Tetrahedron Vol. 38, No. 17, pp.

2627 to 2633, 1982

Printed in Great Britain.

0040.-4020~82[172627.-07503.00~
19~2 Pergamon Press Ltd.

A NOVEL TOTAL

S Y N T H E S I S OF E L A E O C A R P U S A L K A L O I D S

H I R O T A K A OTOMASU,

N O R I Y U K I TAKATSU,

T O S H I O HONDA

and
T E T S U J I KAMETANI

Hoshi C o l l e g e of P h a r m a c y
Ebara 2-4-41, Shinagawa-ku, Tokyo 142, J a p a n

(Received in Japan 5 June 1982)

~ The novel synthesis of e l a e o c a r p u s alkaloids has
en a c n l e v e a e m p l o y i n g 1,3-dipolar c y c l o a d d i t i o n reaction as a
key step.

Elaeocarpus alkaloids,
kanine A(~), B(~)

the leaves of E l a e o c a r p u s

dipolar cycloaddition

such as elaeo-

and C(~),

isolated from

pyrrolin-l-oxide,

r e a c t i o n of A l-

w h i c h might serve as

a chemical e q u i v a l e n t of ornithine,

k a n i e n s i s by

with

Johns and his c o - w o r k e r s I , are known to

an a p p r o p r i a t e e i g h t - c a r b o n s d i p o l a r o p h i l e

possess

has been investigated.

a characteristic

lizidine ring system.

can be d e r i v e d

T h e s e alkaloids

from a p p r o p r i a t e c o n d e n s a -

tion of o r n i t h i n e
and a b i o s y n t h e t i c

alkaloids

has been shown 1

1,3-dipolar c y c l o a d d i t i o n

For this purpose,

i
H,,..

the 1,3-

who however has used A l-

ing m a t e r i a l s

have been i n t r o d u c e d

at the later stage.

'O

Scheme
2627

as start-

and the C 5 - C 7 carbons

HO

re-

action has o r i g i n a l l y been a c h i e v e d by

pyrrolin-l-oxide and p e n t - l - e n e

these

along with the above b i o s y n t h e -

In

Tufariello 5

I.

tic pathway.

many

p a p e r s 2-9 have appeared to date.

employing

scheme for the deri-

We have p l a n n e d to synthesize

W i t h regard to

the synthesis of these alkaloids,

fact, the synthesis of e l a e o k a n i n e C

and a C s - p o l y k e t i d e ,

v a t i o n of these alkaloids
in scheme

trans-indo-

2628

H. OTOMASUet al.
treated with n-butyraldehyde
sence of n-butyllithium
Our requisite

enone

which would be a substitute

ketide was prepared

with

of Cs-poly-

as follows.

i-oi tetrahydropyranyl

acetylenic

as a dipolarophile,

ether

Butyn-

(~) was

alcohol

in the pre-

to afford

(~), whose

lithium aluminum

hydride I0 in tetra-

hydrofuran

gave the trans-olefin

69 % yield

from ~.

OH

the

reduction

OH

(~) in

_.~~OTHP
OTHP
OTHP

OH

OTHP
Scheme
The trans-enone
treatment

(~) was obtained

of the alcohol

ganese dioxide
% yield.

reduction

be synthesized
(~)

investigated.

was then

mechanistic

be an appropriate
size elaeokanine
Thus,
~

the adduct

isoxazolidine
deprotection
1N

the trans-enone

of ~ with
to afford

ring,

in 9 1 %

yield,

of tetrahydropyranyl

hydrochloric
The ratio of ~ a

acid

of the
whose
ether

in t~trahydro-

alcohol

(~a

and

: 12b was deter-

and 3.97
H)],
those

(2/5H, dt, J = 6 and 8 Hz,

(3/5H, dt, J = 8 and 8 Hz,

and this ratio was consistent

reported 12

initially

3e-H)

Difficulties

encountered

37with

were

in the c o n v e r s i o n

mixtures,

treatment
salt

chloride

and

chloride

again

of ~

acetic

hydroxy ketone

with methanegave the

which without

lation was treated with

% aqueous

product.

