Synthesis of L-daunosamine from D-glucurono-6,3-lactone

oo40-4039/87 $3.00 + .OO Pergamon Journals Ltd.

Tetrahedron Letters,Vol.28,No.l2,pp 1327-1328,1987 Printed in Great Britain

FROM

SYNTHESIS OF L-DAUNOSAMINE M.K.Gurjar* Regional Summary:lactone

Research

into C-l/6

owing

to

clinically

sugar that

several

moiety

of

daunosamine, curtailed.

g-Glucurono-6,3-

lactone

are

anticancer

then

the we

carbon

transformed

immense The

of D-Glucose crucial

step

report

of

a new

aminosugar

common

C-l/6

it

was

transformed

epimerisation

approach

at

for

feature

of the starting

However, are

interest

has been synthe-

’ . The atoms

of daunosamine.

C-1/6

of

activity.

precursors

is that

C-1/6

subject’

all the antyyyclines

carbohydrate

Herein

from

the

the

useful

in almost

atoms

be

are

syntheses

remain

if carbon

of

by a new approach.

present

in all the

007, India.

synthesised

C-6/1

antibiotics

their

from

observed

been

atoms

of aminosugar

&-daunosamine) sised

has

carbon

Anthracycline

and S.M.Pawar

Laboratory,Hyderabad-500

&Daunosamine in which

D-GLUCURONO-6,3-LACTONE

the

realised

into

C-6/1

C-5

could

synthesis

of

L-daunosamine. Commercially from

available

D-glucose)

Introduction

of

was the

chloride-pyridine tri-n-butyltin the

5-deoxy

with

dry

methanol

protected

2

and

(2)’

-glycosides

as benzyl

ether

0,

Compound

6 and ethanethiol

at

afforded

converted

and IR 120 resin.

chloride

into

methyl

2 was stirred

to afford

the 6-deoxy

sulphonyl

chloride-pyridine

placement 100” then ted

into

effected5

the

87% yield. hydroxyl

derivative the

with

hemiacetal (2

excess

group

toluene gave

of which

was

of cont.

and silver

hydrochloric

1 which with 5 (60%).

by refluxing

of ft

reflux

bromide

of Raney

with

Treatment under

with benzyl

in the presence

gave

sulfuryl

of AIBN in refluxing

free

glycoside

with

(z14.

dechlorination

120 (H) resin

the diethylmerchaptan

-78“ in methylene

4 was

amount IR

was

(obtained

derivative

reductive

by the reaction

to give 6 (54%).

then

C-5 on

in overall

oxide in benzene

acid

at

Amberlite

(4

1,2-isopropylidene

which

and catalytic product

of o(,P

as

atom

afford

hydride

gave

a mixture

chlorine

to

e-Glucurono-6,3-lactone

protected

with

nickel

DIBAL

Compound methanol for 2 days

-10 (65%) which was treated with methaneto give the 3-mesylate dis-11. Nucleophilic reaction of -I1 with sodium azide in dimethylformamide at yielded the azido-derivative -12. Compound -12 has been conver-

&-daunosamine

product

hydrochloride

(13) -

and hydrolysis?

1327

in two

steps

-Via reduction

1328

OR g

R=H

2

R=Me

2

1

R=H

5 R=Bn

-12

10 R=H 11 R=Ms

It is pertinent suitable

to

in natural

to

prepare

products

The authors

mention

that

the

2,6-dideoxy-L-sugars and are prepared

procedure which

by lengthy

thank Dr.A.V.Rama

are

reported of ten

above

is

encountered

routes.

Rao for his keen interest.

REFERENCES

5. 6.

W.A.Remers, The Chemistry of Antitumor Antibiotics, Wiley Int., New Jeresy, 1979, Vol. 1, ch. 2. F.M.Hauser and S.R.Ellenberger, Chem. Rev., 86, 35 (1986). M.K.Gurjar, V.J.Patil and S.M.Pawar, J.Scixnd. Res., in press. R.L.Whistler and J.M.BeMiller, Methods in Carbohydrate Chemistry, 3, 177 (1980). H.Parolis, Carbohydrate Res., l&, 21 (1983). T.Irimajiri, A.Yoshida, T.Ogata and S.Incokawa, Bull. Chem. Sot.

7.

G.Medgyes

1.

2. 3. 4.

Japan, 43, 3242 (1970).

(Received

in

and

J.Kauzmann,

UK 5 January

1987)

Carbohydrate

Res.,

x,

225 (1981).