Methods for Introducing Atoms Other than Oxygen into Sugar Rings

8 Methods for Introducing Atoms Other than Oxygen

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into Sugar Rings ROY L. WHISTLER and ABUL K. M. ANISUZZAMAN Department of Biochemistry, Purdue University, Lafayette, Ind. 47907

Introduction In the last fifteen years some attention has been directed toward the production of modified sugars wherein the normal ring oxygen atom is replaced by another heteroatom. In some instances syntheses have been induced with the desire to create analogs which might possess interesting and even potentially use ful properties and in some instances synthesis has reflected simply a basic interest in chemical structures and reaction chemistry. Our laboratory originally became interested in sugar analogs with sulfur replacing the ring oxygen because we antici pated that such analogs, but especially the analog of D-glucose, might possess new and useful biochemical effects. Our first sulfur analog was methyl 5-thio-α-D-xylopyranoside where the sulfur was locked into the ring by glycoside formation (1). Although we thought we were the first to introduce sulfur into a sugar ring and so commented at the time of writing, two other groups (2,3) reported 5-thio-D-xylose with the suggestion of sulfur as the ring heteroatom in November 1961 while our methyl D-xyloside analog manuscript was received by the Journal of the American Chemical Society on December 2, 1961. Since that ini tial period many sugars with ring atoms of sulfur and some with nitrogen, selenium and phosphorus have been prepared. Those with the greatest biochemical interest and hence with the greatest potential medical value have, so far, continued to be the sulfur analogs. This review will report a short description of methods for introducing heteroatoms that may become part of the sugar ring system. Introduction of potential ring heteroatoms may be accom plished rather easily, in general, by simple nucleophilic dis placement of a good leaving group such as the p-tolylsulfonyloxy or methylsulfonyloxy. This technique works well for primary po sitions and usually well at chiral secondary positions where the 133

In Synthetic Methods for Carbohydrates; El Khadem, H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.

134

SYNTHETIC METHODS FOR CARBOHYDRATES

enantiomorphic Naturally, applied

o r

capable a

obtained other

o f

placed

carbon of

or

form

giving r i n g a i n

o r

o f

a

e q u i l i b r i u m w i l l

p o s i t i o n

t o

higher give

t o

involving c i t y

o f

e x i s t

a

higher

r i n g

substituents

a

n e g l i g i b l e

while

i n 4-thio-g-glucose Normal oxygen a

family

a c y c l i c

form

i n c l i n e d

o f

predominating a c e t y l a t i n g

isomers a

Of

by

glucose.

o f

sugar

analogs

monosaccharide

i n enzyme

5-thio-D-glucose that

i s

analog

not a i s

for

large

ber

o f

highly

2

>

s t a b i

are

i n

have

This

w i l l r i n g

n u c l e o p h i l i -

-NH > -0H> 2

are

the a

give

s o l u

present

prevalent

p r o c l e v i t y amount

also

t o

o f

appears

β-D-fructofuranose a c i d

c a t a l y s t

i s

t h e a c y l i c

a

heteroatom

biochemically

(UDPTG)

as

u r i d i n e

have

shown

reactions.

acts

agent

c o n t r o l l i n g

nor a

t o x i c

substance

continuously

a

Since

r e v e r s i b l e

examined

i t s present

new s i m p l i f i e d A unique

increases

a

Most

f i r s t

hormone

as

with

under

5 - t h i o -

the a c t i v i t y

o f o f

other pathway

5 ( 5 - t h i o - a unusually

c o n t r o l male

(6).

UDPTG

use

o f

male

f e r t i l i t y This

sugar

a n t i c i p a t e d

o f

than

5 - t h i o - D -

s i g n i f i c a n t l y

synthesis

synthesis

feature

i s

i t s g l y c o l y t i c

such

alone

desirable. i t

(5)

Lewis

analog,

analogs

c o n t r o l l e d

amounts.

percent

to

isomers

w i l l

o f

f a i r

i s t h e

being

steps,

amounts, 500

I t

a

with

containing

i n t e r e s t i n g

D-glucopyranosyl)pyrophosphate

f e r t i l i t y .

