Synthesis of macrocyclic terpenoids by intramolecular cyclization VI. Synthesis of 3Z-cembrene A and cembrenene

0040-4039/81/434275-02$02.00/O 01981 Pergamon Press Ltd.

Tetrahedron Letters, Vo1.22, N0.43, pp 4275 - 4276, 1981 Printed in Great Britain

SYNTHESIS

OF

MACROCYCLIC

TERPENOIDS

SYNTHESIS

OF

Kazuaki

BY

3Z-CEMBRENE

Shimada,

Department

Two

14-membered

coral,

respectively,

Abstract. and a soft

geranyl

phenyl

We

of

nephthenol isolated

the

phenyl

started

cyclization

acyclic

one of

the

1)

A

since

reaction

phenyl

secured

observation

with

Li/EtNH2

occurred with

of 5 with

very

those For

SOC12 However,

or

of the

with

Sh8

Tohoku

University

lt6*

Japan

A and

by the

cembrenene,

anion-induced

Na

6)

in

selectively natural

only

NOE

isolated

cyclization

give

was not presence The

besides

alcohol

of

minor

the

from of

a

geranyl-

this

case.

temperature

observed

The

thin-layer

partly

(ca.

(8 1.58

obtained

reported

z

overlapped

5%)

yield

1) .

yield)

whose

PMR

of

tetraenol

in

(3

.

the

.

the

in z

(6 5.47 (8)

and CMR

was

ppm).

5)

in 53%

on desulfurization

Dehydration

major

column

BZ-Geometry H3

similar

chromatography with

3Z-nephthenol

13%

previously

.4)

by repeated 5)

ppm) and

yielded in

A

Cubitermes

9

bond

was separated

isomer

of

14,15-oxidogeranylgeranyl

product its

(93%

of

synthesis

soldier,

Sinularia

spot

at room

a tetraene

coral,

the

anion-induced

3Z-cembrene

termite

a small

C4-methyl

2 5)

soft

of

for

are

the

PE-double

in

between

products

the

of

cyclization

noted

& was also

objects

grand

from

of

fj, (62%)

to the

of h

of 8_ by SOC12

spectra

are identical

A.

cembrenene

SOC12

the

THF

addition

al.

application

previously

synthetic

frontal

isomerization 2)

(11%)

t-BuOH

The

et

by the

developed

anion-induced

(6)‘).

to give

to yield with

the

. the

Hayashi,

sulfide

sulfide

The

to

of

of

exhibited

3Z-cembrene

synthesis

dehydration

by

cembrenoids

we have 2)

2 from

geometrical

!, (12%).

/EtOH

POC13,

of

method

with

phenyl

alumina

natural

and hedycaryol

@,) found

the

using

together

and

3Z-cembrene

synthesized

two

the

together

product

nephthenyl

Desulfurization

1)

re-examination

chromatography

yield

(2)

oxidofarnesyl

by the

of

precursor,

et al.

the 6)

of

crude

were

synthesis

and cembrenene

sulfide

the

the

(J.,), cembrene

We

of

herein

by Meinwald

umbraus3),

diterpenes,

VI.

CEMBRENENE

Kodama

of Chemistry, 980,

CYCLIZATION

sulfide.

describe

cyclization

A AND

Mitsuaki

Sendai

termite

INTRAMOLECULAR

(A),

a complex of

the

dehydration inseparable triene-dial

the

mixture ill,

4275

in

prepared

which from

2

7) the

was attempted pentaene

6 by the

way

first,

using

l,O is predominant. of

C2,3lsigmatropic

42%

z:

5

2

R=SPh

&:R=H rearrangement

of

pentaene

5) 4_

and

spectra

PMR

the

corresponding

was separated are

7) ,

sulfoxide

afforded

a mixture

in 42%

yield

by chromatography

with

those

of

identical

authentic

of

using

hydrocarbons

from

which

AgNO3-impregnated

the

SiO,.

Its

IR

cembrenene.

f$-+H 9

+OH

4 We

thank

cembrene

A,

Mr.

and

I.

Miura,

Dr.

Y.

Gtsuko

Uchio,

Pharmaceutical

Hiroshima

Co.,

University,

for

References

1)

M.

Kodama,

2)

b,

3)

D.F.

4)

Y.

Y.

Matsuki

and

ib&l.,

1121

(1976).

Wiemer,

J.

Meinwald,

Uchio,

H.

Nabeya,

S.

lt8,

Tetrahedron

G. D.

M.

Prestwich

Nakayama,

S.

Ltd.,

for

the

spectra

and

I.

spectral

of

identification

authentic

of

3z-

cembrenene.

Notes

Letters -I

and

the

3065

Miura,

(1975).

J.

Hayashi

and

T.

v 3460

cm-‘,

6

4.45

(lH,

m.

Hase,

44 =,

Cb., Tetrahedron

3950

(1979).

Letters,

2,

1689

(1981).

5) i’;

colorless

1.54

(3H,

(lH,

d,

6

30.8

(t),

(s),

133.2

(M+),

1.58

(3H,

(s),

133

(3H,

br.s),

J=16,

9),

36.0

v

isomerization

Yamada

and

M.

Kodama, in

K.

S.

15.5 (t), (5).

has been lt6,

(3H, 6.18

observed

Tetrahedron

9 July

and

5.

1961)

15.7

m), (q),

18.7

111.0

reported

data3)

1635, br.s), (lH,

965, 4.70

d,

m),

22.4

seems

5.03

(d),

are

3450

6

(CC14)

(lH,

24.7

m), (tx2),

125. 1 (d),

identical

to contain

890

cm -I,

6

(2H,

br.s),

4.80-5.25

with

(CDC13)

(3H,

(2H,

m),

(2H,

m),

1.53

(3H, (lH,

29.8

125.3

1.53

m), 5.47

5.07

those

some errors.

s),

cm-‘,

4.70-5.10

cm -I,

(q),

(3H,

(2H,

v

br.s),

885

125.0 data

4.65-5.20 (b. p.),

(3H,

1.34

s),

t,

(t), (d),

of

f?i

133. 1

authentic m/e

br.s), 5.24

270

1.61 (lH,

dd,

J=16).

by us in 3121

Tetrahedron

(t),

59

(lH, (q),

(3H,

J=lO),

1640,

4.74

and CMR

Letters -, lt6,

(lH,

(d),

1670,

1.80

4.64

1.62

v 2920,

PMR

3075,

J=8),

(b.p.),

d,

1.22

(M+),

J=1.5),

45.5

(CC$) br.s),

d,

68

(CC14)

m/e 290

These The

br.t,

oil,

(3H,

(q),

Miura.

Shimada

Japan

(M+),

40.2

148.7

1.52

br.s),

6

br.s),

colorless

I.

(3H, (lH,

s),

(3H,

(t),

(3H,

9

272

CMR

(s),

by Mr.

1.72 5.56

m/e

J=7),

1.59

(3H,

1.67

134.4

(b.p.),

H.

(Received

t,

(b.p.),

m).

1.14 3

31. 1 (t),

supplied

Similar

s),

59

br.s),

(5H,

J=7.5).

(lH,

(M+),

(3H,

(6H,‘br.s),

5.28

spectra

7)

t,

398

7.0-7.4

1.11

1.64

J=8),

6)

br.s),

(lH,

br.s),

m/e

J=lO),

(CC14,

5.35

oil,

sesquiterpene

series.

(1978). Letters -I

2763

(1977).

See,

M.

Kodama,

S.

Yokoo,