Te~~~nLettcTs,Vo131.No.39.~56~~-~~~2 1990 Printed in Great Britain

STRUCTURE OF IL~ICINOL~~E A, A NOVEL SESQUITERPEN~ LACTONE FROM THE BARK

OF ILL.KIUM TASHIBOI

Yoshiyasu Fukuyama,* Naomi Shida, Mitsuaki Kodama,*

Masaru Kido,+ and Masakazu Nagasawa t

Faculty of Pharmaceutical Sciences, Tokushima Bunri University,

Yamashiro-cho, Tokushima 770, Japan; 'Otsuka Pharmaceutical Co., Lid.,

Kagasuno, Tokushima 771-01, Japan

ABSTRACT: A New skeletal sesquiterpene, illicinolide A (I) has been

isolated from Illicium tashiroi. The structure of illicinolide A as

elucidated by extensive 2D NMR data was confirmed and its absolute configu-

ration established by X-ray analysis of the p-bromobenzoyl derivative.

The toxic plant, Illicium anisatum L. elaborates a structurally

unique sesquiterpene, anisatin, I,2 which is well known as a toxic

constituent and also recent extensive study on the chemical constituents of

Illicium species by Kouno and his collaborators3t4 has led to the discovery

of a number of the anisatin and majucin-like sesquiterpenes as well as of a

new type one.5 Our independent search for pharmacologically interested

substances in the MeOH extract of Illicium tashiroi (Yaeyamashikimi in

Japanese) collected in Ishigaki Island, Japan has resulted in the isolation

of a new type of sesquiterpene I named illicinolide A. Herein, we wish to

report the structure of 1.

Illicinolide A (I), mp I33 - 135'C, [cr]D -49.6 (c 0.58, EtOH), was

formulated as CI6H24OS established by HRFABMS (m/z 345.1566 [M+ + HI), and

its IR spectrum showed the presence of hydroxyl groups (3230, 3370 cm-') and

a y-lactone moiety (1750 cm-' ) which was supported by the 13C NMR data (6

179.4). The 'H NMR spectrum6 of 1 contained signals due to a secondary, a

tertiary, and a methoxy methyl groups at 6 I.22 (d, 5=7.3 Hz), I.72 (s), and

3.47 (s), respectively, in addition to ABX and A2X spin systems and two

sets of vicinal carbinyl methine protons derived from DQFCOSY. The carbons

attached to these protons were assigned by DEPT and 'H-13C COSY,'I which also

revealed the presence of three quaternary carbons at 6 46.3, 59.7, and 79.0.

The partial units obtained thereby could be assembled together with the

remaining four quaternary carbons by HMBC, and then 2D NOESY coupled with

difference NOE made relative stereochemistry of 1 assignable. These results

enabled us to propose the novel structure of illicinolide A as depicted in

5621

5622

l:R=H

2: R =p-BrBz

Fig. ORTEP drawing of the molecular

structure of 2.

1. In order to confirm the tentative structure, an X-ray analysis of a p-

bromobenzoyl derivative 2, colorless prisms from ether/CH2C12, mp >25O"C,

was attempted. The crystal and intensity data were derived from measure-

ments on a Rigaku AFCSS diffractometer with graphite-monochromated MoKa

radiation. Crystal data: C30H30010Br2, monoclinic, space group P21(#4), a =

7.15 (l), b = 18.29 (2), c = 11.622 (8) A, 8 = 104.25 (9)O, Dx = 1.601

g/cm3, z = 2, and u(MoKa) = 27.77 cm-'. A total of 749 reflections were

used for the structure analysis. The structure was solved by direct methods

using the TXSAN crystallographic software package of Molecular Structure

Corporation. The final refinement cycle gave R = 0.065. The absolute

configuration of the molecule as shown in Fig. was determined by Bijovet's

anomalous dispersion method based on the observed and calculated structure

factors of 10 Friedel pairs. While the most part of the strucutre including

the stereochemistry is consistent with the previously reported anisatin and

majucin, illicinolide A is related rather to noranisatin' derived as an

oxidative degradation product from anisatin. This abnormal structure can be

rationalized biogenetically by assuming that the C-7 carbon in 1 is somehow

originated from the C-11 in normal anisatin skeleton. 2

References and notes

l.J. F. Lane, W. T. Koch, N. S. Leeds, and G. Gorin, J.Am. Chem. Sot., 74, 3211 (1952). 2.~. Yamada, S. Takada, S. Nakamura, and Y. Hirata, Tetrahedron, 24, 199 (1968). 3.1. Kouno and N. Kawano, J. Chem. Sot. Perkin Trans I, 1988, 1537. 4.1. Kouno, N. Baba, M. Hashimoto, N. Kawano, M. Takahashi, Ii. Kaneto, and C.-S. Yang, Chem. Pharm. Bull., 38, 422 (1990) and references cited therein. 5.1. Kouno, K..,Mori, N. Kawano, and S. Sato, Tetrahedron Letters, 30, 7451 (1989). 6. H NMR (400 MHZ, C D N):6 1.22 (3H, d, J=7.3, H-14), 1.34 (lH, bt, J=2.4, H-9), 1.72 (3H, s, H-353, 2.21 (lH, dd, J=11.5, 6.5, H-118), 2.60 (IH, d, Jell.5, H-lla), 2.93 (IH, dg, J=9.0, 7.3, H-l), 3.47 (3H, s, OCH ),

a 4.02 (2H, d, J=2.4, H-8), 4.34 (lH, d, J=7.3,

H-6), 4.61 (lH, dd, J=9.0, -6, H-2), 4.59 (lH, d, J=7.3, H-7), 4.72 (lH, d, J=6.5, H-lo), 5.24 (lH, d, 5~4.6, H-3). 7.13C NMR (100 MHz, C5D N):6 8.2 (C-14), 18.1 (C-15), 36.2 (C-11), 36.5 (C-l), 45.6 (C-9), 46.3 (s-5), 55.0

66.0 (C-8), 70.2 (C-6), 78.2 (C-2), 79.0 (C-4), 82.8 , 83.8 (c-3), 105.0 (c-7), 179.4 (C-13). 8.K. Yamada, S. Takada, and

Y. Hirata, Tetrahedron Letters, 1965, 4785.

(ReceivedinJapan12 June1990)