i s

shown

with

o f

close

membered

t h e sugar

forms

furanoid

t h e main product

and i t s nucleotide

fulness

furanose

isomers

and

i n 5-thio-D-glucose

always

i n t h e presence

f a r t h e most This

analogs

t h e have

H

the

pentaacetate.

a l l the

oxygen,

o f

occur.

p

to

carbon

r e l a t i v e

with

-SH>-

5-Thio-D-fructose

conditions

keto-D-fructose

that

i n s o l u t i o n

mixture

but

-SeH>

(4)

ketosesT

present.

toward

i s

carbon

the rings

w i l l

and

normal

than oxygen

The order

show

i n

may r e a c t

t h e i r

isomers

o r

size

and s i x

be

produce

The various

group

o f

to

pyranose

may o p e n

t o

ring

aldose

carbonyl

hydroxyl

opening

p o r t i o n

been

i t w i l l

While

five

n u c l e o p h i l i c

carbonyl

that

epsilon

ring.

i n proportion

an

on the

the

the r i n g

proper

more

have

carbon

stable

o r

t h e p a r t i c u l a r nucleophile.

only

so

depend

attack

membered

population

tions

form

sugar

carbony1

a c y c l i c ando f

t h e

C-5 o f

the heteroatom.

hemiketal,

Experimental r e s u l t s

form.

ketose

moderately

a

carbon.

the monosaccharide

carbon

on the d e l t a

seven

with

reactive

NHCOR.

o f

o f

heteroatoms

react

o f

o r

on the

i n a

s t a b i l i t y and less

r i s e

part

a

o f

procedures

discussed.

s t a b i l i t y w i l l

and, on occasion,

When

a

attack

portions

p o r t i o n

l i t i e s .

be

C-4,

C-6 of

t h e oxygen

hemiacetal

forms

i n v e r s i o n

can n u c l e o p h i l i c a l l y

various

minute

become

c h a r a c t e r i s t i c s

group a

w i l l

hemiketal

by

introductory

carbon

The r i n g

monosaccharides carbonyl

to on

C-5 o r

ring.

e l e c t r o n i c

to

these


hemiacetal

furanose


i s o f

heteroatom

normally

sugar

form

number

a n d some

The is

a

demand

involves

a

num

5-thio-D-glucose i s

glycogen

that,

i s

i n

s m a l l

synthetase

some

(7).


8.

Sugar

Rings 1.

Containing

N u c l e o p h i l i c

Nucleophilic most

widely

with

a t h i o a k y l

as

used

charide the

xide,

thiocyanate

reduced group

(1)

with

sodium

y i e l d s

a n d require

primary, of

a

good

a p r o t i c

with

allowed following

Best

s u l f u r .

Among

groups

d e r i v a t i v e s t o remove

t h e benzyl and t h i o -

i n ammonia

a n d t h i o s u l f a t e times

i n

been

d i f f i c u l t

conditions

require

been

displaced

i n t h e synthesis

5-thio-D-ribopyranose (11), 5-thio-D-glucose 4-thio-D-xylose

(JL6) s t r u c t u r e s .

parative

sequences

a n d i s easy

were t o

used

(9,10), (12),

6.

t h e f o l l o w i n g

a t

(DMF).

thiobenzyl, o f

5 - t h i o -

6-deoxy-44 - t h i o - ^ -

(15), a n d 6 - t h i o - D -

The method

5-thio-g-fructofuranose,

r e a c t i o n

with

A l l

than

t h e use

as N,N-dimethylformamide

(13,14),

most

a t primary carbons.

a r e more

o r

poor

displacements

have

such

anions

(8)

give

have

(1-3),

require

a r e u s u a l l y

Thiocyanate

l i t h i u m

by

a r e b e n z y l t h i o -

nucleophiles

positions

such

monosac-

carbon,

b u t these

reduction

these

oxygen

t h e sugar

used

ammonia

o r i s

t h i o l a c y l

groups

D-ribofuranose t o prepare

anions

ester

a

containing agents

i n displacements

o r t h i o l b e n z o y l

galactoseptanose

form

(tosyloxy)

nucleophile

solvent

thio-D-glucofuranose

(15 )

long

Hence

a t secondary

p-Tolylsulfonyloxy

and

deblock

Thiocyanate

rather

Groups.

blocked

t h e carbonyl

i n l i q u i d

(2).

