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Tcnahedron Letters. Vol. 33, No. 28, pp. 4011-4012. 1992Printed n Great Britain

WlWO39,92 $5.00 + .oOPergamonPressLtd

Spirodensifolins A and B, New Rearranged P inguisaneSesquiter penoids, from the Liverwort Frullanoides densifoliaMotoo Tori, Hernita Arbiyanti, Zenei Taira, and Yoshinori Asakawa*

Faculty of Pharmaceurical Sciences. Tokushima Bunri University. Yamawhiro cho. Tokushima 770, Japan

Keywords: Spircdensifolin A, Spirodensifohn B. ~r&unoi& de&&o, Liverwort, Pinguisane type sesquiterpeneAbstract: New rearranged pinguisane type sesquiterpenoids, spirodensifolms A (1 Jand B. have been isolated and their relativestereostructures elucidated by means of extensive spectroscopic and X-ray crystallographic analyres of 1 .

In continuing the chemical studies on the Hepaticae, we have investigated the chemical constituents ofFrullanoides densifoliu Radii (belonging to the Lejeuneaceae family) collected in Bolivia. We have isolated twonew compounds, spirodensifolins A (1) and B (2) and established their structures on the basis of spectralevidence and X-ray crystallographic analysis of 1.

The ether extract of F. &n.@olia (dry weight I SOg) was chromatographed on a combination of silica gel,Sephadex LH-20 and HPLC, which resulted in the isolation of two new sesquiterpenoids, spirodensifolins A (1,9Omg) and B (2,5mg), together with the previously known ptychanolide (3, 13.6mg).*

Spirodensifolin A (1) was obtained as a crystal, mp 193-195C [a]22,-40.60(r. 1.33. CHC!,). Themolecular formula, C,,Hz20,, was determined by the presence of a molecular ion peak at m/z 322.1425 inHRMS. The H NMR spectrum of 1 revealed the presence of two secondary methyl groups at 6 1.03 and 1.1 I,two tertiary methyl groups at 6 1.15and 1.32,an acetoxyl group at 6 2.17 ( I730 cm ), and five methine protonsattached to the carbon bearing oxygen functions at 6 3.93 (s), 4.03 (t, I 2.0). 4.38 (d, .I 2.2), 5.09 (d, / 1.7), and5.55 (d, J 2.2). The IR and C NMR spectra suggested the presence of a y-lactone group 11785 cm-; &78.8 (d)and 175.8 (s)]. The absence of hydroxyl absorption in the IR spectrum indicated that the remaining oxygenatoms were attributed to ether linkages. This was further confirmed by the signals at 6,59.2 (d), 79.4 (d), and88.8 (d) in the 13C NMR spectrum. In the HMBC spectrum, the protons of the C-12 methyl group showedconnectivity to C- 1, C-9, C-8, and C-7 and the C- 13methyl protons showed connectivity to C- 1, C-X, and C-Z.It also showed connectivity between the protons of the C-14 methyl group and the carbons C-4, C-9, C-8, andC-3. The C-15 methyl protons showed connectivity to C-4, C-9, and C-S. Furthermore, the presence ofcorrelation between the proton at C-4 and the carbons C- IS, C-9, C- IO, C-8, and C-3, and the proton at C-7 andthe carbons C-4, C-9, and C-IO is indicated in its spectrum. Both protons at C-IO and C-l 1showed connectivityto C-6, and connectivity between the proton at C-10 and the carbon C-5 was also observed. On the basis of theabove data, 1 was suggested to be a rearranged pinguisane type sesquiterpene having a spirolactone moiety. Itsstereochemistry was determined by the presence of NOES between (i) H-3 and the following protons: H-2, H- 13,and H-14, (ii) H-7 and H-12, (iii) H-13 and H-12, (iv) H-13 and H-2, and (v) H-14 and H-15, indicating that a!1methyl groups in 1 h&d the p-orientation and the acetoxyl group was thus a-oriented. Furthermore, an NOE wasobserved on H-4 upon irradiation of H-10. However, both c(- and p-isomers of the epoxide can explain theresult of the NOE experiment. Therefore, the X-ray crystallographic analysis of 1 was carried out.) The result isshown in the Fig., and the relative stereochemistry of 1 including the epoxide ring is clearly established asdepicted in the formula,

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Spirodensifolin A (1) Spirodensifolin B (2) Ptychanolide (3) Fig. Perspective drawing of 1

The molecular formula, C,,H,,O,, of spirodensifolin B (2), [a] D -36.8(c 0.3 I, CHCI,), was determinedby HRMS [(m/z 262.122 1 (M)]. The IR spectrum showed the band due to a 1 lactone (I 790 cm-) group. TheH NMR spectrum indicated the signals due to a secondary methyl group (6 1.04), wo tertiary methyl groups (61.18 and 1.23), four methine protons attached to the carbon bearing oxygen functions (6 3.90, 4.08, 4.24, and5.58), and an exomethylene group (6 5.12. 5.28). The above spectral data resembled those of 1, except for thepresence of two protons of an exomethylene group and the absence of a secondary methyl group and an acetoxylgroup. Thus, the above results together with the co-occurrence of 1 in the same liverwort established thestructure of spirodensifolin B to 2.

It is very interesting to note that ptychanolide (3). whose structure was established by X-ray analysis byTakeda et al., was also found in the present liverwort, although the stereochemistry at C-5 was different fromthose of 1 and 2. They are presumably biosynthesized from the pinguisane type sesquiterpenoids? by the C-Cbond rearrangement as discussed by Connolly.

This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health andWelfare, Japan. We acknowledge Dr. S. R. Gradstein. Institute of Systematic Botany, University of Utrecht,The Netherlands, for his collection and identification of Bolivian Fml/unoide.s den$i~fi,lia. One of us (H.A.) isalso indebted to Iwatani Foundation for the financial support during one year.

REFERENCES1. Y. Asakawa, Chemical Constituents of the Hepaticae, in Progress in the Chemistry ofOrganic Natural

Products, 42, (W. Herz, H. Grisebach and G. W. Kirby, eds) pp. l-285, Springer-Verlag, Wien (1982).2. R. Takeda, H. Naoki, T. Iwashita, K. Mizukawa, Y. Hirose, T. Ishida, and M. Inoue, Bull. Chem. Sot.

Jpn., 56, 1125 (1983).3. Recrystallized from ether-dichloromethane as thin leaf-like crystals. Crystal data for 1; orthorhombic,u=13.625(6), h=31.051(4), (=7.580(3) A, space group E&2,2,, D,=1.335, p(Mo-Ka)=0.9426. Of 2454

total unique reflections, 850 were considered to be observed at the level of F,p3o(F,,). The structure wassolved by using the direct methods and the refinement was carried out by using the full-matrix leastsquares to R=0.0999, Rw=O. 103 I. The supplementary material has been deposited at the Cambridge DataCentre .

4. Y. Asakawa, M. Toyota, M. Kano, and T. Takemoto, P hytoc~hemistry, 19, 265 1 ( 1980).5. J. D. Connolly, Monoterpenoids and Sesquiterpenoids from the Hepaticae, in Bryophytes: Their Chemistry

and Chemical Taxonomy (H. D. Zinsmeister and R. Mues, eds), pp. 42-58, Oxford University Press,New York (1990).

(Received in Japan 31 January 1992)