A new route to branched-chain sugars by C -alkylation of methyl glycopyranosiduloses

Tetrahedron Letters No.28, pp. .32j9-3242, lY6H.

Pergamon Prws.

I'rllltvdin Grrat. Britain.

A NEW ROUTE TO BRANCHED-CHAIN SUGARS BY C-AIKYLATION OF METHYL GLYCOPYRANOSIDULOSES R.F. Butteworth,

W.G. Overend and N.R. Williams

Department of Chemistry, Birkbeck College (University of London), Malet Street, London, W.C.l

(Received in UK 3 April 1360; azsc~:tej.fnr +h!icirIw.

2: Ail,;: :,j&l

The isolation and chemical study of new antibiotic substances during recent years has resulted in the discovery of several interesting branched-chain sugars and has led to an examination of methods for the chemical synthesis of sugars of this Several procedures have been reported (l-5) which utilise derivatives of

type.

either methyl glycosiduloses or glycosuloses as intermediates. the C-alkylation

We report now on

of methyl glycopyranosiduloses using either barium oxide and

methyl iodide or the enamine alkylation method of Stork ef &.

(6) to give

branched-chain sugar derivatives. For example, methyl 4,6-~-benzylidene-3-deoxy-cr-D-erythro-hexopyranosidulose = (I) , m.p. 113-114°, [a],+

105' (5 1, chloroform)

, prepared in 80% yield by

oxidation of methyl 4,6-O-benzylidene-3-deo~-~-~-arabino-hexopyranoside

with

ruthenium tetroxide (7), when treated in rj,fi-dimethylformamidewith excess of methyl iodide in the presence of barium oxide afforded methyl 4,6-s-benzylidene3-deoxy-3-C-methyl-a-g-hexopyranosidulose [a],f

48" (s 1, chloroform), vmax

(III)* (65%) as a colourless syrup,

1750 cm.-1 (C-=0). When sodium hydride was

used instead of barium oxide the same C-methyl product (III) was formed together with some decomposition products, as shown by thin layer chromatography. When the glycopyranosidulose

(I) was heated under reflux with a slight

excess of pyrrolidine in benzene with passage of the condensate through a

3239

3240

No.28

molecular

sieve

pyrrolidine cc

enamine

compound (II)

were

with

(III)

methyl

compound

18 was were

the

the

the

;5.5-6.3

(3

protons)

methyl

were

protons

anomeric

and

the

proton

to

to

the

substituent

III

(II),

singlet

at

x

the

with

group of

C-3

in

the

was

prepared

in

compound

compound

III

prepared

samples

of

contaminant

of

their

product in which

dimethylformamide it

the

s per tral

was

n.m.r.

from

group

evidence)

to

C-3

III by

at

from

protons

atZ

assigned

to

group;

c8.62

the

the

the

singlet

H-3

of 2.55

benzylic

and

four

gave

(3 protons)

was

protons

rise

was

indicated

by

at

r6.55

to

a

assigned

the

is

C-3

the

three

methyl

a trace

to

located

in

triethylamine the

isomeric

an equatorial

identity was

results

a small

that

could

be Assumj ng

implies

methods

amount

that of

was

supported

position

(i.r.

by

indicated of

stored

compound

the

the

that

(IV)

the

an isomeric

When compound

was equatorial.] of

into

this

spectral

fact

82% yield.

The

different

contained

group

in

axial.

[These

methylations

III

oxidation,

disposed

the

(8)

compound

during

quantitatively at

compound

five

and H-6($;

III

afford

spectra.

containing

epimerised

methyl

the

the

compound

count

at 7: 5.45

methoxyl

compound

occurred

C-3

similarity

of

proton

the

4.45

H-6@),

doublet

tetroxide

had not

at

this

C-3. at

ruthenium

of

C-methylated

a sample

as a singlet

of

Treatment

an unambiguous

follows:

protons

42’

oxide.

as

The

at

with

[xl,+

characteristics

gave

assigned

H-5,

138-139”,

spectral structure

compound

H-4,

at y7.0.

m.p.

hydrolysis

appeared

assigned

epimerisation

samples

had

these

of

a crystalline

4,6-O-benzylidene-3-deoxy-3-C-methyl-a-D-altropyranoside =

methyl

week

and

assigned

and barium

spectrum’

reaction,

90% yield,

n.m.r.,i.r.)

iodide

stereochemistry

oxidised

wet

the

(t.l.c.,

the

and n.m.r.

and subsequent

centred

The

infrared

in

in

iodide

was due

methyl

formed

with

were

multiplet

produced

accord

n.m.r.

phenyl

at

was

methyl

obtained

proton;

the

(II)

identical

I with

From

water

The

in

(70%),

t;:at

remove

chloroform).

1,

the

to

for

III

one

which and n.m.r.

in

3841

No.28

The methods deacribcdhave been used to C-methylateother

rtl@

glyco-

pyranosidulosederivatives&.A. methyl 4,6-g-bensylidene-2-deoxy-a-D-orvthrohexopyranosid-3-ulose which alkylatesat C-2; and methyl 3,4-z-isopropylidene-ag-ervthro-pentopyranosiduloae which is methylatedat C-3). The results of thee. and related syntheseswill be reportedlater. The new branched-chainsugar derivativesof types III and IV are of considerableinterestbecause,by virtue of reactionsat the carbonylgroup of the kind alreadyreported from our Laboratory,they can be induced to un&rgo furtherreactionsto give modified cougars containingbranchingat two sites and to afford branched-chainamino-sugars. Preparationsof modified sugars of theme types are being examined. RSPRRRNCRS 1. J.S. Burton,U.G. Overend and N.R. Williams,2. w. 2. W.G. Overend and N.R. Williams,2. w.

*.,

&.,

3433 (1965).

3446 (1965).

3. A.A.J. Feast, W.G. Overend and N.R. Williams,2. -Chem. Sot. C, 303 (1966). 4. B. Flaherty,W.G. Overend and N.R. Williams,J. -Chem. Sot. C, 398 (1966). 5. A. Rosenthaland L. (Benzing)Nguyen,TetrahedronLetters,2393 (1967). 6. G. Stork, R. TarrellandJ. Ssmuszkovicz, -J. Am. -.-VChem. Sot., 76, 2029 (1954). Chem. Sot. C, 7. P.J. Beynon, P.M. Collins,P.T. Dogangesand W.G. Overend,2. -1131 (1966);P.J. Beynon.P.M. Collins,D. Gudiner and W.G. Overend, Carbohvdrate&., in the press. a. A.A.J. Feast, W.G. Overend and N.R. Williams,2. a.

s.,

7378 (1965).

3242

No.28

*Satisfactory elemental analyses were obtained for all new compounds. 1 N.m.r. spectra were measured on solutions in CDc13 with Me4Si as internal standard with a Varian A-60 (60 MHa) instrument.

0-CH

2

I PhCH-0

u4e

0

0 I

OMe Me

0 III