in pyridine

(~),

from elaeokanine

The stereochemistry
ketone was assigned
of its spectral
~

suggested

the

in 50
B-

as a major product

a trace amount of elaeokanine

arising

iso-

zinc powder

acid to yield

(~)

alco-

product

and mesylation

in methylene

chloride

quaternary

and

A, probably

C by dehydration.

of the

to be ~

S-hydroxy
on the basis

data and the formation

that the epimerization

of

at

the C4-position

of the isoxaz~idine ( ~ b )

occurred

during

its conversion

as shown

in Scheme

mined to be 2 : 3 based o~ its NMR data

[6 4.06

of the primary

gave rise to the decomposed

stereoiso-

at the C3-position

furan gave the primary

~b).

would

followed by

with methanesulfonyl

Whereas,

to synthe-

cycloaddition

as inseparab%e

of ~

sulfonyl

Based on the

out in chloroform

(~)

meric mixtures

but complicated

the

C, stereoselectively.

1,3-dipolar

was carried

with

mesylation

oxi-

N-O

palladi-

hol afforded none of the desired

triethylamine

dipolarophile

reductive

selective

Al-pyrrolin-l-oxide

aspects,

attempted

(~) was

stereoselectively,
with

tO 4' e.g.

bond cleavage with Raney-nickel,

of ~ on

(~ and ~) could

cycloaddition

of ~

and zinc powder,

from ~.

Since the both enones

um-carbon

(~) with manganese

in 48 % yield

OTHP

in 70

sulfate II and subsequent

dation of the olefin

dioxide,

ether

the cis-enone

by catalytic

palladium

(~) with man-

in petroleum

Whereas

prepared

by

OTHP

In order

to confirm

the cis-enone
furnish
tection
1N

(~),

from ~ .
acid,

to

which was clear-

After

of tetrahydropyranyl

hydrochloric

14

this observation,

(~) was treated with ~

the adduct

ly different

into

4.

the deproether with

the resulting

A noveltomlsyn~esisofelaeocardusal~loids
primary

alcohol

(~)

was converted

to the

quaternary

salt with methanesulfonyl

chloride.

Reduction

powder
in 25.8

afforded
% yield,

~he authentic
trans-enone

(~) as above.

stereoselective

ketone

which was identical

sample obtained

zinc

sulfoxide

(~)

(~),

or with Jones reagent.

sion of ~

from the

of elaeokanine

was oxidi-

with dimethyl

and dicyclohexylcarbodiimide 13

with

Though the

synthesis

C has not been successful,

zed to the diketone

of the salt with

the B-hydroxy

2629

Since the conver-

to elaeokanine

B(~)

and C(~)

has already been reported,

this synthesis

constitutes

a formal total

synthesis

elaeokanine

alkaloids.

%Ms

OR

OTHP

HO

"~

OTHP
~

Scheme

R=THP

~ n

r--~

of

H. OTOMASUet al.

2630

H,,,
-H20

]"" ""

>

OH
3

~a

.L

.>
H

III
12b

19
Scheme

4
The

EXPERIMENTAL

organic

with
IR s p e c t r a
Hitachi

were

Grating

measured

infrared

with

a 215

aq

and concentrated
which

spectrophoto-

phases

saturated

was

were

combined,

sodium
to give

chromatographed

(400 g) e l u t i n g

with

on

CH2CI2-MeOH

~ as a c o l o r l e s s

oil

spectra

97.6

: IR

3430

spectrometer
an

using

internal

taken

with

on a J E O L

JNM-FXI00

tetramethylsilane

reference.
a JEOL

Mass

JMS-D300

spectra

%)

as

2960,

were

(3H,

spectrometer.

7 Hz),

(2H,
3-Octyne-l,5-diol
ether

(5).

butyn-l-ol
g,

74.6

l-tetrahydropyranyl

To a s t i r r e d

solution

tetrahydropyranyl

mmol)

of

ether

in t e t r a h y d r o f u r a n

(11.5

(50 ml)

was

added

a solution

of n - b u t y l l i t h i u m

(15

% w/v

in h e x a n e ;

57.3

at

-78C

over

stirring

for

(6.45

89.5

g,

resulting
for

1.5

phase

0.5

hr,

mmol)

mixture

Water
were

was

2 hr.

added

and

stirred

then

(50 ml)

then

of

89.5

was

added
The

extracted

with

ether

1),

4.64

- 3.93

(IH, m);

209,

137,

107,

C13H2203

: C,

68.99;

68.91;

H,

9.92

After

lithium
mmol)

the

and

(4).

the

aqueous

(2 x 30 ml).

tion

aluminum

(21.3

g,

for

4 hr at a m b i e n t

quenched

J = 2

3.42

- 3.65

227

H,

(m/e)
Calc

(IH,
(M + +

for

9.80.

