Structural elucidation and conformational analysis of germacrane-type diterpenoids from the brown alga pachydictyon coriaceum

Tetrahedron Letters,Vo1.27,No.23,pp Printed in Great Britain

0040-4039/86 $3.00 + .OO Pergamon Journals Ltd.

2639-2642,1986

STRUCTURAL ELUCIDATION AND CONFORMATIONAL ANALYSIS OF GERMACRANE-TYPE DITERPENOIDS FROM THE BROWN ALGA PACHYDICTYON CORIACEUM Midori Ishitsuka, Takenori Kusumi, Hiroshi Kakisawa*, t t Yoshiyuki Kawakami?, Yasushi Nagai , and Tadashi Sato Department of Chemistry, The University of Tsukuba, Sakura, Ibaraki 305, Japan t Tsukuba Research Laboraory, Eisai Company Co. Ltd., Ibaraki 300-26, Japan From the brown alga, Pachydictyon

Summary:

acetoxypachydiol

(41, 3-hydroxyacetyldilophol

ed, and the stereochemical

Natural

products

sesquiterpenoids

coriaceum,

features

possessing

three new

(21, and dilophol

'germacrane-type' acetate

of them as well as obscuronatin

(z),

have been isolat-

(13) have been elucidated. -

a cyclodecaneframework are frequently found as germacrane 1 On the contrary, diterpenoids having a ten-membered

in terrestrial

plants.

ring are much rarer, and it is only ten years ago that the first germacrane-type was isolated

dilophol,* membered

of the brown alga, Pachydictyon

type diterpenes structural

together

elucidaton

diterpene,

Since then, several other diterpenoids having a ten3-6 In the course of our study on the from marine resources.

from an alga.

ring have been obtained

constituents

diterpenes,

coriaceum,

with a known diterpene,

of the new compounds,

we have isolated three new qermacrane3 and this paper describes the

obscuronatin,

as well as the conformational

analysis

of these

compounds. Acetoxypachydiol obtained implies

(21, C22H3604

as a colorless the presence

acetylation

oil from the methanol

of acetoxy

(Ac20/Py),

-50 "C)

structure

infered

Fragments

suggest

additional

partial

in moiety

the acetoxymethyl

group.

(c 0.55, CHC13),

was

The IR spectrum (CC14) of P. coriaceum. -1 (3300-3600 cm ) groups. On

) and hydroxy

(lH-NMR), indicating

that two hy-

at m/z 109 and 69, and the lH-NMR siqnals depicted in 7 of the side chain 1. Decoupling works (400 MHz;

structures

2 indicates

-2 and -3.

are found in Lto

2.

The downfield

the cis relationship

Other three carbons

must be two CH *'s and one CH, because and l3 C-NMR)

[aID -76.4O

the existence

of the olefin proton

?H

extract -1

(1750 and 1240 cm

two acetyl groups were incorporated

droxy groups were present. the partial

(m/z for M+, 364.248),

and five protons

all of five methyl Consideration

2639

between which

(6

6.10) chemical shift

this olefin proton are not discussed

and above

groups that exist in acetoxypachydiol

of these facts and biogenesis

of diterpenes

2640

126.3

39.0

J values J

(-5O'C) of protons

2a- 28

J 2a- 1 J 2f3- 1 J2a-3 J 2B_ 3 JZOcP2OB J5_6 21.2.171.2

4#

J6_7

= 13.0 Hz 0 Hz = = 11.4 Hz = =

9.2 Hz 4.8 Hz

= 12.1 Hz =

9.9 Hz

=

0 Hz

led to the gross structure 4 (without stereochemistry) is located

on C-8 and C-9.

appear as broad which

or its isomer in which the qlycol moiety 1 1n the 400 MHZ H-NMR spectrum measured at 27'C, several protons

signals,

indicating

invert in a moderate

that acetoxypachydiol takes two or more conformations, 8 time scale. Interestingly, when the spectrum was

rate onanNMR

taken at -50°C, only one set of signals were observed. Similar phenomena were observed in the 13 C-NMR spectra; while the spectrum measured at 27°C (100 MHz) showed several broad signals (Fig. 1-A) and the number formula, suggest

the spectrum

of carbon

recorded

that acetoxypachydiol

minor conformer(s), the NMR spectra -5O'C provided constants

(Fig. 1-B) exhibited

takes a major

whose population

are supposed

constants

as the temperature

Double

resonance

of the protons

only when the conformation as seen in 6 or -7.

from the molecular

22 sharp signals.

(possibly >98%) conformation

increases

at that low temperature. the spin coupling

are interpretable

substituents

signals was less than the one expected

at -50°C

rises,

experiments

These facts

at -5O"C,

and the

is not observable

in

(400 MHz1 performed

at

(see structure

and relative

4). The coupling configurations of the

In order to differentiate

the two, NOR experi-

2641

;

AcO HO

(1;

BR,9a-dial

ments were carried observed

between

inGead

of 5,6-dial) but, unexpectedly,

out at -50°C using a 400 MHz spectrometer,

any pairs of protons

no NOR was

On the other hand,

by this high field spectrometer.

when a 250 MHz instrument was used, small but distinct NOES between several pairs of protons 9 These findings (depioted in 6) confirmed the structure and stereochemistry of were observed. acetoxypachydiol exactly

to be a.

MM2 calculations

showed that the most stable conformation

the same as 5, and free energy difference

-8 was ca. 1 kcal.

