Pergamon

0040-4039(94)02258-5

Tetrahedron Letters. Vol. 36. No. 4. pp. 583-586. 1995 Elsevier Science Ltd

Printed in Great Britain 0040-4039/95 $9.50+0.00

TASHIRONIN, A PLAUSIBLE BIOSYNTHETIC PRECURSOR OF ANISATIN-TYPE

SESQUITERPENES

Yoshiyasu Fukuyama, * Naomi Shida, and Mitsuaki Kodama*

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770, Japan

Abstract: The structure of tashironin (1), isolated from the wood oflll icium tashiroi, has been elucidated by

extensive analysis of spectroscopic data. Tashironin represents a presumed biosynthetic precursor of anisatin-

type sesquiterpenes which consists of a 2-oxatricyclo[4.3.1.04,9]heptane skeleton.

A convulsive principle oflll icium anisatum, anisatin (3) 1, has attracted much attention due to its

characteristic biological activity as well as its complicated structure interesting as target of synthesis. 2, 3

Although anisatin and its congeners have been postulated to be biosynthesized from a tricarbocyclic precursor

2, 4 the biosynthetic route leading to anisatin skeleton has been still obscure because any tricarbocyclic

sesquiterpenes have not been found in lllicium species. 5 Herein, we wish to report the isolation and structure

of a novel tetracyclic sesquiterpene 1 named tashironin, which possesses the precise skeleton corresponding to

a biogenetic precursor 2 of anisatin-type sesquiterpenes.

The isolation of tashironin (1) (27 mg) from an EtOAc soluble portion (67 g) of the methanol extract of

the dried woods of lllicium tashiroi was achieved according to the previously reported procedures. 6

Tashironin (1) 7 had the molecular formula C22H2606 determined by HR-FAB-MS and its spectral data

showed the presence of hydroxyl (3522 cm -1) and carbonyl (1718 cm-1; 8C 210.7) groups, and a benzoate

moiety [232 and 282 nm: 51-I 7.43 (2H, t, J -- 8.6 Hz), 7.58 (1H, t, J = 8.6 Hz) and 7.98 (2H, d, J -- 8.6 Hz); iSC

165.6]. In addition to the above functional groups, the 1H NMR spectrum of I contained the signals due to

two tertiary methyl groups [~H 1.05 and 1.24], two isolated methylene groups [~H 2.14 and 2.61 (each d, J --

18.8 Hz); 3.86 and 4.21 (each d, J = 8.8 Hz)], a carbinyl methine group coupled to a hydroxyl proton [81-I 4.07

(d, J = 2.0 Hz) and 3.91 (OH, d, J = 2.0 Hz)]. Moreover, 2D DQFCOSY and 13C-1H COSY verified the

O

/ ~ ' ~ - - - | ~ 8 1 6 H O H H O ~ H o

2 ~ 12 ¢ . ",,

4~ 5 ~ 7~, . , HO 13 u

1 R = COPh 2 3

583

584

Table 1. 13C NMR data (100 MHz, in CDC13) of I and 13C-1H long-range correlation in the HMBC a)

Carbon 8C Correlated H Carbon f~C Correlated H

1 38.7 H-8~, 15 11 110.2 H-10, 12, 14

2 31.1 H-I, 313, 15 12 9.8 - 3 34.1 - 13 13.5 H-14 4 85.7 H-2~, 3, 8, 10, 13, 14, OH 14 74.3 H-13 5 60.9 H-12, 13, 14, OH 15 14.6 H-1 6 54.5 H-12, 13, 14 1' 165.6 H-3', 7' 7 210.7 H-8a, 8~, 12 2' 129.2 8 44.1 H-l , 10 3', 7' 128.6 9 52.4 H-2, 80t, 8~, 10, 15, OH 4', 6' 130.1

10 76.4 H-l, 8~t, 8~1, OH (3.91) 5' 133.8

a) JC-H = 8 Hz.

15 CH 3

. / I , . 7 1

H2~ 2

H2 C 3 •

A

.o\ o ........................... o - I

/ - - ~ 9 ! / 8 i " ~ / . . C ~ 0 / ! 2 0 ............. ::::~C 11

HO 12

CH3 13

Fig. 1 The consecutive linkage of the quaternary carbons C9-C4-C5-C6-C 11 and the counterparts bonded to C-11 clarified by HMBC are showed by bold and dotted lines, respectively.

presence of a partial structural unit A. The 13C NMR and DEPT spectra of I indicated the presence of five

quaternary carbons (8C 52.4, 54.5, 60.9, 85.7, and 110.2), the latest one of which was assigned as a

hemiacetal-type carbon based on its low field resonance. Taking the aforementioned spectral data and co-

occurrence of anisatin in I. tashiroi into consideration, 1 was presumed to belong to either anisatin- or

psudoanisatin-type sesquiterpene. The spectral data of 1, however, had no resemblance to those of both types

of sesquiterpene. In order to make up the carbon skeleton of 1, the HMBC was performed so as to give the long-range 13C-1H correlations as summarized in Table 1. Namely, the quaternary carbon signal at 8(2 52.4

(C-9) was correlated to the doublet methyl (H-15), the carbinyl methine (H-10), and the isolated methylene

(H-8), which in turn showed a cross peak with the C-7 carbonyl signal. Thereby, C-9 must be connected to

C-l, C-10, and C-8 which linked up with the C-7 position. Another quaternary carbon (C-4) appended with

585

the hydroxyl group showed correlations to the H-3, 8, and 10 signals, indicating the bond connectivity of C-4

with C-3 and C-9. The oxymethylene signals (H-14) showed clear correlations to the quaternary carbons (C-

4, C-5, and C-6) to form a C14-C5 bond, and the latter two carbons (C-5 and C-6) further had cross peaks to

the methyl signals (H3-13 and H3-12), which in turn correlated to C-4, C-6 and C-5, C-7, C-11 respectively.

