Dimethyl(methylthio)sulfonium Triflate as a Promoter for Creating

Pazur, J.H., in Pigman, W. and Horton, D. The Carbohydrates,. Chemistry and Biochemistry. Second Ed. 1970, IIA, 69. 9. Igarashi, K. Adv. Carbohydr. Ch...
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Chapter 7

Dimethyl(methylthio)sulfonium Triflate as a Promoter for Creating Glycosidic Linkages in Oligosaccharide Synthesis 1

Fredrik Andersson, Winnie Birberg, Peter Fügedi , Per J. Garegg , Mina Nashed , and Åke Pilotti 2

3

Department of Organic Chemistry, Arrhenius Laboratory, University of Stockholm, S-106 91 Stockholm, Sweden Dimethyl(methylthio)sulfonium triflate has been evaluated as a promoter in glycoside synthesis employing thioglycosides as glycosyl donors. Those having a participating group in the 2-position produce 1,2 trans-glycosides with high stereoselec­ tivity. A nonparticipatmg group in the 2 position usually gives a preponderance of 1,2-cis-glycosides. The addition of tetraalkylammonium bromide to the latter reaction mixtures (nonparticipating benzyl group in the 2-position) transforms the reaction into a halide-assisted one with enhanced selectivity for 1,2-cis-glycosidation. These novel methods makes it possible to construct oligosaccharides with the 1-position protected as a stable alkylthio (arylthio) glycoside. When required, the thioglycoside is activated with the foregoing thiophilic reagent, and the oligosaccharide is joined to the desired acceptor. Oligosaccharides, substances

as

either

lipids

biological

interaction

biological

information.

of is

some that

reaction intact. paper of

at The

will

devising the

Their

a

covalently are in

which

one

problems

address

the

hydroxyl is

that

second

synthesis

has

they

have

one

act is to

strategy

group(s)

of

while

stereospecific of

been

these

to

in

synthesis

protective-group

desired

linked

involved

efficient

Two main

second

oligosaccharide

or

proteins

processes

importance. of

free

or

two

extensively

a as

such host

other of

carriers

therefore be that

dealt

of a

allows

leaving

the

reviewed

The

One

chemical others

glycosylation. topics.

matter

with.

This subject

(1-12).

Current address: Institute of Biochemistry, L. Kossuth University, P.O. Box 55, H-Debrecen, Hungary Address correspondence to this author. Current address: Faculty of Science, Chemistry Department, Alexandria University, Alexandria, Egypt

2

3

0097-6156/89/0386-0117$06.00/0 ° 1989 American Chemical Society

118

TRENDS IN SYNTHETIC CARBOHYDRATE CHEMISTRY In

order

hydroxyl

mandatory. glycoside

On

at

the

opposite

side

classical

at

a

use

time,

of is

a

small

those

is

than

that

(J_3).

glucan

to

our

original

the

problem

glycosyl raise

of

having

by

in

were and

use

in

?,:ν· molar

),

yield CHC.i^).

bromides and

smaller

,Fi- T e i . r a

1

557.

This

the route

w

not

e

r

n

i

into

In

n

t

o

a

permit

us

to

of

the

phytochemical

clearly

not

to

suitable

the

use

of

recently

following

key

participating

(b.)

by

large

a

quantities

taken

the

benzyhdene

α

use

methyl blocks.

methods:

benzoyl

regio-

triflate The

m.p. in

the

with

methyl

184- 1 8 5 ° , presence

and

(c)

in

synthesis

is

disaccharide

preferable

to

one

of

(27)

bromide

(1

4,6 -0- b e n z y l i d e n e -

QaJ

2 , ΓαΊ 0 involving

U.6,



D

silver

(a)

groups

glycosylation

of (25i);

acetals

D-glucopyranosyl

condf>nsed

1,3--β-linked was

(J_3),

triflate-promoted

activated

0 benzoyl was

of

involving

dichloromethane of

the

megasperma.

(26).

O-giucopyranoside, m

of

defense

in

( 2 0 . 2 1 ).

carrying silver

illustrated

the

procedure

the

fragments;

cleavage

reactions

upon

in

the

was

therefore

laboratory

based

is

continued

glycosylation

this

was

the

equivalent)

1- t h i o - ( 3 t'MCI

in

Scheme

was

novel

the

are

to

Gram

synthesis

potential

encountered

This

did

in

and

they

tetrasaccharide 24"/..

for

original

Recourse a

a

above

required

thioglycosides

glycosylation outlined

step

our

reductive of

convert

this

donors

as

that

Phvtophthora

experimentation

2-position

making

selective the

that

glucosyl the

to

Extensive

synthesis

in

triggering

of

large

corresponds

heptasaccharide

Lonn

for

1

of

selectively

(14-20).

donors

this

developed

(24)

be

of

purpose.

of

may

the

performed

glycosyl

manipulations they

of

are

difficulties

-fact

synthesis

and

use

as

mould

thioglycosides

the

the

heptasaccharide for

most

reintroduced

in

monomer

disadvantage

severe

the

investigations,

The

use

to

by

yield

that

glycosyl

responsible

heptasaccharide

for

to

substi­

large

conversion

infections

halide.