a p p l i e d

D-xylopyranose

w i l l

Thiobenzyl

a s may be expected.

t h i o l a c e t y l

Commonly

i n a properly

by reduction

carbons.

displacements

s u l f u r

and 1,2-diphenylethane.

borohydride

s a t i s f a c t o r i l y

by a

d i s p l a c i n g

t h e t h i o l .

a r e cleaved

secondary

ring

Sulfonyloxy

monosaccharide

o r t h i o s u l f a t e

form

sodium on

a

t o attack

containing

as toluene

s u l f a t e

group

acetolysis

t h e stable

s u l f u r t o

o f

p - t o l y l s u l f o n y l o x y

because,

s u l f u r

other

reduction

a

f o r r e p l a c i n g

d e r i v a t i v e , o f

o f

(mesyloxy)

i s used

introduced

a c e t y l a t i o n

Displacement

o r t h i o l a c y l group.

t h i o l a c e t y l

135

into Sugar Rings

Sulfur

displacement

methylsulfonyloxy


Heteroatoms

WHISTLER A N D A N i s u z z A M A N

was recently

While

s e v e r a l

i l l u s t r a t e s t h e

conduct.


used

p r e -

136


Here (40%) at

1,2-£-isopropylidene-|j-sorbopyranose,

with

0°

to

an

equimolar

produce

the

y i e l d s

the

a c e t y l

d e r i v a t i v e ,

t o s y l

di-O-acetate, 4

fluoroacetic

a c i d

fructopyranose,

at

80°. on

methoxidej" produces

t i v e l y

methyl

t i v e l y

tosylated

indicated

i s

w i t h

2,

which on

3~~is

high

above,

but

chloride


converted

potassium

Hydrolysis of

4

to

the

t h i o -

t h i o l a c e t a t e w i t h

i n

aqueous

deacetylation,

i n

methanol

5-thio-D-fructofuranose,

1,3-0-benzylidene-L-sorbofuranoside i n

tosylated

t r i -

3,4-di-0-acetyl-5-S-acetyl-5-thio-P-D-

which

sodium

as

1,

p-toluenesuïïonyl

Compound

r e a c t i o n

y i e l d s

5,

of


3.

by

N , N - d i m e t h y I f o r mamicfe


q u a n t i t y

y i e l d the

at

C-5

number

of

and

the

containing

6.

A l t e r n a -

may

be

selec-

reactions

synthetic

steps

continued i s

increased. 5-Thio-P-D-fructofuranose, α-D-is

also

produces sugar

obtained.

the

thiophene

d e r i v a t i v e s

r a t i o n

to

mineral

by

a c i d

very

where

a

somewhat

excellent

compound

d e r i v a t i v e

that

be

subsequent

ribofuranose degradation i n

a c i d

anhydride

i s

easy

from

more

thiophene,

also

convert than

i n

to

the

mono-

and

r e a d i l y

degradation

of

that

desatu-

s i m i l a r

compounds

degree

the

i n d i c a t i o n

than

s t a b i l i z e d 5 - t h i o - D -

4-thioaldoses the

5-thioketose

room or

groups

to

the

converted

to

of

I t the

nucleophile

forms

the

at by

i n

can

glycosides

displacement

the

preparation

and

be

but

r e a d i l y

d i r e c t l y being

sugar or

Displacement

groups

cold

methyl

2,3-di-O-isopropylidene

0-4.

the

acetate

acetochloro

i s

t h i o l a c e t a t e

blocking

temperatures

base.

p-tolysulfonyloxy s t a r t i n g m a t e r i a l i s

t o s y l a t e d

stable

i n p y r i d i n e ;

converted

further

at

i s

The

e a s i l y

hydrolysis

which

of

s u l f u r

(20).

which can

a

4-0-p-toluenesulfonyloxy

be

acids

example

containing

j-lyxopyranoside

phene

r e a c t i o n

obtaining

less

is

but

temperatures

undergo

decompose the

anomer high

(19).

4-thio-D-ribofuranose

and

form

furan

makes

Mineral

to

or

There

The

of

major

acids

7.

ketoses

energy,

easy. but

Another by

formation

(17)

the

thiofuranose

The~~possibility of

thiophene

r e a c t i o n

i s

strong


the

induced

(18).