Found:

C,

]-tetrahydropyranyl

(200 ml)

at r o o m

(4.28
was

addition

of
113

a solu-

in e t h e r

After

the

g,

added

temperature

nitrogen,

by the

suspension

94 mmol)

temperature.

of

,% 0.94
dt,

MS

hydride

ml)

atmosphere

(2H,

4.34

85.

: i)

(broad),

(2H, m),

To a s t i r r e d

in e t h e r
of

(19

%.

3(E)-Octene-l,5-diol

to w a r m

separated.

s),

3.69

gel

(16.5 g,

(CDCI 3)

2.51

(IH, br s),

ether

at - 7 8 C

allowed

m),

2.68

cm -I

NMR

mmol)

n-butyraldehyde
was

was

hr and w a s

to 0C.
phases

the p e r i o d

ml,

3-

1030;

t, J = 7 Hz),

and

br

2880,

(film)

oil,

silica

to give

obtained

dried,

a yellowish

m e t e r a n d w e r e c a l i b r a t e d w i t h the 1610
c m -I a b s o r p t i o n of p o l y s t y r e n e .
IH-NMR
were

washed

chloride,

(30

stirring
under

reaction

of w a t e r

an
was

(20 ml).

A novel~talsy~hesisofel~oc~dusalkMoids
The

insoluble

material

ed off and w a s h e d
The c o m b i n e d

filtrate

give a r e s i d u e ,
on s i l i c a
acetone

was evaporated

(500 g) e l u t i n g

(15.3 g, 7 1 . 1 % )

(broad),

2940,

(CDCI 3) 6 0.93

: IR

2870,

(3H, m),

w i t h C H 2 C I 2(film)

1030,

1.78

(IH, br s),

4.20

(5H, m),

5.67

(2H, m); MS

109,

I01,

10.93

H,

4.58

(IH, br m),

(m/e)

Calc

10.59.

211

3.30 -

5.30 -

(M+-OH),

for C 1 3 H 2 4 0 3

Found:

c m -I

970; N M R

(2H, dr, J = 6 a n d 6.5 Hz),

68.38;

to

~ as a c o l o r -

2.34

85.

filter-

(5 x 39 ml).

which was chromatographed

(19 : I) to a f f o r d

less oil
3445

gel

formed was

with ether

: C,

C, 68.59;

aq s o d i u m c h l o r i d e ,

dried,

r a t e d to give a r e s i d u e ,
j e c t e d to c o l u m n
gel

(100 g).

(2.76 g, 68.3
(broad),
6 0.94

and concent-

w h i c h w a s sub-

chromatography

%)

2955,

~ as a c o l o r l e s s
: IR

2870,

(film)

(3H, m),

3.24 - 3.63

(2H, m),

4.40

4.60

(CDCI 3)

2.10 - 2.80

(2H, m),

3.68 - 3.96

(IH, dt, J = 6.5 and 6.5

(IH, br m),

(m/e)

oil

c m -I 3450

1033; N M R

(3H, t, J = 7 Hz),

m); MS

on s i l i c a

Elution with CH2Cl2-acetone

(19 : i) a f f o r d e d

Hz),

127,

2631

211

5.16 - 5.69

(M+-OH),

127,

(2H,

109,

i01,

85.
Calc for C 1 3 H 2 4 0 3 : C, 68.38; H,
10.59.
Found: C, 68.09; H, 10.85 %.

%.
5-Oxo-3(Z)-Octen-l-ol t e t r a h y d r o p y r a n y l

5-Oxo-3(E)-octen-l-ol
ether

(~).

tetrahydropyran~l

To a s t i r r e d

manganese d i o x i d e

suspension

ether

(150 ml) w a s a d d e d 6
a n d the m i x t u r e

was

temperature

of an i n s o l u b l e

ration,

the f i l t r a t e

on s i l i c a

stirred

1 hr.

material

After
by f i l t -

was concentrated

to

which was chromatographed

gel e l u t i n g w i t h C H 2 C l 2 - a c e t o n e

(97 : 3) to y i e l d the e n o n e

(~).

