+, 12), 466 (12),
however, the values of
C-2 and
C-6 need to be 451 (7), 389 (10), 348 (20), 328 (12), 286 (8), 244 (5), 226
interchanged as shown by HETCOR and HMBC. (77) 122 (6), 105 (100), 77 (21).

3.5. Ellipeiopsol A (1b) 3.8. Ferrudiol (5a)

Yellowish gum, []b +22.8 (CHCl3, c=1.27 g/100 White crystals, mp 192–195 , (CHCl3, petrol), [a]b
ml); HRMS: +FAB 323.11305, C16H19O7 requires 156.9 (CHCl3, 0.217 g/100 mg) (lit Schulte et al., 1982,
323.11308; 1H NMR and 13C NMR spectra in Table 1. mp 191–192, []-141 ) +FAB 489.15488, C281H25O8
 A. Kijjoa et al. / Phytochemistry 59 (2002) 543–549 549

requires 489.15494, 1H NMR and 13C NMR spectra in Liao, Y.-H., Xu, L.-Z., Yang, S.-L., Sun, N.-S., 1996. Studies on the
Table 6. Acetylation of 25 mg with Ac2O-pyridine chemical constituents of Uvaria grandiflora. Zhongcaoyao 27, 824
(Chemical Abstracts 1996–125, 323022c).
overnight and work-up in the usual manner followed by
Liao, Y.-H., Xu, L.-Z., Yang, S.-L., Dal, J., Zhen, Y.-S., Zhu, M.,
purification of the crude product by TLC (CHCl3–pet- Sun, N.J., 1997. Three cyclohexene oxides from Uvaria grandiflora.
rol-HCO2H, 7525:0.1) afforded 19 mg of diacetate 5b as Phytochemistry 45, 729.
a gum whose 1H and 13C NMR spectra are also listed in Nkunya, M.H.H., Weenen, H., Koyl, N.J., Thijs, L., Zwanenburg, B.,
Table 6; ; EI–MS of 3b, m/z calc. for C32H28O10, 572; 1987. Cyclohexene epoxides, (+)-pandoxide, (+)-b-senepoxide and
found 572 (M+,7) 513 (12), 467 (10), 452 (7), 408 (5), ()-pipoxide from Uvaria pandensis. Phytochemistry 26, 2563.
Pan, X.P., Yu, D.-Q., 1995a. Two new oxygenated cyclohexenes from
390 (7), 348 (15), 331 (15), 285 (21), 269 (17), 244 (16), Uvaria grandiflora. Chinese Chemical Letters 6, 309 (Chemical
226 (32), 164 (21), 122 (35), 105 (100), 77 (30). Abstracts 1995–123, 29641d).
Pan, X.P., Chen, R.-Y., Yu, D.-Q., 1998. Polyoxygenated cyclohex-
enes from Uvaria grandiflora. Phytochemistry 47, 1063.
Pan, X.P., Yu, D.-Q., 1995b. Two new oxygenated cyclohexenes from
Uvaria grandiflora. Phytochemistry 40, 1709.
Parmar, V.S., Tyagi, O.D., Malhotra, A., Singh, S.K., Bisht, K.S.,
Acknowledgements Jain, R., 1994. Novel constituents of Uvaria species. Natural Pro-
ducts Reports 11, 219.
We want to thank Fundação para Ciência e Tecnolo- Schulte, G.R., Ganem, B., 1982. Studies on highly oxidized cyclohex-
gia (Unidade de I&D No. 226/94), POCTI (QCA III) enes. Structure and absolute configuration assignments. Tetra-
hedron Letters 23, 4299.
and FEDER for support. Schulte, G.R., Ganem, B., Chantrapromna, K., Kodpinid, M., Suds-
vansri, K., 1982a. The structure of ferrudiol, a highly oxidized con-
stituent of Uvaria ferruginea. Tetrahedron Letters 23, 284.
Schulte, G.R., Kodpinid, M., Thebtaranonth, C., Thebtaranonth, Y.,
References 1982b. Studies on highly oxidized cyclohexenes. Constitution of a
new key metabolic intermediate. Tetrahedron Letters 23, 4303.
Thebtaranonth, C., Thebtaranonth, Y., 1986. Naturally occurring
Cavé, A., Figadère, B., Laurens, A., Cortes, D., 1997. Acetogenins cyclohexene oxides. Accounts of Chemical Research 19, 84.
from Annonaceae. In: Herz, W., Kirby, G.W., Moore, R.E., Ste- Zhou, G.-X., Chen, R.-Y., Yu, D.Q., 1998. Two new polyoxygenated
glich, W., Tamm, Ch. (Eds.), Progress in the Chemistry of Organic cyclohexenes from Uvaria calamistrata uvacolol A, uvacolol B.
Natural Products. Vol. 70. Springer Verlag, Wien, New York, p. 82. Chinese Chemical Letters 6, 309 (Chemical Abstracts 1999, 131,
Jolad, S.D., Hoffmann, J.J., Schram, K.H., Cole, J.R., Tempesta, 308830v).
M.S., Bates, R.B., 1981. Structure of zeylenol and zeylene, con- Zhou, G.-X., Chen, R.-Y., Yu, D.Q., 1999. New polyoxygenated
stituents of Uvaria zeylanica (Annonaceae). J. Org. Chem. 46, cyclohexenes from Uvaria calanistrata. Journal of Asian Natural
4267. Products Research 1, 227 (Chemical Abstracts 1999, 131, 167690k).