Revised structure of a diterpene from Euphorbia antiquorum

Phytochemiswy, Vol. 29, No. 12, pp. 3952 ~3953, 1990 Printed in Great Britain.

0

REVISED STRUCTURE EUPHORBIA MIN ZHI-DA,

Wu

RING,*

ZHENG

QI-TAI,*

MIZUO

OF A DITERPENE ANTIQUORUM MIzuNo,t

003 l-9422/90 $3.00 + 0.00 1990 Pergamon Press plc

FROM

MUNEKAZU IINUMAt and TOSH~YUKI TANAKA?

Department of Phytochemistry, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, China; *China Institute of Materia Medica, Chinese Academy of Medical Science, Beijing 100050, China; TDepartment of Pharmacognosy, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5 chome, Gifu 502, Japan (Received Key Word

7 May 1990)

Index---t‘uphorbin antiquorum; Euphorbiaceae; diterpene; antiquorin.

Abstract-A new diterpene, antiquorin, from Euphorbia antiquorum had been shown to be an atisine diterpene, cisfused between A and B rings, by spectral analysis. Further confirmation of its structure by X-ray diffraction showed that the A and B rings are not &-fused, but trans-fused (2). Therefore, the proposed structure for antiquorin must be revised.

In a previous paper Cl], we reported the structure of a new diterpene, antiquorin, isolated from Euphorbia antiquorum. The structure elucidation was based on the spectroscopic data. The conformation of the ring junction between the A and B rings was concluded by the CD spectral results to be cis-fused. By observation of the octant rule for a carbonyl group at C-3, the symbol and intensity of the Cotton effect at 300 nm was used for prediction of the states of the fused rings, and the predicted result led us to propose that the A and B rings were cis-fused. Thus the structure of antiquorin had been formulated as 1. In continuation of our studies on the structure of antiquorin, we considered the presence of two carbonyl groups at C-3 and C- 14 in 1 and the peak of the CD curve of two carbonyl groups, which was fully overlapped at 303 nm. The symbol and intensity of the Cotton effect at 303 nm were attributed to the total electron transition of two carbonyl groups, which could have led us to an incorrect conclusion about the junction between the A and B rings. For further confirmation of the structure of antiquorin, the X-ray diffraction was determined from the crystals recrystallized from methanol. Except for the junction between the A and B rings, the structure elucidated by the spectroscopic and the CD data was identical with that of the X-ray analysis. The computer generated drawing is shown in Fig. 1. The result of the X-ray diffraction analysis clearly revealed the A and B rings to be truns-fused and the C-20 methyl and H-5 to be in fl- and a-orientation, respectively. The skeleton of antiquorin belongs to an antisine diterpene, and the A and the B rings are in a chair conformation; the C and the D rings are in a twist-boat and a boat conformation, respectively. Hence the structure of antiquorin must be revised and formulated as 2. In addition, the X-ray drawing showed that one molecule of methanol (solvent) and two molecules of 2 were linked by intermolecular hydrogen bonding, and the bond length of oxygen at C-13 and oxygen of MeOH, and 0 (C-13 of another molecule of 2) and 0 (MeOH) are 2.714 and 2.641 bi, respectively. There is an intramolecular hydrogen bond between a hydroxyl group at C-13 and a

a 0

C

(If2 MeOH)

(3C-I8

Fig. 1. Computer-generated

carbonyl 2.778 A.

group

drawing of antiquorin.

at C-14, the bond

length

of which

is

EXPERIMENTAL

data. Orthorhombic system, space group P2,2,2,, cell dimensions are a=7.459 (I), b= 12.357 (2), c=20.637 (4) A, V=1901.80A3, Z=4. Intensity data were collected 1 < 0 < 57” by R3m/E hour-circle diffractometer. CuK,

3952

Crystallographic

Short Reports radiation with graphite-monochromated and 1502 independence reflections were recorded; 1390 with 183~~ (I) were considered as observed. The molecular structure was solved by direct method (SHELXTL program). Twenty-three non-hydrogen atoms were located from E map. Least-squares refinement and Fouriers synthesis gave the coordinate of all non-

hydrogen

3953 atoms,

R=0.0444.