The o x i d a t i o n

18.8 mmol)

with manganese

in p e t r o l e u m

(2.5 g, 10.9
further

for

removal

the r e s i d u e ,

of

(20.3 g) in p e t r o l e u m

mmol)

at a m b i e n t

ether

~ as a c o l o r -

out as d e s c r i b e d

NMR

(CDCI 3)

2.44

and 6.5 Hz),

2.52

3.41 - 3.64
4.59

and 16 Hz),
Hz); MS
Calc

6.84

(m/e)

(2H, m),

(IH, dt, J = 1.4

(IH, dt, J = 7 and

227

C, 68.61;

3.76 - 3.99

6.17

(M + + i),

for C 1 3 H 2 2 0 3

Found:

153,

: C, 68.99;
H,

10.04

3(Z)-Octene-l,5-diol
(~).

mmol),

H,

16

125,

(20 ml) w a s
under

mmol)

of ~

(400 mg)

shaken

9.80.

%.

4.59

6.03 - 6.34

(2H, m) ; M S

17.7

and pyridine
temperature

of h y d r o g e n .

of h y d r o g e n

had c e a s e d ,

(397 ml,

: C, 68.99;

the c a t a l y s t

The combined

filtrate

centrated

to the r e s i d u e ,

dissolved

in b e n z e n e

anic

layer was washed

potassium

125,

H,

(m/e)

85.

9.80.

(2H, m)

(IH, br m),

Calc

227

(M + +

for C 1 3 H 2 2 0 3

Found:

C, 68.84;

%.

1,3-Dipolar

cycloaddition

of ~ : Forma-

t i o n of the

isoxazolidine

(~).

toluene

hydrogen

with

sulfate

(15 ml) w a s r e f l u x e d

was

in a c u r r e n t

After evaporation

the r e s i d u e
gel

and A l - p y -

(0.84 g, 9.88 mmol)

in

at a m b i e n t

of n i t r o g e n

for

of the solvent,

was c h r o m a t o g r a p h e d

on s i l i c a

(100 g) e l u t i n g w i t h C H 2 C l 2 - a c e t o n e

(17 : 3) to a f f o r d
as s t e r e o i s o m e r i c

the

isoxazolidine

mixtures

(~)

at the C 3 - p o s i -

tion

(isoxazolidine

numbering)

(1.39 g,

17.7

91.0

%)

c m -I 2950,

2850,

filter-

1033;

(3 x

w a s con-

w h i c h was re-

(50 ml).

(I.Ii g, 4.90 mmol)

rrolin-l-oxide

A solu-

After

ed off and w a s w a s h e d w i t h b e n z e n e
10 ml).

153,

temperature

(4.0 g,

at a m b i e n t

an a t m o s p h e r e

an a b s o r p t i o n

(2H, ddd,

(2H, m),

tion of ~
85.

l-tetrahydropyranyl

A mixture

PdSO4~H20

2.93

3.71 - 3.94

3 hr.
ether

(3H, t, J = 7 Hz),

(2H, t, J = 7.5 Hz),

(2H, m),

(IH, br m),

6 0.93

3.39 - 3.61

H, 9.99

6.5

for ~ to g i v e ~ as a

J = 5, 6 and 6.5 Hz),

t, J = 7 Hz),

J = 1.4,

(40 g)

(150 ml) w a s c a r r i e d

(2H, t, J = 7 Hz),

i), 209,

(2H, dtt,

(4.30 g,

c o l o r l e s s oil (2.78 g, 70.2 %) : IR (film)

-i
cm
2950, 2875, 1693, 1620, 1032, 985;

less o i l (1.74 g, 70.2 %) : IR (film) c m -I

2950, 2875, 1680; N M R (CDCI3) 6 0.94 (3H,
2.51

ether

of ~

dioxide

The o r g -

saturated

aq

and s a t u r a t e d

Hz),

: IR

NMR
2.41

(CDCI 3) t 0.93

(3H, m),

3.31 - 3.65
4.43

(IH, dt,

(IH, br m) ; MS

(M+ + I),

(M+),

85.