the

having

one

of

that

One

the

been

although

branched

fragment

soybean

Those

adding

synthesis

for

he

protecting-group

become

to The

is

block

lead

advantage

activated

this

a

recently

synthesis,

1.

for

halides

yields

oligosaccharide

Scheme

approach

C-2

synthesis

fragments.

may

have

than

the

requires

this

Their

normal

large

glycosyl

diminished

to

rather

in

normally

into

donors.

stable

is

preponderantly

participating

in

reason

on

it

Thioglycosides glycosyl

C- 2

ring.

hahdes.

lead

or

at

C-2 to

pyranose

glycosyl

a

strategy,

main

condensations; in

or

usually

having

manipulations

oligosaccharides

result

are

amino

1.2 - t r a n s -

a

nucleophile

furanose

advantageous

The

rather

further

the

of

participating

incoming

donors

block

highly

protecting-group on

efficient

an

substituent

synthesis

substituent

and

oligosaccharides.

approach

the

the

glycosyl

carrying

1,2- t r _ a n s - g l y c o s i d e s .

give The

an

of

C-2

glycoside

nonparticipatmg

hand,

directs

CIS-glycosides,

tuent

a

requires

nonparticipating

1.2

1,2-cis;

a

C- ? .

other

that

the The

a

make

usually

substituent from

to

function

triflate f6°

(c —

initial

1.1,

to

7. ANDERSSON ET AL.

Glycosidic Linkages in Oligosaccharide Synthesis

119

Η

η »

M

ι

Ο

ι

ο

a

S

en

Ο

M

H

Ο

ts>

h*

7.

ANDERSSONETAL.

Glycosidic Linkages in Oligosaccharide Synthesis

121

122

TRENDS IN SYNTHETIC CARBOHYDRATE CHEMISTRY

protection glycosyl

by

position

2

m.p.

partial

acceptor. of

was

2

228-229°,

4

yield; [a J

1.2.3.4 L , a

and

+5°

1

-

converted

into

treatment

with

this

glycosyl

triflate

the

n

*~

*^'

The

also

The acceptor

of

group

activity

6 in

This to

a

give

e

3,

Π•• p o s i t i o n

m.p.

179

(28)

in

90"/.

glycosyl

then by

Condensation using

the

of

silver

m

5

837.

donor

for

181°,

and yield

acid.

compound

in

yield;

the

final

glycosyl

to

this

acceptor,

encountered,

namely,

derivatives of

expected

to

Attention

was

be

then

I.e.

more

of

it

reactions

with

turned

1.

had

and

phyto-

s y n t h e s i z e d (13.29).

the

utility

that,

the

quite

handling

leading

to

apart

of

methyl

may

be

2-hydroxy-

possibility

the

of

However.

disadvantages

of

glycosyl

unreactive

to

as

yield; l a

which

time

routine

in

the

" ^ hydrogenolysis

previously

other

and

with

by

found

the

group(s)

yield

oligosaccharides.

was

in

887.

937.

CHCI^).

with

triflate

demonstrates

synthesis

1.0,

in

5

in

retention

promoter,

severe

donor

material

byproducts,

therefore

7

methyl

heptasaccharide

involved

hydroxyl

give

using

promoter (c

treatment

deprotected

the

elimination

as

the

by to

(3- D - g l u c o ­ as

-18°

heptasaccharide

laboratory

glycosylation

"a"*

glycosyl

again

clearly

block

hazard

yield;

the

benzoyl

triflate

removed

the

synthesis

0

methyl

837.

spectra,

the

in

health

methylation

h

acetonitrile

of

was

identical

for

work

as

t

was

protected

n.m.r.

foregoing

thioglycosides

glycal

in

dichloromethane,

in

elicitor

triflate

product

quantitative acetic

key

s

in

condensation

the

the

dichloromethane

in the

1,2,3,4- t e t r a -

7

rotation,

other

a

final

debenzoylation

from

the

in

the

botane —

dichloromethane

using

6

dithiocarbonate

optical

in

in

precursor

with

5

promoter, gave the ο 20 ( ç 1.2, CHCI^).

