Synthesis of (+)-pachydictyol-A

Tetrahedron Letters No. 9, pp 851 - 854,

SYNTHESIS

1978.

OF

Universite

E. Greene

de Chimie

Scientifique

Press. Printed in Great Britain.

(+)-PACHYDICTYOL-A1

Andrew Laboratoire

Perwon

Organique,

et Medicale,

C.E.R.M.O.

38041 Grenoble,

France

(Received in UK 3 Ja,nuwr 1976; accepted for mblication 13 January 1978) The diterpene Pachydictyon

alcohol

elucidated

by X-ray

skeleton,

previously

exhibits highly

(z), isolated

pachydictyol-A

from the brown

marine

alga

was structurally and stereochemically (Dictyotaceae), crystallography and was shown to possess the hydroazulene

coriaceum

mild

unknown

antibiotic

stereoselective

among

activity synthesis

as the key step a reductive

pachydictyol-A

Interestingly,

the diterpenes2.

vs.Staphyloccus-- aureus. We wish to report a short, -of the natural material from (-)-a-santonin using

transposition

that

introduces

the correct

trans

ring

fusion. a-Santonin

rearrangement, hydroconverted 3,4,5 by photochemical 4 to the known crystalline dienone-lactone 4. This inter-

(1) is easily

and dehydration

lysis, mediate

not only possesses

addition

the correct

and the C-10 exocyclic considered

C-10

and sodium

in 55% yield

(c, 1.7, CHC13)

; I.R. v(film)

(br. s.,

1.15 ppm

l-H),

4.82

(d, J=6 Hz,

The trans results

ring

obtained

ions smoothly

[mp

for the latter.

-10 must

as was

117-118' cis-fused

have

4.27

on silica 1640,

gel [[a]:'

895 cm-l

(t, J=9 Hz,

l-H),

; [ali product

Oxidation

(Se02

1.88

6(CC14)

(s, 3-H),

at by analogy

were

quite

the

condit-

replaces

the

that was clearly 24 66-67" ; [aID = +8'

similar

to those

; Jones)

of -10 gave back 2, albeit in product5, strongly suggesting that

the two is the stereochemistry 10 and thus be -trans-fused . 851

with

the aforementioned

(l-a, 5-a H's) [mp spectra

the cis-fused

between

5-6 hydrogen

= +1.8"'

; N.M.R.

compound

the IR and NMR

the case with

difference

1775,

(M+)]. 9. assignment in 2 was arrived

(c, 1.7, CHC13)l 5 although

low yield

3040,

-10 (2, where <_$J = -35O (c, 1.7, CHC13)]

from the known

methyl-

with E-toluenesulfonylhydra3 the A -olefin 2, homogeneous

of 2 under

different

in cleanly

exocyclic

a crystalline

methylene)

the only

produced

purification

3080,

difficulty

was

2 sequentially

acetate

after

general

centers

last feature

enone 2. Treatment

exocyclic

reported

ketone

This

; m/e 232

fusion

using

in place.

to the corresponding

(br. s., 2-H),

3-H)

afforded

already

alcohols

of the conjugated

catecholborane

by VPC and TLC8,

5.33

unit

but in

of pachydictyol-A

at 3 of the 4 asymmetric

due to the otherwise

such tertiary

Treatment7

framework

stereochemistry

methylene

to be important

transforming 6 enes .

zine,

the general

absolute

at C-5,

i.e. compound

No. 9

852

0

0

Q3 ’

1. hv,AcOH

+-*2.

b

b

TsNHNH2;

a

0

KOH 3. SOCl2

0

O:H. 9 O6 NaOAce3H20

*13

0

1

1. LiAl

l

2

R=CH3,

R’=OAc

3

R=CH3,R’=OH

4

R,R’=CH2

f-id 1. H2Cr04

2. TsCl;TMSCI

b

b

2. LiAIHd C5H7Cu;

H+ 2

R=H,R’=OH

1

R=TMS,R’=OTs

fi

R=H;R’=

Pachydictyol

y

-A

No. 9

853

After could

considerable

be effectively

of I gave excess

study, carried

(TMSC~).

hydrofuran

The

resulting

followed

30-40s

by brief

overall

yield

I.R.

v(film)

5.00

(t, J=6 Hz,

3080,

0.83

ppm

3040,

(d, J=7 Hz,

stereoselective in ether

material

(cyclohexane) ethane

using

with

to afford 30

[[ alD

indistinguishable

mp

; N.M.R.

885 cm-l

excess

3.86

hydride

2

reduction

first

with

chlorotrimethylfree of tetra-

to a coupling

reaction with 11 in ether , which was

1-pentynylcopper

to afford 30 2 [[ aJD = +67“

6-&-pachydictyol-A

(8-1 in

(c, 1.7, cyclohexane) 6(CC14)

5.36

(br. s.,

(m, l-H), -ca.