The dibenzoate

As -9.8; Xext 222 nm, AE +9.8), 10 determined as depicted in $_. Acetoxypachydiol

(3

-5 exhibited

and, hence,

between

negative

the absolute

is the first example

6 and the next favorable -

splitted

Cotton

effects

configuration

of diterpene

was conformation

(Xext 237 nm,

of acetoxypachydiol

that possesses

was

a 1,4_cyclodecadiene

skeleton. 3-Hydroxyacetyldilophol

(z), C22H3603,

[aID

-7.2O

(c 0.64, CHC13),

IR (CHC13) 3600, 1730,

1240 cm -l, MS m/z 348 CM+) , 306, 288, 270, 177, 159, 109, 69 (base), exhibited trum very similar with that of 3-acetoxyacetyldilophol (1) only one acetyl moved up to 6 4.36 assigned

signal was found in 2 and

(2) the chemical

and the structure

the 'H-NMR spec-

differences

shift of 3-H in g

(t, J = 3 Hz) in 2. on the basis of these properties,

for 3-hydroxyacetyldilophol,

-10 by acetylation.

(1O).6 -

Noticiable

was confirmed

.were that

(6 %5.0)

the structure

by conversion

2 was

of 2 into

2642

From a less polar fraction, dilophol acetate (111, [al, -30.9' (c 0.57, CHC13), IR (CHC131 -1 , was isolated. Hydrolysis (KOH/MeOH) of dilophol acetate produced dilophol

1730, 1240 cm WD

@jr2

-26.1°

(c 0.44, CHC13).

It is noteworthy

with silica gel

(Merck, Kieselgel

compoundonstanding ture for 24 hr. CHC13),

The product

by comparison

has been recently

These

signals.

indicate

and observation

The conformation

the protons

[1,51 shift of the acetoxy

as shown in -14.

acetate

Experiments 13

(11) is reasonably -

of the acetoxy

as

(l-H, 26-H, 5-H, using a para-

-14.

group to C-4 followed

removal

in contrast

was determined

of the key protons

the conformation

(13) from dilophol -

to C-4 with concomitant

interpreted

by hydrolysis,

by

or (ii)

group.

We are grateful to Dr. H. Yamamoto for high resolution mass spectra.

Acknowledgment: 1.

N. H. Fischer,

2.

V, Amico,

Products",

E. J. Oliver,

and H. D. Fischer,

Vol. 38, pp 47, Springer-Verlag, G. Oriente,

M. Piatteli,

3.

Y. Kashman,

4.

H. H. Sun, W. Fenical,

5,

R. Kazlauskas,

6.

N. Enoki,

H. Shirahama,

Chemistry

Lett.,

"Progress

in the Chemistry

of Natural

Wien New York, 1979.

C. Tringali,

E. Fattorusso,

S. Magno,

L. Mayol,

1976, 1024.

J. Chem. Sot. Chem, s,, I--A. Groweiss,

M. Ishitsuka,

J. Org. Chem., 1979, 5, 3814. --J. Org. Chem., 1979, 44, 1354. --P. T. Murphy, R. J. Wells, J. F. Blount, Tetrahedron A. Furusaki,

K. Suehiro,

Lett.,

1978, 4155.

E. Osawa, R. Ishida, T. Matsumoto,

1984, 459.

T. Kusumi, H. Kakisawa,

Y. Kawakami,

Y. Nagai, T. Sato, --J. Org. Chem.,

1983,

1937.

8.

K. Tori, I. Horibe,

H. Minato,

9.

At low temperature,

molecular

relation

time

of observation troscopy

Tetrahedron

motion becomes

Under these conditions,

(rd.

system)

[small Wo;

K. Takeda,

is large enough

10.

T. Yoshida,

M. Uchida,

11.

M. Kodama,

K. Okumura,

12.

Chiloptical

properties

J. Nobuhara,

(private communication A6 values (3&H),

Y. Kobayashi,

nificant

shifts. in

Japan

T. Tsunoda,

more the temperature

S. I&,

in cor-

(frequency

s.,

spec-

[larger Tc;

1976, 3717.

Tetrahedron

1984, -25, 5781.

g.,

from a soft coral Xenia obscuronata

are not known

from Prof. Y. Kashman).

(6-H), 1.85

(Received

in increase

Use of a low frequency

(tio~c)' = 1.

T. Okuda, Tetrahedron

of obscuronatin

(ppm, CDC13) on addition

2.46

slow , which will result

(WoTc)* < 1, +NOE] or lowering solve such problem.

1971, 4355.

w.,

NOE will become very small if WO

to make

(wo-rc)2 > 1, -NOEl would

13.

(c 0.49,

(22.5 MHz at 27'C) exhibited

of obscuronatin

patterns

[Eu[fodj31 also supported

of obscuronatin

(i) intramolecular

48,

[cl1 D -1120

takes one stable conformation

of the spin coupling

of NOES between

shift reagent

attack of water

Also the l3 C-NMR spectrum

that obscuronatin

diterpenes.

in 14, by analysis

Formation

7.

(G),3

the absolute

with other germacrane-type

magnetic

as obscuronatin

into a

at room tempera-

properties. The relative stereochemistry of obscuronatin 11 by synthesis, and since the absolute configuration of dilophol

confirmed

the well-defined

sharp signals.

6-H)

changed

configuration of obscuronatin in the present alga was 12 as in -13 by the above transformation. The 400 MHz lH-NMR spectrum (27OC) of -13

determined

depicted

acetate

60, Art. 7734, CH2C12)

of the spectral

(12) has been established,6 -

reveals

was characterized

that dilophol

of 1.4 molar equivalent

(2R-H), 1.55

8 February

(5-H), 1.11

1986)

(1-H).

of Eu(fod13: Other signals

2.82

(4-Me), 2.55

did not show sig-