6

of

d e r i v a t i v e s .

higher"resonance

fructose to

of

thiophene

polysaccharides aldoses

Use

gives

the

the

slow

dehydrates

acetylated

s u l f u r

4 - t h i o - D -

undergoes

stable.

using

of

introduces

to

by

t h i o a c e t i c i t

can

normal reactions

and

nucleosides

Further (13,21,22).


8.

WHISTLER

Heteroatoms

AND A N i s u z z A M A N

137

into Sugar Rings


OAc

• CH OAc 2

Although

displacement

ion

normally

ous

rearrangement

t i o n

o f

proceeds

methyl

t h e sulfonyloxy

i n v e r s i o n

and i n v e r s i o n

2,3-

rhamnopyranoside, expected

o f

with

o f

group

by t h e

configuration,

c a n also

occur.

Thus,

simultane t h e

reac

0-isοpropy1idene-4-0-p-1οlyIsu1fοny1-a-L-

8 with

potassium

6-deoxy-4^thio-Ir-talose

thiolbenzoate


gives

n o t t h e

9 b u t methyl 5 - S -

benzoyl-6-deoxy-2,3-0-isôprypylidene-5-thio-O^L-talofuranoside, 10 y s i s

(2'3).

Reaction

talopyranose, size

o f

10 w i t h

a n d deacetylation^gives 11.

contraction

I n general under

a

sodium

methoxide

c r y s t a l l i n e L-rhamnose

number

o f

followed

by

a c e t o l -

6-deoxy-5-thio-£tends

conditions

t o

undergo

(24,25).

CH„ H-OSBZ OMe

C(CH3)

2

10


ring

138


Reaction

of

Qxirane

Terminal hexoses,

and

r e a c t i o n

with

for

s u l f u r

s i s

of

oxirane are

r i n g s

are

convertable

thiourea.

i n t r o d u c t i o n

e a s i l y

i n

good

produced,

y i e l d

A

good

example

of

that

used

one

5-thio-D-glucose

(26).

i n

Here

produce

t o s y l a t e d

C-6

saponifies

a l l o w i n g

the the

0-6

t i o n

of

urea

produces

Acetoxy

the

to

produces

and

the

then

benzoyl

oxygen

t e r m i n a l

attack

conditions s i s

ester

to

group

epoxide,

expected

12.

t h i r a n e

p r e f e r e n t i a l at 13

which

with

C-6

form.

~

at

the

the

i n

r i n g s

of

t h i s

f o r

the

i n

the

cold

form

the

C-5

primary

t o s y l

This

on

r i n g

w i t h

i n

14,

use

route

to

gives

sodium

5Êhio-D-glucose,

the

benzoylated

displace

e s p e c i a l l y

t h i r a n e

by method

synthe-

3 - 0 - b e n z y l - l , 2 - 0 -

i s

the

to

i s

isopropylidene-D-glucofuranose A l k a l i


Rings

w i t h

forma-

w i t h

i n v e r s i o n of

r i s e

e a s i l y

p o s i t i o n

group

treatment

l i q u i d

to ester.

under

t h i o C-5.

a c e t y l a t i n g

ammonia

and

h y d r o l y -

c r y s t a l l i z e d i n

the

a-D

~~ ÇH OA ζ c 0

C ( C H

The p r i a t e

oxirane

potassium


t o l y l s u l f o n a t e methoxide the

s t r u c t u r e

can

be

obtained

5 , 6 - d i - 0 - p - t o l y l s u l f o n y l d e r i v a t i v e d e r i v a t i v e

forms

t h i r a n e

r i n g

CH OTs 0

ι ^

H-CO-TS

to

a

produce that

on

5 , 6 - e p i s u l f i d e can

proceed

i n

CH SAc 2

H-COTS

the

the

by

from

the

)

2

an

appro

a c t i o n

of

6 - S - a c e t y l - 6 - t h i o - 5 - 0 - p -

treatment r i n g

also

3

(27).

normal

w i t h

cold

Further

sodium opening

ways. CH„

CH


of

8.