310,

3.14

(3H, m),

8.5 Hz) , 4.56

311

1710,

(3H, t, J = 7

(2H, t, J = 7 Hz),

J = 6.5 Hz),
3.98

(film)

(2H, t,
3.73 -

J = 6 and

228,

(m/e)

312

152,

86,

2632

H. OToMAsuetal.

Deprotection
o__[f ~ .

o_~f t e t r a h y d r o p y r a n y l

To a s t i r r e d

mg,

1.61 mmol)

was

added

been

IN HCl

extracted
organic

(4.5 ml)

After

the

for

5 hr,

continued
basified

with

with
layer

to g i v e

subjected

to c o l u m n

MeOH

gel

cm -I

(CDCI3)

Hz),

(2H,

2.43
3.56

(2H,

(3/5H,

8 Hz),

dd,

(2/5H,

4.50

(IH,

dt,

86,

(3/5H,
dt,

143,

85; m / e

(~)
%)

3.16

1710,

(2H,

8 Hz),
dt,

3.71

J =
8

8 Hz),

- 3.40

(3H, m),

3.50

- 3.80

3.90

112,

for

(I).

tion

of the

isoxazolidine

(~).

tion

of

(2.50

rrolin-l-oxide
chloroform

and

14 hr.
the

(17

(I{88

then

After

gel

g,

was

heated

3.70
and

mmol)

mmol)

After

evaporation

residue

the

(3H,

- 4.20

2.30

4.54

(IH, m) ; MS

+ i) , 311,

3]0,

228,

nyl

15.

ether

was

to g i v e
gum

of

- 2.60

dt,

154,

86,

15

of

(2.00

g,

6.42

carried

out

(1.05

g,

71.6

%)

ether

mmol)

in t e t r a h y d r o f u r a n

alcohol

85.

tetrahydropyra-

(15 ml)

the

(M +

as d e s c r i b e d

with
(80

(film)

50

at

50C a n d

continued

for

The

ed to 0C,

moval

diluted

with

of the

ration,

filtrate

chloride,

the

column
g).

residue,

with

gum

(309 mg,

C H C I 3) cm -I

3420

2480,

1375;

3H,

1705,

2.54

(m/e)
124,

(2H,

14 w a s
160

2.80

$ 0.91

2.55

(IH,
(3H,

10 Hz) ; MS

167,

152,

140,

for C I 2 H 2 1 N O 2 ,
as

its

(from e t h a n o l ) ,

49.09;

49.00;

J = 7 and

crystallized

C,

2807,

- 3.30

(calc

: C,

as a

: IR

tq

- 161.5C

Found:

elution

with

elaeokanine

spectral
of

(2H,

(80

: 3)

H,

H,

5.49;

5.61;

N,

%.

Further
gave

(14)
%)

2933,

182,

211.1583

for C I 8 H 2 4 N 4 0 9

12.56

16.6

J = 5 and

(M+) , 194,

12.72.

gel
(17

t, J = 7 Hz),

I0 Hz),

m.p.

to

(CDCI3)

1.60

(IH, dt,

211

97; m / e

calc
N,

NMR

t, J = 7 Hz),

J = I0 and

to

silica

(broad),

aq

subjected

CH2CI2-MeOH

7-epielaeokanine

with

The org-

evaporated

was

on

re-

saturated

and

which

chromatography

Elution

extracted

with

and

by f i l t -

(3 x 40 ml).

dried

cool-

After

material

was

temper-

(30 ml)

N a 2 C O 3 to pH 9.

chloride

g,

was

was

with water

laye'r w a s w a s h e d

give

same

solution

insoluble

the

stirred
(8.63

stirring

1.5 hr at the

resulting

% aq a c e -

above

the

the

data

reported

were

CH2CI2-MeOH

(2 mg,

0.I

consistent

(17

: 3)

%), w h o s e
with

those

o n e I.

above

(3~6) as a y e l l o w i s h
: IR

into

zinc p o w d e r

picrate,

312

5 hr.

solvent,

To the

211.1573).