1.7

; l-H),

(2s, 9-H),

CM+)].

pachydictyol-A, chromic

the ketone

acid-ether12

derived

from alcohol

underwent

8

a remarkably

(ca. 90% 2 and 10% 8) with lithium aluminum hydride after purification on silica gel (+)-pachydictyol-A = +98'

(c, 0.8,

; a-naphthylurethane

derivative

and

of lactone

in pyridine

I, essentially

subjected

(br. s., 2-H),

aqueous

aluminum

at -30'

to acid

; m/e 288

reduction

at -77'

(2). This

1635,

3-H)

As we had observed (or 2) by oxidation

chloride

4.58

Lithium

tosylate

immediately

exposure

"prenylation"

(TsCl) and then with

from lactone

l-H),

that

treated

primary

was

3-methyl-2-butenylmagnesium then

was

chloride

side products,

found

out as follows.

diol 5, as a gum, which

E-toluenesulfonyl

silane

it was

114-115'1

cyclohexane),

derivative

was

from an authentic

mp

114-115',

chromatographically sample

lit.2

[a13’ D

lit.2

= +106'=

a-naphthylur-

and spectroscopically

of the natural

product.

Acknowledgement The author interest J.J.

is most

in this work,

Sims,

L. Minale,

grateful

to Prof.

to Dr. Luu Bang and E. Fattorusso

P. Crabbe

for a gift

and Dr. J.L.

Luche

of cr-santonin,and

for samples

for their

to Profs.

of pachydictyol-A.

854

No. 9

References Contribution 1. see 2.

no24

from the Laboratorre

: J.L. Luche,

D.R. Hlrschfeld, Sims,

J. Amer.

Magno,

Chem.

L. Mayol,

G.H.Y.

Sot., E,

Chem.

C. Tringali,

Lin,

4049

C. Santacroce, J.C.S.

Organique,

CERMO.

For no23

for publrcatron.

W. Fenical,

and C. Tringali, Piattelli,

submitted

de Chimre

R.M. Wing,

P. Radlick,

D. Sica, Co*.,

V. Amico,

575

E. Fattorusso,

(1976)

G. Oriente,

; V. Amico,

S. Magno,

and J.J.

: E. Fattorusso,

(1973). See also

S.

M. Piattelli,

G. Oriente,

and L. Mayol,

ibid.,

M. 1024

(1976). 3.

D. Arigoni,

H. Bosshard,

Helv.

Acta.,

Chim.

4.

D.H.R.

5.

E.H. White,

6.

See,

Barton,

180,

1732

P. de Mayo,

S. Eguchl

for example

Corbella,

459

z,

: F. Shafizadeh

and N.R.

G. Jommi,

W.F. Huffman,

J. Chem.

Tetrahedron,

En.

Sot., 25,

Bhadane,

J. Chem.,

F. Orsini,

; K.J. Robertson

(1974)

and L.J. Krebaum,

(1957).

and J.N. Marx,

P. Gariboldi,

J.A. Marshall,

G. Biichi, 0. Jejer,

and M. Shafig,

; E. Piers and K.F. Cheng,

(1972)

try,

H. Bruderer,

Ruth,

(1957).

(1969).

J. Org.

Chem.,

48, 2234

(1970)

and G. Ferrari,

and W. Fenical,

and J.A.

929

2099

J. Amer.

37,

3168

; A.

Phytochemis-

ibid.,

16,

1071

Chem.

Sot.,

84,

(1977) 4691

(1972). 7.

G.W. Kabalka,

512 8.

D.T.C.

further Proton See, 10.

of 2 to potassium

indication

for example,

The stereoselective

tions

in view

of 2 afford

however,

12.

Baker, Jr.,

Jr., J. Org.

and G.W. Neal,

reference

well

Chem.,

41,

J. Org. -

afforded

separated

574

Chem.,

42,

of 2 from 4 and s

exclusiveiy with

7210

(1972).

is rather

unreliable.

from 2 at first

and K.T.

and certain

the @-s--fused system.

the proposed R. Lorne,

; E.J. Corey

C.P. Garg,

of 2

thus giving

5.

formation

nearly

a mixture

on TLC,

of this compound.

of the fact that hydrogenation5

are consistent

H.C. Brown,

in t-butanol

were

of the C-5 stereochemistry

F. Derguini-Boumechal, (1977)

which

of the homogeneity

Cf., a.,

1181

f-butoxide

epimer,

NMR determination

surprising

11.

and J.D.

J.D. Baker,

(1977).

Exposure

and its C-11 methyl

9.

Yang,

; G.W. Kabalka,

(1976)

reaction

These

Liu, J- Org.

J. Amer.

Chem.,

results,

mechanism7.

and G. Linstrumelle,

and D.J. Beames,

appears

1,4 -reduc-

36,

Tetrahedron Chem.

387

Sot.,

(1971).

94,

a

;