Piscicidal cis-clerodane diterpenes from solidago altissima l: absolute configurations of 5α, 10α-cis-clerodanes

Tetrahedron Letters,Vo1.25,No.26,up 2809-2812,1984 Printed in Great Britain

PISCICIDAL

cis-CLERODANE

ABSOLUTE

DITERPENES

CONFIGURATIONS

oo4o-4039/84 $3.00 + .OO 61984 Peraamon Press Ltd.

FROM SOLIDAGO AwISSIMA

L:

OF 5a,lOa-cis-CLERODANES

a* b Shunichi Manabea Masami Kazuib and Takao Matsuzaki Chikao Nishino aMitsubishi-Kasei Institite of Life Sciencis 11 Minamiooya, Machida, Tokyo 194, Japan b Research Center of Mitsubishi Chemical Industries, 1000 Kamoshida-cho, Midori-ku, Yokohama Kanagawa 227, Japan

Sumnary : From Solidago aZtissima L. (Compositae), a new 5a,lOa-cis-clerodane diterpene (Solidagolactone VIII) and known solidagolactones were isolated as piscicidal constituents. The structures of the constituents including absolute configurations were determined, and a revised structure was given to solidagolactone VII. Continuing weed, SoZidago

our investigations1 aZtissima

of the biologically

L. (a goldenrod,

ents with the 5a,lOa-cis-clerodane

Compositae),

skeleton

active constituents we isolated

[activity,

around

four piscicidal

limit) to killifish

(Gryzias Zatipes)] from the aerial parts of the plant. to be a new compound

from the plant.

They revised

trans-clerodanes

proposed

cal transformations, solidagolactones lactones structure

VIII

spectral

and VII,

giving

respectively.

by piscicidal

(except for flowers)

were required.

lactone VIII):

new (2)

data, the structures

and a revised

of the piscicidal

(2 -t 2a) structure

to solidago-

is made of on the absolute

diterpenes. from the methanol

The physical

-27.4”

further

extract

of the aerial parts

(2.7 g) and 5_ (1.4 g) were first isolated 5c on Florisil 5a, silicage15b and alumina .

AgN03(10%)-silicage15d

data of the compounds

(c 0.3)6a;

vmax 1780, 1750, 1705, 1650, 1640, 1268 cm-'; (3H, s, H3-20),

et a2.2

of the extract

(250mg),

C25H3605; [a],

by Yamamura

of the solidagolactones to cis-clerodanes from 4 . In this paper, on the basis of chemi-

(3.4 Kg) of the plant, G

To isolate la_ (124mg) and2

One (12) of the

and Okazaki

activity,

chromatographies

constitu-

The others were

and V (6_), isolated

Also the first description

of the 5a,lOa-cis-clerodane

after successive

IV (3

and X-ray analytical

are reported,

By monitoring

graphies

the structures

by McCrindle3

VIII.

named as solidagolactone

VII (2a),

to known solidagolactones,

rank

10 ppm in TLm (median tolerance

four was elucidated assigned

of a heinous

1.21 (3H, s, y3-19),

were as follows:

UV: Amax 209.1

k

nm (E 25700)6b;

chromato-

(solidago-

IR (film):

’ H NMR6c: 6 0.88 (3H, d, J = 6.4, H3-17), 1.03

1.29 (3H, s, H3-18),

(CH~)], 1.89 [3H, m, W3(CO)C=CH(CH3)],

and silicage15e

1.81 [3H, d, J = 6.8, CH3(CO)C$H

2.75 (lH, bs, H-3), 4.75

(2H, d, J = 1.8, H-16),

5.40 (lH, dd, J = 2.4, 3.5, H-6), 5.84 (lH, tt, J = 1.5, 1.8, H-14), 6.90 [lH, qq, J = 1.2, 6.8, CH3(CO)C&(CH3)]; CH(CH3)]

MS: m/z 416 (M+), 401 (M+-CH3),

(exact MS: 333.2076,

(solidagolactone mp 119"-120"

VII):

C20H2g04),

C25H3605

(hexane-EtOAc);

(Anal,Calcd.:

[a]

1745, 1695, 1640, 1272, 1248 cm- P;

-28.4O

C, 72.08; H, 8.71.