J = 6

(m/e)

of t e t r a h y d r o p y r a n y l

Deprotection

I N HCl
ml)

210,

(CDCI3)

allow-

for

dissolved

132 mmol)

(3.02 g,

temperature

of the

added

8.80

was

was

m) , 3.87

(film)

(2H, m),

(IH,

for

(44 ml)

solution

dd,

as a

(2.0 g,
chloride

(44 ml).

7 Hz),

: IR

NMR

3.48

(3H, m) , 4.42

Deprotection

%)

1033;

9 Hz),

of

on

(15)

90.4

(2H, m),

for

solvent,

CH2Cl2-acetone

t, J = 7 Hz),

3.15

reflux

addHct

(calc

and elaeokanine

12

at r o o m

was

afforded
for

(~4)
of

tic a c i d

colorless

of the

(2.5H,

(0.5 H, dt,

227.1537

and pyridine

stand

at a m b i e n t

of n i t r o g e n

under

with

Al-py -

ed to

in

chromatographed

eluting

: 3) to g i v e

0.93

22.1

stirred

c o l o r l e s s g u m (3.11 g,
-1
cm
2950, 2875, 1710,

(3H, m),

A soluand

evaporation

was

: Forma-

mmol)

in a c u r r e n t

residue

silica

Ii.0

(30 ml)

temperature
3 days

g,

4.50

m/e

methanesulfonyl

sodium
of ~

8.5 Hz);

A mixture

mmol),

anic

cycloaddition

(IH, m),

227.1520).

methylene

C I 2 H 2 1 N O 3, 2 2 7 . 1 5 2 0 ) .

1,3-Dipolar

- 4.20

basified

(m/e)

125,

(calc

(IH, br s),

2.80

ature.

J = 8 and

128,

227.1509

: IR

t, J = 7

8 Hz) ; MS

138,

t, J = 7.5 Hz),

2.91

26.4

2885,

J = 6 and

J = 6 and

154,

dt,

was

C H 2 C I 2-

74.0

(2/5H,

(3H,

1055;

(2H, m),

on

alcohol

J = 8 and

6 0.94

1710,

- 2.60

7-Epielaeokanine

con-

which

(3H,

3.76

3.97

4.06

(M+),

and

t, J = 7.5 Hz),

Hz),

110,

~ 0.94

2880,

2.40

CI2H21NO3,

satura-

2975,

(CDCI3)

2970,

The

with

(270 mg,

t, J = 6 Hz),

6 and

the

(broad),

1058;.NMR

227

Elution

NMR

J = 5.5 and

and

chromatography

gum

3410

with
dried,

(broad),

m),

solution

carbonate

residue,

(9 : i) a f f o r d e d

(film)

m),

the

(25 g).

as a y e l l o w i s h

had

(3 x I0 ml).

chloride,

centrated

at a m b i e n t

the

was washed

3390

(500

(7 ml)

stirring

sodium

ether

t e d aq s o d i u m

silica

ether

of 1~

in t e t r a h y d r o f u r a n

temperature.

was

solution

cm -I

The

conversion

version

of

of J~

into ~4.

(300 mg,

The

1.32 mmol)

conwas

A noveltotalsynthesisofelaeoc~dusalk~oids

2633

c a r r i e d out as above by m e s y l a t i o n with

Acknowledgements --

methanesulfonyl

Miss M. Shigetsuna,

mmol)

chloride

(455 mg,

3.97

and a subsequent reduction w i t h

zinc powder

(1.15 g, 17.6 mmol)

aq acetic acid
(72 mg,

(6.6 ml)

A. Kumazawa,

in 50 %

to afford

14

for spectral m e a s u r e m e n t s ,

sulfoxide

in b e n z e n e

(150 mg,

IN. K. Hart,

(5 ml) a n d d i m e t h y l -

(5 ml) c o n t a i n i n g p y r i d i n e

mg, 0.76 mmol)

and t r i f l u o r o a c e t i c

(60

acid

hexylcarbodiimide

(580 mg,

J. A. Lambert.n,
817

3N. J. Leonard,
J. Figueras,

ambient temperature

4620

was d i l u t e d w i t h w a t e r
Carbon tetrachloride

After

the residue

to pH ii.