Heteroatoms

WHISTLER AND A N i s u z z A M A N

into Sugar

Rings

139

Another way of forming thirane rings from terminal oxirane rings i s by treatment with thiocyanate anion (28). H2

Î> âss>

H-C'

HÇ-S

H C-S-CN

1

N

© CN

H-C-0

v

H-C-O


CH„ H-C-O-CN

7

N

+

CH

®OCN

I S t i l l another route to an appropriate terminal thirane ring is from the 5,6-dideoxy-5,6-dichloro sugar derivative produced, for example, from 3-0-benzoyl-l,2-0-isopropylidene-a-Dglucofuranose by reaction with a mixture of carbon tetrachloride and triphenylphosphine (29). Thiolacetate easily displaces the primary chlorine anion and subsequent treatment with potassium hydroxide causes the S-6 sulfur to displace the secondary chlorine to form the expected thirane ring with normal inversion at carbon C-5. CH_OH H.CC1 2ι H

C

S

A

c

A possible mechanism for the halogenation reaction is shown. Ph P:

CCI.

3

Ph PO 3

Ph PClCCl 3

RC1

ROE 3

®

Θ

Ph FORCI 3

CHC1„

Direct opening of an oxirane ring by a nucleophilic sulfur compound may also be easily effected. Thus 5,6-anhydro-l,2-0isopropylidene-a-D-glucofuranose on treatment with sodium Cfrtoluene thioxide produces the 6-S-benzyl-6-thio compound (16). Treatment of 1,6:3,4-dianhydro-P-D-galactopyranose, 15 (4) with a-toluenethioxide produces preferential attack at C-4 with forma tion of the D-glucose derivative, 16. The 1,6-anhydro ring i s not


140

S Y N T H E T I C M E T H O D S FOR

opened

under

Reductive a c e t o l y s i s the

the

gives

of

the

forms

glucopyranose to

pyranose

of

the

i n

analog

s o l u t i o n ,

forms,

of

group

i t s

r i n g

is

i n

great

followed or

hydrolysis

acetate.

or

Since

e q u i l i b r i u m w i t h

produces

i n d i c a t i n g the

s t a b i l i t y .

by

i t s

p r i n c i p a l l y the


acetates

s u l f u r

because

benzyl

4-thio-D-glucofuranose

underivatized sugar

isomeric


conditions

removal

CARBOHYDRATES

other

4-thio-D-

a

7:3

comparative

r a t i o

of

furanose

greater

s t a b i l i t y

forms.

C I ^ C I ^ S

Oxetane

Ring

Oxetane the

same

r i n g

way

Opening rings as

can

are

be

use

i n

carbohydrates

nitrogen

i s

with

D-xylopyranose l a t t e r

the

and

compound

by


rings.

for

The

only

rings

i n

from

with

Treatment

i n

group

allows

C-5

by

the

i n s e r t

occurs

on

the

0-3

displacement to

group. a c e t y l

oxygen

of

the

s u l f u r

major

C-5

treatment

displacement

and

produce

the

p-tolysulfonyloxy

at

dimethylformamide

to

and

with

at of

s i m i l a r

displacement

5-azido

d e r i v a t i v e

and

also

of

1,2-0-isopropylidene-a-

or

sodium

a

The

to

the

oxetane

oxetane group. the

s t e r i c oxygen

the

6-0sodium

n u c l e o p h i l i c r i n g

by

azido

the

i n

group

at to

on

ensuing

of

the

ring

configuration

hinderance occurs

metho-

attack

Opening D-gluco

QKtoluenethioxide

Due with

without

methanol w i t h

r e e s t a b l i s h

150°, occurs

much

oxetane

3-0-acetyl-l,2-0-isopropylidene-5-0~

triphenylmethyl removes

s u l f u r

i n

of

1,2-0-isopropylidene-P-^-idofuranose.

made

p-tolylsulfonyl-a-D-glucofuranose xide

reagents

example

i n t r o d u c t i o n of

3,5-anhydro

i n

i s

opened

oxirane

N, N at

C-5

C-3 (30).

give

(31).


the

the A

8.