333 [M+-CH,(CO)C=

(317.2118,

C20H2g03).

3

Found: C, 72.48; H, 8.76);

(C 1.2); imax 211.8 nm (E 26500);

vmax (KBr) 1780,

6 0.88 (3H, d, J = 6.6, H3-17), 1.03 (3H, s, H3-20), 1.22

(3H, s, H E3 -19), 1.31 (3H, s, H3-18), CH3(CO)C
398 (Mf-H20),

317 CM+-CH,(C~,)=CH(CH,)]

1.97 [3H, m, fZ3(CO)&CH(CH3)],

2.03 (3H, d, J = 7.0,

2.75 (lH, bs, H-3), 4.76 (2H, d, J = 1.8, H-16), 5.44 (lH, dd, J = 2.5,

2809

2810 3.6, H-6), 5.84 (lH, tt, J = 1.5, 1.8, H-14), 6.07 [lH, qq, J = 1.2, 7.0, C;3(CO)C&f(CH3)]; 416 (M+), 401 (M+-CH~),

m/z

2

(solidagolactone

mp 137"-138'

IV):

398 (M+-~~0),

333 CM+-CH,(CO)C==CH(CH,)],

C20H3003(Anal. Calcd.: C, 75.43; H, 9.50.

(hexane-EtOAc);

[al0 t3.6'

= 6.8, H3-17),

(hexane);

[alO t125.2"

285.

(c 1.2); XmaX 205.3 nm

1750, 1705, 1668, 1640 cm-'; 6 0.83 (3H, d,J = 6.8, H3-17), 4.75 (2H, d,J = 1.8,

(3H, d, J = 1.2, H3-18), 1.8, H-14); m/z

316 (M+) (316.2032),

The presence

1.15

(2H, d, J = 1.8, H-16),

2

(solidagolactone

(E

20800);

V): C20H2803;

vrnax (film) 1780,

1.22 (6H, s, H3-19 and 20), 1.52

H-16), 5.63 (lH, m, H-3), 5.82 (lH, tt, J = 1.5,

301 (M+-CH3),

of a B-substituted

vrnax (KBr) 3530,

1.03 (3H, s, H3-20),

3.71 (lH, t, J = 2.8, H-6), 4.75

1.70 (3H, bs, H3-18),

5.83 (2H, m, H-3 and H-14); m/z 318 (M+), 300 (M+-H20), mp 106.5"-107"

Found: C, 75.84; H, 9.68);

(e 0.9); imaX 204.9 nm (E 18100);

3480 (sh), 1800, 1750, 1640 cm-'; 6 0.88 (3H, d,J (3H, s, H3-19),

317 [M -CH3(C02)C~~(~~3)].

287.

AayB -butenolide

ring was suggested

in IR (vmax 1800 or

1780, 1750 or 1745, 1640 cm-') and 'H NMR (6 4.76 or 4.75, 5.82 - 5.84) of all the compounds. The other IR and 'H NMR spectral

VII,

lactones

characteristics

IV and V, respectively,

in &, 2a

,5_and 6_ resembled

and the spectra were identical

those in solidago-

with those presented

by

Yamamura2. Similarity 333, 3171.

between

E

skeleton

Chemical

splitting

G

was observed

in their mass spectra

In the 'H NMR spectra, similar resonances

on the clerodane shifts,

6.07 in g

and 2

and its pendant methyls patterns

and coupling

were due to protons on angelate

to protons

on tiglate

moiety.

also appeared

416 (M+), 401, 398,

[m/z

for the signals

of protons

(H-3, H-6, H3-17, H3-18, H3-19 and H3-20). constants

moiety,

whereas

Thus the structure

2

of the signals

at 6 1.97, 2.03 and

those at 6 1.81, 1.89 and 6.90 in

could be given to the new compound.