73', 240

R. G. Lingard,

A. E. E. Theobald,
sj. j. T u f a r i e l l o

The com-

C. A. Meerholz,

w i t h water,

~T. Watanabe,

and e v a p o r a t e d to give

ibid., ~ ,

and M. Yamauchi,

c h r o m a t o g r a p h y on silica gel

(1980).

(9 : i) afforded

8H. F. S c h m i t t h e n n e r

the d i k e t o n e

2 %)

J. Org. Chem.

t, J = 7.5 Hz); MS

(CDCI 3) 6 0.92

(m/e)

164, 152,

209

(3H,

(M+), 208,

190,

181,

166,

139, 138,

120,

iii,

110, 97, 96, 83, 82, 81.

45,

9B. P. W i j i n b e r g

These

The o x i d a t i o n of 14 with Jones reagent.

acetone

M. C. Whiting,

(0.27 mmol)

at 0C.

A f t e r s t i r r i n g at ambient t e m p e r a t u r e
for 3 hr, the m i x t u r e was b a s i f i e d with
sodium h y d r o g e n carbonate
tracted with methylene
ml).

to pH'9 and ex-

chloride

(3 x 10

The combined extracts were washed

w i t h saturated aq sodium chloride,

and e v a p o r a t e d

dried

to give the residue w h i c h

was subjected to column c h r o m a t o g r a p h y

on silica gel
MeOH

(5 g).

E l u t i o n with CH2CI 2-

(9 : i) a f f o r d e d the diketone

(19 mg,

(~)

38.4 %), w h i c h was identical with

the authentic

sample o b t a i n e d above.

(1981).

Soc.,

and
1854

11E. N. Marvell and J. Tashiro,

Chem.,

~,

3991

13K. E. Pfitzner
Chem.

Soc., ~ ,

1433

(1980)

22, 5079

J. Chem.

(1954).

J. Org.

(1965).

T e t r a h e d r o n Letters,
in

(5 ml) was a d d e d freshly prepar-

ed Jones reagent

~,

and W. N. Speckamp,

12R. Green, F. Tonnard,

(50 mg, 0.24 mmol)

(1980).

S. Katayama,

iE. B. Bates, E. R. H. Jones,

data were c o n s i s t e n t with those of report1

ed one .

To a solution of 14

1373

and S. M. Weinreb,

3373

T e t r a h e d r o n Letters,

136,

and

Heterocycles,

Elution with CH2CI2-MeOH

(CH2CI 2)

(1979).

Y. Nakashita,

the residue w h i c h was subjected to column

(12 g).

4445

G. C. Gerrans,

b i n e d filtrate and w a s h i n g s were w a s h e d

1620; N M R

12, 563

and Sk. A. Ali,

6A. S. Howard,

1710,

and

J. Med. Chem.,

was r e m o v e d off by filtration.

: IR

Soc., ~ ,

(1969).

(20 ml) was added

(3 mg,

Roy.

(1952).

T e t r a h e d r o n Letters,

(~5)

J. Proc.

(1940).

S. Swann, Jr., and

into the above m i x t u r e and the p r e c i p i t a t e

dried,

J. Chem., ~ ,

Jr., J. Am. Chem.

~A. H. Beckett,

(30 ml) and basi-

fied w i t h sodium carbonate

Austral.

Soc. N. C. Wales,

2.81 mmol)

e v a p o r a t i o n of the solvent,

and

(1972).

and the r e s u l t i n q m i x t u r e was stirred at

for 15 hr.

S. R. Johns,

2F. Lion and A. M. Willis.n,

(40 mg, 0.35 mmol), was added d i c y c l o -

cm

microanalyses,

and m a n u s c r i p t preparation.

into 15 w i t h M o f f a t t

To a solution of ~

0.71 mmol)

and Miss

sample o b t a i n e d above.

The o x i d a t i o n of ~
reagent.

Miss H. Furuyama,

Y. N a r i t a of Hoshi C o l l e g e of P h a r m a c y

25.8 %), w h i c h was identical w i t h

the a u t h e n t i c

We thank Mrs. T. Ogata,

Miss M. Nagao, Mrs.

453

and R. Carrie,
(1973) .

and J. G. Moffatt,
5661,

5670

(1965).

J. Am.