These HMBC correlations resulted in forming the consecutive C-C bonds between the quaternary carbons

denoted by bold lines in Fig. 1. The HMBC correlations of the remaining hemiacetal-type carbon with H-10

and H-14 could link C-11 to C-10 and C-14 via a C-C bond and an ether bond, respectively, as shown by

dotted line in Fig. 1. Finally, the benzoate group was found to attach to the C- 11 position since NOE was

observed for the aromatic H-3' and/or H-7' upon irradiation of the H3-12 at ~H 1.24. These results gave rise to

the plane structure 1, which consists of a novel 2-oxatricyclo[4.3.1.04,9]heptane skeleton.

Molecular model discloses that, by its formation, the tricyclic system itself sets up the relative

configurations at the chiral centers C-5, C-6, C-9, C-11. The relative stereochemistry of the remaining chiral

carbons at C-1, C-4, and C-10 was deduced by difference NOE experiments as shown in Fig. 2. In particular,

the hydroxyl group attached to C-10 is disposed into the more hindered inside space, and thereby its resistance

against acetylation and benzoylation can be reasonably rationalized. Hence, the spectral data mentioned

above corroborated the structure 1 for tashironin.

O 1'

H H / ..HO.ll .,.., Io',, k H S H n ~ 1 4 / u",,l_ -,,'N l

Fig 2. Stereochemistry of 2 based on NOEs indicated by arrows.

Although the biosynthesis of anisatin and its related sesquiterpenoids has not been investigated, it is

generally accepted that anisatin 1 could be biosynthesized from a bisabolane through a tricarbocyclic

precursor 2 after breaking the C6-C 11 bond as shown in Fig. 3. 4 Thus, the isolation of tashironin (1), anisatin

(3), and its related sesquiterpenes 6 from the same source is of considerable significance and throws light on

the biogenesis of anisatin-type sesquiterpenes.

This work is partially supported by a Grant-in-Aid for Scientific Research (No. 05680516) from the

Ministry of Education, Science and Culture, Japan.

586

~ -.........-.i~

11

Anisatin

Bisabolane Acorane /

1 -'~---- ~

2

Fig. 3 Plausible biosynthetic route of anisatin 3 and tashironin 1 via a common precursor 2

References and Notes

1. K. Yamada, S. Takada, S. Nakamura, and Y. Hiram, Tetrahedron, 24, 199 (1968).

2. J. F. Lane, W. T. Koch, N. S. Leeds, and G. Gorin, J. Am. Chem. Soc., 74, 3211 (1952).

3. H. Niwa, M. Nishiwaki, I. Tsukuda, T. Ishigaki, S. Ito, K. Wakamatsu, T. Mori, M. Ikagawa, and K.

Yamada, J. Am. Chem. Soc., 112, 9001 (1990).

4. T. K. Devon and I. A. Scott, "Handbook of Naturally Occurring Compound: Volume II Terpenes",

Academic Press, New York, 1972, p 56.

5. Allo-cederol isolated from Juniperus rigidia has been known as the sesquiterpene bearing this carbon

skeleton. B. Tomita and Y. Hirose, Phytochemistry, 12, 1409 (1973).

6. Y. Fukuyama, N. Shida, M. Kodama, M. Kido, M. Nagasawa, and M. Sugawara, Tetrahedron, 48, 5847

(1992).

7.1: mp 196-197°; [ot]~ ° - 5.6 ° (c 1.15, EtOH); HR-FAB-MS: m/z 409.1591 [M + Na] + (calcd. 409.1627 for

C22H2606Na), 387.1806 [M + H] + (calcd. 387.1807 for C22H2706); ~.~°Hnm: 232 (e 10900), 282 (e 750);

v ~ c m 1:3522 (OH), 1718 (C=O), 1639, 1601; 1H NMR (400 MHz, CDCI3) {i 1.05 (3H, s, H3-13), 1.21 (3H,

d, J = 7.1 Hz, H3-15), 1.24 (3H, s, H3-12), 1.50 (1H, ddd, J = 12.4, 9.0, 3.8 Hz, H-3~), 1.73 (1H, dddd, J =

12.7, 9.8, 8.3, 3.8 Hz, H-213), 2.04 (1H, ddddd, J = 12.7, 9.8, 9.0, 6.6 Hz, H-2ct), 2.14 (1H, d, J = 18.5 Hz, H-

8~), 2.29 (1H, ddq, J = 9.8, 9.8, 7.1 Hz, H-l), 2.56 (1H, ddd, J = 12.2, 8.3, 6.6 Hz, H-3[~), 2.61 (1H, d, J =

18.5 Hz, H-8~), 3.86 (1H, d, J --- 8.8 Hz, H- 14), 3.91 (1H, d, J = 2.0 Hz, OH), 4.07 (1H, d, J = 2.0 Hz, H-10),

4.21 (IH, d, J = 8.8 Hz, H-14), 7.43 (2H, t, J = 8.6 Hz, H-4', 6'), 7.58 (1H, t, J = 8.6 Hz, H-5'), 7.98 (2H, d, J =

8.6 Hz, H-3', 7').

(Received in Japan 20 September 1994; revised 27 October 1994; accepted 11 November 1994)