A l t e r a t i o n I t s u l f u r

of

i s at

E x i s t i n g

sometimes an

p a r t i c i p a t e

Sulfur

i n

the

is

often

be

isomerized

sought or

to

caused

ing

reactions

to

produce

the

preparation of In

the

i n s e r t

sugar

the

to

find

good

i n

monosaccharide

a

ring.

s u l f u r

undergo

the

methods

i n t o

a

structure

sugar

methyl

intermediate

serve

desired.

s t a r t i n g material.

excise

carbon

i n the

and

the

isopropylidene

benzyl

ammonium t o by

a

The

groups

produce

Methyl y i e l d

one.

Thus,

of

group

and is

r e d u c t i v e l y

long

free

displaced

r i z e d

Raney

n i c k e l

by

D-glucofuranose.

by

to

This

cold

to

i s

then

This

opened This

introduce

w i t h

a l k a l i benzyl

product

t h i o l a c e t a t e This

i s

product

the

sugar.

the

a c e t y l

remains

i s

group

the

to

to

a may to

o x i d i z e d to

a

sodium

i s

to

glycoside

i n

l i q u i d

prepared

i n

good

1 , 2 : 5 , 6 - d i - 0 -

i s

t o s y l a t e d

and

the

the

a t

0-3,

sugar

the

d e s u l f u -

group

produce the

w i t h

and

the

the

i s i s

not

Under a c i d i c

benzoylated

group

to

displaced by

excise

oxidized

by

to

conditions

with

carbon

one

oxide

but

methanol

the

methyl

5-0-benzyl-2-deoxy-4-thio-D-erythropentofuranoside

i s

formed

and

i n

l i q u i d

ammonia.

One

the

of

containing

the

treated

with

d e r i v a t i v e

with

However,

most

s u l f u r ,

fructopyranose i s

benzyl

while

major and

loss

from

s u l f u r

i s

is

not

i n

i s

can r i n g

and

the

the

removed

by

up due

and

a

part

i s

hence

a

N i c e l y isolated.

to

the

high

l i m i t e d

the

i s

for no

to

r i n g

(33).

isomerase e q u i l i b r i u m

q u a n t i t a t i v e

the

s t a b i l i t y

tendency

compound

pyranose

lack

sugar,

D-fructose

i s w i t h

6-thio-D-glucose

c r y s t a l l i n e The

of of

6-thio-P-D-

l a t e r

nearly from

one

of

the

e s s e n t i a l l y

be

i t s

of

to

substrate

formation

loss.

e a s i l y

When t h e

sodium

of

formation

isomerized

conversion

d i s u l f i d e

work

probably

fructopyranose

i t

becoming

r a t h e r

being

i s

6-thio-D-glucose.

6-thio-D-glucose

general

reversion

another

isomerase

but

fructopyranose

r e d u c t i v e l y

i n t e r e s t i n g transformations

into

from

6-thio-D-fructose established

group

i s

hydrolysis.

attachment

the

i n

which

d e r i v a t i v e .

removed

negative

i n

tosylated.

5,6-epoxide,

tosyloxy

less

i s then

6-0-benzyl

periodate

s u l f u r

3-deoxy-l,2-0-

product

isopropylidene

s u l f u r

uneffected.

to The

o b t a i n

and

the

o x i d i z e d the

by

(32)

This

converted

tosylated

Since

(12)

hydrolyzed

converted


t r e a t e d

and

i s

periodate

s t a r t i n g w i t h

6-0-benzoyl

anion

anion

are

3 - d e o x y - l , 2 : 5 , 6 - d i - 0 - i s o p r o p y l i d e n e - a -

is a

examples

5-thio-D-glucose

removed

isopropylidene-a-D-glucofuranose. the

then then

isopropylidene-a-D-glucofuranose. group

then

shorten-

D-arabinofuranos ide.

route

tosyloxy

may

5 - S - a c e t y l - 3 , 6 - d i - 0 - b e n z y l -

2-deoxy-4-thio-D-riboside r a t h e r

can

or

4-thio-D-arabinoside

synthesis

product

the

which Two

i t

expedient

2-deoxy-4-thio-D-ribose

1,2-0-isopropylidene-5-thio-D-glucofuranose the

the

lengthening

and

i n s e r t i n g

that

structures.

preparation of

remove

for

Therefore

chain

4-thio-D-arabinose

possible as

to

p o s i t i o n

intended

141

into Sugar Rings

Containing Structure

d i f f i c u l t

appropriate

(C-4-thio-g-deoxyribose)


