Structure of the further norditerpenoids of Podocarpus macrophyllus. Inumakilactone a glucoside, a plant growth inhibitor and inumakilactone E

33,

TetrahedronLetter8No.

STRUCTURE

OF

THE

INUMAKILACTONE

3385

PP

FURTHER

-

1972.

GROWTH

Hayashi

and Hi&hi

of Chemistry,

Tokyo

Yuh Bristol

Research

(Received

in

Podocarpus are potent

compounds of this macrophyllus

D.

communication structures

(Ill)

verified

when

calcd.

490.184,

nagilactone only two

of plant

Don,

inumakilactone

together with

doublets

I with

Eritiill.

INUMAKILACTONE

E

Otsuka,

Tokyo

Ching IIK

Sendai,

South

Road,

determination

Taipei,

Taiwan

for publioation10 July 1972)

cells

A (la)

Japan

Hsl

(3,5,6).

E (7) and inumakilactone

lactones We have

A glucoside,

and nagilactones

of these

1685,

m.p. 1623 and

8400 and 3ZOO cm”];

of three

acetic

with

of I, C,oH&,

vmax (KBr),

(KBr),

hydroxyl

anhydride

no hydroxyl

A diacetate

(%)

University,

and bisnor-diterpenoid

inumakilactone

the structure

spectm

presence

in the signals

with

&eat

(l-S),

some of which

isolated

two

more new

from the stem of

C (&I)

Podocarpus

and F (8).

new compaunds to which

The

present

we assigned

respectively.

and U.V.

The

in

and mitosis

groups [vmox

(2a).

reoeived

of expansion type,

AND

University,

Chung

nor-

J)O nm (e 5608);

hydroxyl

June 1972;

in

Kakisawu’

Pan Chen and Hong-Yen

to produce

deals

i.r.

30

Tohoku

of Taiwan,

Printed

It8

is known

I and VII,

The (EtOH),

Jopen

species

inhibitors

Institute

INHIBITOR

Kyoiku

Sh8 of Chemistry,

Preen.

OF PODOCARPUS MKROPHYLLUS.

A PLANT

Teruo

Department

Per-

NORDITERPENOIDS

A GLUCOSIDE,

Department

33%

(IV) (I&r),

revealing

due to the side in the spectra

groups

The

chains:

of derivatives

1535 cni’],

very

similar

afforded

n.m.r.

their

a I-lactone spectml

signals III,

suggested

the triacetate

are displaced

3385

of

resemblance. of the

[vmax

properties

spectrum (TABLE)

structuml

fvbthyl of

show the presence

in the molecule,

and pyridine

group.

220-22S”,

isopropyl

of an a-pyrone (KBr),

1770 cn?]

II

and

to those of nagilactone

by the molecular

(II),

[hmax

GHS80T0,

is very

Significant group,

in the spectrum

formula

M’

similar

with

differences which of

A

always

was

490.191, that

of

are seen appear as

II by a three-proton

doublet

at 6 1. .2!i and a two-proton

CH2-OAc

is\ evident.

presence

of a hydroxyl

to inumakilactone

3450,

hydroxyl,

large

group at C,

A glucoside

3350,

f-lactone

1780,

1710

chromatogmphy)

n. m. r.

and the

obtained

analyses

was deduced

from

Thence

6 4.15. (A6

1.42

From these

in I.

(VII), and

also

C24H3,0, 1640 co?;

M’

736,

hydrochloride

the

ppm) of l-l,,

physical

presence

of the

group CH3-$H-

upon acetylation

evidences

from the

n. m.r.

A diacetate

in addition

to the signals

Xmax (EtOH),

the

indicates

structure

IX,

spectml major

VII

hydrolysis

C,BH2,0BCl,

has the

with

m.p.

was a glucoside

analysis.