,.. ^n LP y :A

1o 1

OR

k

R=C

l,b R=CO

2

R=CwH

2b

R=CO

E

R=H

qjtko

XH

i@%.

R

OR

2

R=,Y-OH

J,

R=COxH

6

R==O

k

R=H

Figure 1. molecular 6

‘2 ‘J.

R’=

H

R1=OC+?

R2= COOH

(3. &COOH

ORTEP drawing structure

of the

of p-bromobenzoate

2811

The four piscicidal derived

compounds

were structurally Epoxybutenolides,

from 5_ (Jones' oxidation).

into epoxyfurano-compounds, of a s-substituted

c7

correlated.

and 2,b8, with DIBAL

furan ring was indicated

in the

2

with a hydroxyl

group

(z)'

V (2) was

and 2,", were respectively

(THF, -35" -+ -ZOO, 3.5 hr).

converted The presence

IR band (vmax 880 cm-') and 'H NMR Signals

[6 6.25 (lH, m), 7.21 (lH, m), 7.35 (lH, t, J = 1.5)] of G compound

Solidagolactone

and 3

which yielded

the same

(film) 3480 cm-'; 6 1.37 (3H, S, H3-18),

[vmax

3.01 (lH,

d, J = 2.4, H-3), 4.13 (lH, t, J = 2.6, H-6), 5.44 (lH, bs, OH)] on LiA1H4 reduction Solidagolactone

3hr).

acid (CH2C12, According

room temp, 1 hr), 2 yielded

to the usual epoxidation

was expected

On treatment

IV (5~) was also correlated with z.

to have an epoxide

(yield ratio, 1.7:1). 12 alcohols , the main product, 2,

3a1' _ anddl

two epoxides,

mechanism

(THF, 15',

with p-bromoperbenzoic

of homoallylic

ring with the same configuration

(s-epoxide)

as the B-OH group.

In the IR (CHC13) of 3a, an absorption of intramolecular hydrogen bond of the 0H13 was shown -1 which was unaffected by dilution, but the spectrum showed no absorption at 3600 ,

at 3470 cm

cm-l (free OH) which

appeared

3475 cm-l which was affected suggested

by a sharpened

proton of2 molecular

resonated hydrogen

the u-oriented

at d around

bonding

epoxide

Because

identified to 2

bonding

nature

in very lower field

These evidences

suggest

chemical

shift

the presence

by

the structure

Yamamura

was

the OH

of an intraepoxide

In C& no such interaction to that of 3a.z

a furano-derivative

of solidagolactone

of

a free form of the B-OH

(6 5.44) of the OH proton of 2

(THF, -35" + -25", 3.5 hr) to yield

proposed

of the 0H14 in 2

(6 5.41), whereas

the B-OH group and the oxygen atom of a B-oriented

3.02 [lH, d, J = 2.4, H-33) in ,3$.

Accordingly,

as 33.

from2

signal

1.8 (m).

between

In 6, a weak IR band was observed at

The hydrogen

[B 1.40 (3H, s), 3.11 (lH, d, J = 5.1)] causes

of similar

was reacted with DIBAL

IR (CHC13) of2.

broad singlet

ring (6 1.37 (3H, s, H3-18),

group.

in the

by dilution.

which was

VII was revealed

to revise

et a2.2

In cis-clerodane was determined

with a confirmed establish effects

type diterpenes, the absolute configuration for a 5B,lOs-cis-clerodane 15 by a structural correlation of this compound with (-)-hardwickiic acid 16 absolute structure . For 5a,lOa-cis-clerodanes, McCrindle17 attempted to

for2

the absolute

configurations

of solidagoic

acid A (2)

and B (u)

in the CD curves of a C-2 ketone and a similar enone derivative.