Heteroatoms

WHISTLER AND ANisuzzAMAN

6-thio~-P-D-

of of

s i g n i f i c a n t the

open

to

6 - t h i o - D provide


142


the It

a c y c l i c is

form

fructopyranose than

for

i n t e r e s t i n g

i s

the

enzyme

to

sweetest

note

binding that

sugar

and

i n

There nium

as

routes

the i s

the

Sugar

only

r i n g

known

being

one

example

those

proceeds

α- D - x y l o f u r a n o s e

which to

with

sodium

methanolic

is

diastereomers

of

sugar

analog

The

compound

the

s u l f u r

with

Removal

of

ammonia

chloride

D-threo-3,

phene-2-dimethyl from

nmr

and

Nitrogen An

i n

j o i n i n g

the

the

the

and

gives

syntheses

group the

s t a r t

containing

ment

a

a

sodium

benzyl

mixture

reactions

nitrogen

although of

a

of

desired

often

of

a

of

to

sugar. to

water

solution,

methanolic

methyl

group

In

the

by

before

4:1.

and When

e q u i l i b r a t e s

hydrogen

above

forms

containing

r i n g

group.

can by

Thus

(benzyloxycarbonyl) favor

of

bases

ammonia

u s e f u l

a

a l l

n i t r o

monosaccharide by

i n

d i s p l a c e

the

form

of

w i t h

chloride

the

produces

an

early

i n

methanol

removing

c y c l i z e s

to

the

produce

5-acetamido-5-deoxy-D-

e i t h e r the

was

1,2-0-isopropylidene-

ammonia

form

other the

of

the

compounds be an i f

the

a l t e r e d

is

heated

form.

two

i n

Treatment

r i n g

increase the

amino

pyranose

e q u i l i b r i u m between

i n

favor

i n

the

acetamido group,

form.

Thus

of

forms

as

isopropylidene,

almost

pyranose

l a r g e r

and

n u c l e o p h i l i c i t y

group

the

the is

replaced

e q u i l i b r i u m is

of by

and

nitrogen the

N -

the

s h i f t e d

i n

5-[(benzyloxycarbony1)amino]-5-

deoxy-1,2-0-isopropylidene-a-g-xylofuranose the

a

D-xylosides.

furanose a c y l

established

occurs

reacted

The r e s u l t i n g s u g a r

r a t i o

i t

5-

C-2


along

often S h i f f

(35)

5-acetamido-5-deoxy-D-xylopyranose a

with

Consequently

locate

location

group

Szarek

amino

group.

i n

reduc

monosaccharide

due

h y d r o l y t i c

xylofuranose

two

i s

with

isopropylidene

by

reaction

and

and

the

of

bis(methyl

5-0-p-toluenesulfoyl-a-D-xylofuranose acetylated

Pre

employed.

tosyloxy

and

the

most

reduction

are

i n

designed

a

Jones

s a l t

group

which

compound

carbon

of

Thus,

of

positioned r i n g

at

Displacement method.

i n

carbonyl

hydrazones

analog.

information.

group

or

by

Ring

properly

with

s e l e

prepared

sugar

subsequent

structure

Introduction

reactions

oximes

Sugar

containing i s

4-dihydroxy-2,3,4,5-tetrahydroseleno-

the

spectroscopic

p a r t i c i p a t e s

with

chain.

acetal,

mass

amino

structure

5-[

sweeter

5-Se-benzyl-l,2-0-isopropylidene-5-

l i q u i d

hydrogen

making

reacted

give

i n

a

deoxy-a-D-xylofuranosid-5-yl)-5,5'-diselenide

of

30%

1,2-0-isopropylidene-5-£-p-tolylsulfonyΙ

seleno-a-D-xylofuranose. t i o n

of

(34).

for

from

α-tolueneselenol

i n

some

Ring

heteroatom

to

similar

paration

gen

isomerization.

6-thio-P-D-

D-fructose.