Although

difference

is seen

of glucose

group,

gave

the

I wets assigned

5%-HCI,

the in the

suggesting

revealing

glucose

which

These

of V.

spectral the

on acetylation

254~255’,

(V) by the same reaction. VII

following

222 nm (c 9500),

groupings.

and on mild

that

(VI),

m. p. 296-200~

3,

Glactone

inumakilactoneA

(see TABLE) revealed

of inumakilactone (TABLE),

shift

and a, B-unsatumted 146:

compcund

up-field

at

E.

lnumakilactone v (KBr),

The

multiplet

ws

chemical

The location spectrum

of VIII

chemical

glucosidyl

shifts

at C,5.

the

properties: presence

pentaacetate

(identified identical

by paper with

evidences of the

of yS, The

similar Met6

large

RO I

R=H

III

R=H

V

R=H

II

R=Ac

IV

R=Ac

VI

R=Ac

VII

R=H

VIII

R=Ac

X=CI

X

X=Br

Xl

X=OH

residue to that and

H7

coupling

CH20R

IX

the

and &tailed

glucosidyl

is very

of

3381

No. 33

Comp. Solv.

Mel8 MeP ?6 (Me,,)

TABLE.

N.m.r.

II

IV

V

VII

CDC13

PY

PY

CDC13

Spectm of Pertinent

lnumakilactones and their Derivatives*’

VIII

IX

X

XI

CDC13

CDC13

Py

b

pr

VI

1.45

1.45

1.53

1.50

1.52

1.53

1.60

1.66

1.63

1.38

1.33

1.40

1.35

1.13

1.15

1.95

2.04

1.92

1.25d

1.2ld

1.56d

1.57d

1.4ld

1.33d

1.53d

1.57d

1.59d

(8.0)

(7.0) 1.24d

(6.5)

(6.0)

(6.3)

(6.0)

(6.0)

(6.0)

(6.5)

3.62d

3.62d

3.48*2

3. 46*2

4.95d

5.03d

(4.0)

(4.0)

(3.0)

(2.5)

(7.0) 5.05m

“1

“2

“3

“5 “6

“7

“11

5.10m

*3

*3

3.5ldd (4.0,6.0)

3.52dd (4.0,6.0)

3. 45*2

3.44*2

4.67dd (5.0,3.0)

4.75br

4. 65brf2

*3

*3

4.65d

4.65d

5.46m

5.45m

4. 31d

4.4Obr

4.4Obr

(6.0)

(6.0)

2.83d

(5.0)

1.87d

1.89d

2.13d

2.lOd

2.07d

2.73d

2.70d

(5.0)

(6.0)

(5.5)

(5.0)

(4.8)

(5.0)

(4.5)

(4.5)

(4.5)

5.05m

5.05dd (9.2,6.0)

5. 08*2

*4

4.86dd (4.8,l.J)

4.85dd (5.0,l.O)

5.33dd (4.5,l.S)

5.32dd (4.5,1.5)

5.3ldd (4.5,1.5)

6.25d (10.0)

6.35d

5.08*2

*4

3.99d

4,74d

5.15d

5.16d

(1.0)

(1.5)

(1.5)

5.90

5.83

(9.2)

“14 3.22m

“15

4. 65brf2

2.97sept

(1. J)

2. OOd

5.16d (1.5)

6.73

6.70

6.40

6.35

6.52

6.60

6.75

4.72d

4.52d (10.0)

4.78d

4.4Od

4.73d

4.73d

4.74d

(8.5)

(4.9)

(8.0)

(8.5)

(8.5)

(8.5)

4.13m

*3

4.06d,q (8.0,6.0)

4.35d,q (8.5,6.0)

4.4Obr

4.4Obr

(7.0)

4.974 q (4.9,6.3)

4.15m

“17 cH3co

*l

2.12 2.14

2.00 2.16 2. P

2.06 2. 12

2.00,2.02 2.03,2.10 2.15

Expressed in ppm from TM. Numbers without signal multiplicity Numbers in parentheses ¬e coupling constants.

*2 Chemical

shifts are approximate

because of

*3 Unassignable. *4 The signal overlaps with that of water.

overlapping.