The

near

the w

the

tetrasaccharide

hydrazine

in

5

dichloromethane

chloroacetyl

and

l

in

in

follows:

in

afforded

3^

was

Condensation p y r a nose

in

4

h

(25)

group

bromide

T

with

D g l u c o p y r anose,

yielded

C H ( : : l

ot

).

group

group

chloroacetylated

bromide

with

2-hydroxyl

).

was

hydrogen

It

as

),

α

CHCI

chloride

benzoy!~(3

CHCI

promoter

condensation. obtained

7

· ·

}

the

hydroxyl

Treatment

1.1.

hydroxyl

CHO

1.2.

bromide

as 6

[)

free

Tetra- 0

( c n

(c

aluminum a

(c

of

free

benzoylated. f15°

having

d

remaining

[a]

trimethylamine afforded

benzoylation

The

competing

acceptor,

glycosyl

more-specifically

donors. thiophilic

reagents. Regiospecific use

of

a

"soft"

fluoroboronate it

has

was

many

indeed

yields most was

in

reacts

in

in

in

(37)

a

sulfur

rapidly

with (32,33).

activating

were

by

was

glycosylation

alkyl

moderate.

glycosylation replaced

(DMTST)

of

center

should

require

Dimethyl(methylthio)sulfonium

applications

glycosylation

therefore

promoter

(.30)

acid.

synthetic effective

useful

triflate

activation Lewis

reactions triflate.

thereby reactions.

dimethyl In

sulfide

pilot

(3J_)

Triflates

and

experiments,

1 -thioglycosides,

(2_2 -24,,

the

tetra

have

3j4-3jB)

but

been and

the

it the

found anion

Dimethyl (methyl thio)sul fonium found

to

be

a

most

efficient

7.

The

result

usefulness

of

reactions 2

Glycosidic Linkages in Oligosaccharide Synthesis

ANDERSSONETAL.

and

acceptors

(1.2

a

is

the

shown

Yields Scheme

participating

an

gives

of

product.

The

this

two

to

human

colonic

and

to

condensed the

containing from

bromine

to

give with

moderate

yields

foregoing

product

27

In

26

the

of

benzyl

illustrates of

this

the

mixture.

for

studies

34

as

ones

for

by

trisaccharide fucolipid the

in

other

fragment accumulating

thioglycoside

(Scheme

3). a

the workers

In

25

this

complicated

of

the

1,2-elimination

was

treated

which

a-bromide, of

silver

was

with

was

triflate.

obtained.

an

in

was

then

Only

However,

acceptable

yield

under

of

the

using

was

(1

in

the

means

the

(28)

of

DMTST

in

was

a

non-

was

attempted.

promoter the

with

glycosyl

generated

pentasaccharide

phosphate-specific

an

having

the

group

simultaneous

29)

2-position

triester

experiment promoter

the

added

at

donor

compatibility

thioglycosyl in

involving (compound

axial

example,

to

and

room of

raises for

a

with Thus

mixture

the in

the

donors

2-position.

equivalent)

sieves

glycosyl

the

6

4),

groups,

in

provides

situ

a

receptors

in

model

and

the

(40).

general

group

by

a

mannose

a

(j43)

separated

existing

25

(Scheme

deprotected

equivalents)

molecular

of

quantities

gave

particular The

mannosylation

equivalents)

and

use

experiment,

DMTST

phosphoric

fibroblasts

benzyl)

(1.2

a

of

by

-glycosides

(41 )

The

efficient

illustrated

produced

27

group

presence

as

a

glycosyl

glycosylation than

a

26

presence

involving

synthesis

The

a in

product

hydroxyl

the

DMTST

an

syntheses

of

unit

triflate

example

two

The

of

the

group.

further

acceptor

the

the

CHC.I^)

D-giucosylated

This

adenocarcinoma, the

in

other

participating

uptake

is

synthesis

conditions,

a- m a n n o s y l a t i o n

In

method

corresponding

of

m

findings,

(39).

glycosylation

donor.

high.

unpublished

another

the

( £a ]^

of

acetyl

in

room

glycosides.

methyl

In

at

affords

DMTST

thioglycoside

previous

advantageous

considerable

25.

condensed

a

liver

of

an

the

equivalent)

2-position

position

repeating

with

(1

sieves

with

in

glycosyl

the

compounds

does

more

of

In

the

the

experiments,

of

2 amino-2-deoxy-(3

the

the

use

product

the

of

pure

2

groups

these

acceptor

uniformly

1.2-trans

laboratory.

mixture

the

examples

In

mixture

molecular

than

in

hydroxyl

hexopyranoside

a

in

testing

1.2- t r a n s - g t y c o s y l a t i o n

accordance

group

potentially

corresponding

be

In

are

usefulness

instance,



protected

of

experiments

in

(.38).

glycosyl

yields

yields

is

following m

a

2 to

isolated,

2.

group

synthesis The

of

higher

synthesis

the

the

benzoyl

N-phthaloyl

procedure

Scheme added

and

model

suitable

containing

temperature. in

of

in

are

of

promoter

glycosylation of

was

equivalents)

dichloromethane

donor

a

6-positions

equivalents)

given

number as

involving

,3-,4

(4 — 5

of

DMTST

glycosyl

of

the

question

synthesis a

column

the

nonparticipating DMTST

the

thioglycoside

acceptors

Yields

chromatography

10

(4 — 5

(42),

containing of

isolated on

silica

use

1,2-cis-

the

dichloromethane

temperature.

of

of

(such

molar donor 16

31

(20).

4Â product, gel,

are

123

g

ο

!

ο

i

ο

2

w ο

m

h*

ι

r

δ-

î Ι

Γ-

I

r

>

Ο

GO

1

§

ο

ι

i