ambiguities

in the entire

effects were affected Crystalline established

absolute

by possible

p-bromobenzoate

by X-ray analysis

for the piscicidal

compounds

structure,

since interpretation

conformations

from 2,

a = 11.782

for the signs of Cotton

and its absolute

Hence, the absolute

as the first example

Crystal datalg: Monoclinic,

configuration

(2), b = 10.526

ite monochromated ties of Friedel

(2ac150") were measured Cu-Ka Radiation

with an Enraf-Nonius

and an w/20 scanning

pairs, 2373, independent

reflections

structure

was solved by the direct method

including

all non-hydrogen

and refined

atoms with anisotropic

with isotropic

temperature

factors.

the calculated

positions.

The absolute

and calculated

structure

factors

The final R-index configuration

of 23 Friedel

Intensity

After averaging

factors

the intensi-

supported

The

least squares methods,

and 5 hydrogen

for 2373 reflections was determined

pairs which

data for using graph-

(IF/) were used.

by the full-matrix

temperature

(2) 1, B = 96.13

(AD4 diffractometer

IFI >3a

was

diterpenes.

(3), c = 10.273

technique.

with

structure

could be determined

for 5u,lOa-cis-clerodane

(l)", U = 1267 i, Z = 2, DC = 1.356, lo = 27.191 cm-', space group P 21. 5539 reflections

some

for the derivatives.

(i)18 was obtained

(Fig. 1).

based on Cotton He left however

atoms

were 0.097 at

by comparing the absolute

the observed

2812

configurations

shown in Fig. 1.

AcknowZedgment: NMR spectra

We wish to thank Prof. S. Yamamura,

of solidagolactones

Keio University,

for the IR and 'H

VII, IV and V. References and Notes

C. Nishino and T. Tsuzuki, BEtyu-&g&u, 40, 62 (1975). :: M. Niwa and S. Yamamura, Tetrahedron Letters, 22, 2789 (1981). T. Anthonsen and R. McCrindle, Acta Ckem. Seana’., 23, 1068 (1969). :: T. Okazaki, A. Ohsuka and M. Kotake, Nippon Kagaku Kaiski, 1973, 584. 5. a: EtOAc (active fraction) after hexane; b: hexane-EtOAc 10% stepwise; Activity, 70% and 80% EtOAc in hexane. c: Benzene-EtOAc 5% stepwise; Activity, 30-40% (&), 40-50% (to subsequent chromatographies to isolate l,a and ,!S)and 55-60% (2) EtOAc in benzene. d: HexaneEtOAc 5% stepwise; Activity, 90-95% (Q) and 100% (to final chromatography to obtain,6) EtOAc in hexane. e: Benzene-EtOAc (4:l); Activity, fractions lo-13 (j). 6. a: In EtOH at 25". B: In EtOH. c: In CDCl3 at 90 MHz. Coupling constant (J) in Hz. 7. L$: C25H3604 (Anal. Calcd.: C, 74.96; H, 9.06. Found: C, 75.17; H, 9.21); mp 84.5"-86" (hexane); [alo -31.9" (e 0.4); vmax (film) 1710, 1655, 1270, 880 cm-l; 6 0.85 (3H, d, J = 6.6, H3-171, 1.04 (3H, s, Hs-20), 1.27 (3H, s, H3-19), 1.29 (3H, s, Hs-18), 1.80 [3H, m,CHs(CO)C=CH(CHa)l, 2.75 (lH, bs, H-3), 5.41

a.