(d, t,m,

etc.)

are singlets.

h

3388

constant

(J=8,

at 4.64

anomeric

hydrogen.

a potent

inhibitor

Thus,

fact

only

original

mentioned

above

that

the

X and Xl, shift

by the

presence

magnitude

into

as well

of halogen

of J2,8 (=5

Hz)

H z ) reveals

H,

+dihydroxy

structure

cells

is only

as of Me28 atoms at Cl,

interpretable

n. m.r. with

the

the

axial

VII

nature

of the

was shown to be

(9). comparisons lN-H2S04

in these hence

at C2 and C8,

discloses

A 15$-glucoside.

on the

ring

when

data

can be reconciled

ring

A in a twisted

of its n.m.r. treatments,

compounds

H8 should

when

boat

be tmns

the

the As

(H2=8,

the the

HB=a).

conformation,

of an epoxide

compounds

conformation

Since

baat

opening

with

significantlyj

of H,.

A of a twisted a tmns

dato

respectively.

vary

the assignment

H2 and

by the

to be a (axial)-orientation

Thus the

considemtian.

le-halo-2a,

of H,,

of Vill

from V by HBr and

in V should be retained

of JT,2(=2.5-8

taken

of plant

was determined

prepared

chemical

reside

as inumakilactone

of IX

explicable

the

was concluded ond division

configurations

While

of glucose

expansion

derivatives

seen in TABLE,

VII

) of H,

of the

The structure corresponding

ppm in CDCIB

33

IX and

as shown

is

X have

in A (10).

References l

To whom all

1) a.

S. lt8,

(1968). 2) a.

Y.

M.

3) a.

Y.

lt8,

Hayashi, M.

6) M.N.

M.

8) Privote

Kodamo,

H.

Y.

Hayashi,

Horn,

J.M.

lmamum and 0.

Jetmhedron

S. Takahashi,

Shimado,

Letters,

Chemistry

1862

(1971).

M.

Suna~wa,

D.H.S.

Horn,

previously

Publication, communication

9) The biological activity Chemistry, C.S. I.R.O.

&

M. S. lt8,

Koreeda M.

and K.

2871

Letters,

(1968).

Comm.,

&hem.

Sasse, Agr.

Comm., Biol.

OS inumakilactone

D (S. It8 and M.

Kodama,

with

(5).

Dr.

Y.

Hoyashi,

Osaka

City

3

S. IM, 2951

M.

’

(lW9).

b. M. N.

253 (1972). Bmsil Cignc,

855 (1971).

Chem.,

1968)

from

b. Ibid.,

An. Acad. 433 (1972).

Nankodo,

ponalactone

2065 91 (1971).

170 (1970).

Experientia,

designated

is identical

Comm.,

849 (1972).

Chem.

c. @,

Nakanishi,

Kodama and J.M.

T&&gdrmqrq,

aem.

H. Ono and T. Sakan,

Sasse and D. Adamson,

Sasse, jb&,

Honda,

Honma and T. Takahashi,

H. Ona and T. Sakan,

K. Hirotsu and A.

D.H.S.

H.

L., K.S. Brown, Jr., T. Nishida, L. J. Durham and A.M. Duffield, M. Silva, M. Haeneisen and P. G. Sammes, Phvtochemistry, L

Galbmith,

TO) lnumakilactone the same part

be addressed.

T. Takahashi,

M.

H. Honma,

T. Sakan,

Kodamo,

7) The compound Special

Sunagawo,

D. H. S. Horn and J.M.

4) W.E.Siinchez s 77 (197). 5) S. lt8,

should

Sunagawa,

S. Takahashi,

Galbmith,

Galbmith,

M.

M.

Sunagawa,

Hayashi,

M. N.

correspondences

Kadamo,

b. 5.

Kodama, c.

the

in press.

Kagaku

no Ryoiki,

University.

test was carried out by courtesy of Dr. M. N. Galbraith ot the Division of Applied to whom wr sincere thanks are due. For method, see (b) and (6).

C (2) also undergoes the epoxide ring cleavage with acids. N.m.r. analysis mvealed structure A in the probcts. M. Sunagawa, M.Sc. Thesis, Tohoku University, 1968.