The total syntheses of (+)-tetrahydroalantolactone and (±)-artemisin

Tetrahedron Letters No.23, PP, 2615-2619, 1966, PergamonPreen Ltd. Printed in Great Britain.

TOTAL smT~mss

THE

OF (+)-TMRIJIYDR~AUTOU~TOIOIS

AHD (a)-ARTEMISIB by Uaaao Nakazaki Department

of Ohemletry,

and Kolchlro

Faculty

Osaka Unlverelty.

19aemura

of Bnglneerlng

Toyonaka,

Osaka,

Science

Japan

(Received 29 )barch 1966)

(-)-Artemisln

(I)

the configurational

relationship

seaqulterpenesl)

, and its

a means to correlate terpenes

the catalytic

latlon

(IV)

the presence alcohol

(IIIa),

(IIIb),

we report

of

Following

with

of toluqulnone

(IV),

afforded

(Found:

C.71.54;

wae converted

b.p.134-135’/0.2 m.p.65-66’.

H, 7.77%)

into

The Robinson’s

anne-

metholodlde

the bicycllc

In

keto-

m~(logL4.19).

procedure 3)s

(VII),

by

mm, which wa6 then

m.p.58-59’.

sodium ethoxlde

(VI),

acetate

of

from the

mm, prepared

1-dlethylamlnopentan-3-one

Abe’s

dlenone

ayntheaee (II)

b.p.153-157’/26

(V), u1.p.l04~,h,x248

enol-acetate

the total

b.p.140-142’/30

to the ketone of

provides

of eudesmane aeequl-

(VII).

hydrogenation

the monoacetate

eudeamane

2) .

of gulananolidee

The -cle-glycol

oxidized

various

and (+)-tetrahydroalantolactone

same Intermediate

to establish

ready photoiaomerleatlon

communication,

(A)-artemleln

within

the configurations

with thata

In this

has been a key aubatanoe

(V) was converted

mm, which afforded A_,282

upon bromlnatlon

2615

into

mp(log5 followed

the

the

4.43) by

No.25

2616

(III)a Rdi b R=Ac

(IV)

(VI)

(V)

(VII)

ALANTOLACTONE (XIII)

(XIV)a R=C2H5 b R-H

-&t& &IQ (I) ARTEMISIN

(XVII)

2618

No.23

Into

4,

and co-workers

Clock8r

SinOe

(+)-tetrahydroalant~lactone

of this

compound

ne

(XIVb),

(II),

(XIVa)

n.p.197-199’,

and modlum acetate

122-123*,

the ready

was hydrolyzed

to give

epimerlratlon

lng with potamelum oarbonate Boiling

acid

then treated

infrared

h ,,286

the oily

epectrum

of an authentic

The authors

D. H. B. Barton,

Imperial

Pharmaceutical samples

mp(logt with

product

of artemlain.

was

3.28).

~elenlum (XVIII)

dloxlde which was

to afford

C,69.36;

B, 6.94s).

by the comparleon

and thin-layor

are indebted

Oollege,

the Reeearch

Indutatrleta,

(XVI),

of

lte

ohromatogram

(-)-artemioln.

&%nowledaement-

M. gwnl and T. Mlkl,

its

to the phenol

potaecllum carbonate

was established

abnorption

with thata

rearrangement

m.p.190-192°(Foundr

The identity

establiehed

the dienone

(XVI) wan oxidized

to yield

(I),

by reflux-

whore oonotltutlon

dlenone-phenol

with aqueous

(+)-artemlein

(IX)

m-p.

m.p.

r.p.267-268*(decomp).

The dienone

of which to

(XV),

(XV) to yield

* a max238 ap(logS4.06),

In acetic

with acetic

in

151-W.

(XVII),

to the hydroxy-

with dlchlorodlcyanobenzoqulnone

dehydrogenated

by It8

(XII)

synthesis

the lactone

in tetralln

dlouno

supported

the total

which was then treated

anhydride

oonSlguxmtlon.

to convert

thue accompllehed.

The hydroxy-ester sold

eucceeded

Osaka.,

London;

to Profemaor Dre. Y. Abe,

Laboratory,

Takeda

who generouely

provided

2619

No.23

1) W. Oocker and T. B. H. McMurrj, Tetrahedron,4, 181 (1960). T. G. Haeall and D. H. Theobald, Quart. Bev., &

101

(1962). 2) D. H. R. Barton, J. L. D. Lerl8allerand J. T. Pinhey, J. Ohem.

a00..

3472 (1962); D. H. B. Barton, J. T. Plnhoy

and B. J. Welle, u.,

2518 (1964).

3) Y. Abe, T. Harukaua, B. Iehlkan, T. HIM, H. Sum1 and T. Toga, J. Am. Chem. 800.; Et 2567(1953). 4) W. Oooker,

L. 0. Hopklne, T. B. H. McMurry and

Riobet, J. Ohem. Sot., 4721 (1961); W. Oooker Hisbet, &d,,534

(1963).

If.

A.

and H.A.