9. ;tb: CzoH3003; [aID -28.0" (c 0.9); vmax (film) 3480, 875 cm-l; 6 0.85 (3H d, J = 7.0, Hs-17), 1.02 (3H, s, Hs-20), 1.19 (3H, S, Hs-19), 1.37 (3H, S, H3-l8), 3.01 (lH, d, J = 2.4, H-3), 4.13 (lH, t, J=2.6, H-6), 5.44 (lH, bs, OH), 6.25 (lH, m, furanoid), 7.20 (lH, m, furanoid), 7.35 (lH, t, J = 1.5, furanoid); m/z 318 (M+) (318.2192), 300 (M+-H20). 10. 3a: C20H3004; [CZ] -27.2" (C 1.1); (CHC13) 3470, 1785, 1750, 1640 cm-l; 6 0.87 (3H x J = 6.8, Hs-177, 1.00 (3H, S, H3???7, 1.14 (3H, S, Hs-19), 1.37 (3H, S, H3-l8), 3.02' (lH, d, J = 2.4, H-3), 4.13 (lH, bt, J = 2.7, H-6), 4.75 (2H, d, J = 1.8 H-16, 5.41 (lH, bs, OH), 5.83 (lH, tt, J = 1.5, 1.8, H-14); m/z 334 (M') (334.2145), 316 (M+-H20). 11. 8: CzoH3004; [a]D -17.1" (e 1.3); vmax (CHCls) 3600, 3475, 1785, 1750, 1640 cm-l; 6 0.87 'I3H, d, J = 6.4, H3-171, 0.97 (3H, S, H3-20), 1.16 (3H, S, Hs-19), 1.40 (3H, S, H3-l8), around 1.8 (lH, OH), 3.11 (lH, d, J = 5.1, H-3), 3.82 (lH, bt, J = 2.6, H-6), 4.73 (2~, d, J = 1.8, H-16 4, 5.82 (lH, tt, J = 1.5, 1.8, H-14) m/z 334 (M+) (334.2183), 319 (M+-CH3), 316 (M -H20). I, 12. E.W. Colvin, S.M. Malchenko, R.A. Raphael and J.S. Roberts, J. Ckem. Sot. Perkin 1973, 1989. 1374. 13. P.C. Chamberlain, M.L. Roberts and G.H. Whitham, J. Ckem. SOC. (ET), m, 14. S. Mynderse and R.E. Moore, J. Org. Ckem., Q., 4359 (1978). 15. M.S. Henderson, R.D.H. Murray, R. McCrindle and D. McMaster, Can. J. Ckem., 51, 1322 A.B. Anderson, R. McCrindle and E. Nakamura, J. Ckem. Sot. Ckem. Corm., 1974, (1973). 453. R. McCrindle, E. Nakamura and A.B. Anderson, J. Ckem. Sot. Perkin I, 1976, 1590. Letters, 1968, 2681. 16. R. Misra, R.C. Pandey and S. Dev, Tetrahedron 17. T. Anthonsen, M.S. Henderson, A. Martin, R.D.H. Murray, R. McCrindle and D. McMaster, Can. J. Ckem., 3, 1332 (1973). Found: C, 62.75; H, 6.31; Br, la. $,: C27Hss0sBr (Anal. Calcd.: C, 62.67; H, 6.43; Br, 15.44. 242.9 (e 17200), 200.6 nm (E 34000); 15.50); mp 192.5" - 194"; [a] -10.7' (C 0.5); A (KBr) 1790 1750 1715 7645 1598 1490 cmmTx 6 0.89 (3H, d, J = 6.6, H3-17), 1.07 i"!#; s, Hs-20),'1.26 [3H, s: H&), l.jO (3H, s, &18), 2.75 (1H d J = 1 5 H-3) 4.76 (2H, d, J = 1.8, H-16), 5.57 (lH, dd, J = 2.4, 3.5, H-6), 5.86 (iH, tt,'J'= 1.5: 7.97 (2H, dm, J = 8.7, aromatic); m/z 518 1.8, H-14), 7.58 (2H, d, J = 8.7, aromatic) (M++2)/516 (M+) (l:l), 503 (M++2-CHs)/501 (M+-CH,) (l:l), 333 (M+-BrCsHbCO), 316 (M+-BrC6H4C02H). 19. The atomic co-ordinates for this work are available on request from the director of the Cambridge Crystallographic Data Centre, University Chemical Laboratory, Lensfield Road, Cambridge CB2 lEW, UK.

(Received

in Japan

13 March

1984)