The

M., Tanaka,

is

T., Iinuma,

M., Xu, G. and

Phytochemistry 28, 553.

Vol. 29, No. 12, pp. 3953-3955,1990 Printed in Great Britain.

OF

formula

REFERENCE

1. Min, Z., Mizuno, Huang, Q. (1989)

Phytochemistry,

CONGENERS

molecular

CHO 20 28 3’

0031-9422/90$3.00+0.00 0 1990Pergamon Press plc

NORDITERPENE

DILACTONES NAGI

FROM

PODOCARPUS

BAI-PING YING, IsA0 KUBO,* CHAIRUL,? TAKESHI MATSUMOTOt and YUJI HAYASHI*t Division of Entomology and Parasitology, College of Natural Resources, University of California Berkeley, CA 94720, U.S.A.; tFaculty of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558, Japan

(Received12 March 1990) Key Word Index-Podocarpus nagi; Podocarpaceae; root bark; norditerpene dilactone; 2,3-dehydro-16hydroxynagilactone F; nagilactone I; 16-hydroxynagilactone E.

Abstract-Three new norditerpene dilactones, 2,3-dehydro-16-hydroxynagilactone F, nagilactone I and ldhydroxynagilactone E were isolated from the root bark of Podocarpus nugi. Their structures were established on the basis of the spectroscopic analyses.

INTRODUCTION Many

biologically

active

norditerpene

dilactones

have

been isolated from various species of Podocarpus plants (Podocarpaceae) [14]. In particular, seeds and root bark of P. nagi were found to be rich sources of the dilactones. Norditerpene dilactones possess various biological activities such as anti-tumour [S, 61, plant growth regulatory [7, S] and insecticidal [9, lo] activities, and antifeedant activity against herbivorous animals [ll]. In our continuing search for bioactive substances from P. nagi, three new norditerpene dilactones were isolated. RESULTS AND DISCUSSION All three new components, compound 1-3, showed 19 skeletal carbon signals in their “CNMR spectra (Table l), including those of two types of lactone carbonyl carbons at 6 163-164 and 177-182. The compounds 1 and 2 give a characteristic electronic transition at 262-263 nm due to a dienolide system on the B/C ring (type C

dilactones) Cl], and compound 3 showed a transition at 220 nm, typical for a epoxyenolide system (type B dilactones) [l].

*Authors PHYTO29:12-R

to whom correspondence

should

be addressed.

Compound 1 has a molecular formula C,,H,,O, by high resolution mass spectrometry. The ‘HNMR spectrum showed typical splitting modes of the y-lactone ring protons over the A/B ring system (5-H at 6 1.95 and 6-H at 65.06) and two olefinic protons (7-H at 66.51 and 11-H at 65.92) and a carbinyl proton (14-H at 65.15) of the dienolide system on B/C ring with a-oriented side chain at C-14 [ll]. Two other olefinic protons at 65.8-5.9, coupled to each other, indicate an additional double bond on the ring A. Two carbinyl protons (at 63.93 and 4.14) suggest the presence of a primary carbinol group, which should be placed on the C-14 side chain (at C-16). The whole structure of compound 1 was finally derived by careful comparison of its 13CNMR data with those of previously known dilactones [12] (Table 1). The position of the ring A double bond (A’*‘) and partial structure of the C-14 side chain are supported by comparison with 16hydroxypodolide (6) [13]. The dienolide system on the B/C ring is confirmed from comparison with nagilactone F (4) [14] and 3-hydroxynagilactone F (5) [15]. Thus, compound 1 is 2,3-dehydro-16-hydroxynagilactone F. Compound 2 has a molecular formula C2,,Hz40, (HRMS). The presence of a methoxycarbonyl group is shown by a three-proton singlet at 63.63 and an additional carbonyl carbon at 6 172.6. A three-proton doublet at 6 1.46 (H,-17) indicates that the methoxycarbonyl group is located at the C-15 position. A secondary