Selenium


necessary

e s p e c i a l l y

e x c l u s i v e l y

gives,

the

on

hydrolysis

c r y s t a l l i n e

(benzyloxycarbonyl)amino]-5-deoxy-Q5-g-xylopyranose

(36)


and

8.

the

six-membered

Amide

I I band For

of

Heteroatoms


r i n g

s t r u c t u r e

i n t h e i r

follows

form

i s

l i k e w i s e

acetamido-5-deoxy-D-xylose. y i e l d s

syrupy


o f a n proportion

compared

w i t h

i n favor

o f

with

o r

a n a c i d

ion-exchange

i n t h e r a t i o

L)-arabinose,

t h e furanose

5 -

5-benzamido-5-deoxy-

c r y s t a l l i n e 5-benzamido-5-deoxy-D-xylopyranose

5-acetamido-5-deoxy-(D

displaced

as

Hydrolysis o f

5-benzamido-5-deoxy-D-xylofuranose

For is

t h e absence

t h e e q u i l i b r i u m

increased,

1,2-0-isopropylidene-a-D-xylofuranose r e s i n

from

143

Rings

spectrum.

5-benzamido-5-deoxy-D-xylose,

t h e pyranose

into Sugar

form.

t h e

Thus,

o f

and 3 : 1 (37).

e q u i l i b r i u m

1,2-0-

isopropylidene-5-0-tolylsulfonyl-P-L-arabinofuranose,

o n

ment

5-acetamido-

with

ammonia

and subsequent

a c e t y l a t i o n ,

y i e l d s

5-deoxy-1,2-0-isopropylidene-P-L-arabinofuranose s i s

o f

t h i s

compound

w i t h

a c i d

gives

(38).

a mixture o f

5-acetamido-5-deoxy-]>arabinopyranose

a n d syrupy

t r e a t Hydroly

c r y s t a l l i n e 5-acetamido-5-

deoxy-L-arabinofuranose. A

s i m i l a r

Azido group

such

r e a c t i o n

i s a good

i s

found

nucleophile

t o proceed t h a t

as p-toluenesulfonyloxy,

a p p l i c a t i o n .

A n example

i s

found

w i t h

r e a d i l y

^-arabinose

displaces

and t h e r e a c t i o n

i n t h e preparation

1,2,3,5-tetra-£-acetyl-4-deoxy-D-xylofuranose,

17.

a

(39).

leaving

has had wide 4-acetamidoReaction

o f

2 , 3 - d i - 0 - b e n z o y l - 4 - (p-tolylsulfonyl) - β - ^ a r a b i n o p y r a n o s i d e , 1 8 w i t h sodium azide g i v e s m e t h y l 4-azido-4-deoxy-a-g-xylopyranoTide, 19

which o n c a t a l y t i c

hydrogénation

3eoxy-a-D-xylopyranoside, a c e t o l y s i s form,

y i e l d s

20.

produces

methyl

N - a c e t y l a t i o n o f

17 a n d p o s s i b l y

a

small

4-amino-4-

19 followed

anount'~~of

i t s

21. ( 4 0 ) .

21

by

pyranose

OAc


144

SYNTHETIC METHODS FOR CARBOHYDRATES The

but

i r spectra

there

i s

no

o f

absorption

a t

rable

t h e furanose

w i t h

Another for

6.5μ.

These

example

absorption

due t o

NH a b s o r p t i o n

a t

and t h e nmr spectra

t h e use o f sugars

o f

amide

17 a r e

displacement nitrogen

r e a c t i o n

as t h e

r i n g

t h e c r y s t a l l i n e

5-acetamido-5-deoxy-a-D-lyxopyranose

22 f r o m

benzyl

2, 3 - £ - i s o p r o p y l i d e n e - 5 - 0 - m e t h y l s u l f o n y l - a - D - l y x o f u r a n o s i d e


In (

J

t h e nmr spectrum o f l

22

2

=

2

·

5

Η ) 2

i s t h e a

Tne

o r i g i n o f

r o t a t i o n

a t

and i s a

r o t a t i o n a l

around

Azide

22 t h e 1 - H s i g n a l s

centered

anomer

o f

has been

i s due t o

also

used

(39),

This

dideoxy-D-xylofuranose L)-arabinofuranose

(42,43), (44),

23

(41).

doublets

indicates

that

22a and22b.

r e s t r i c t i o n o f resonance

o f

t h e

type

f o r t h e preparation

o f

5-benzamido-5-deoxy-D-

(37), 5-acetamido-5-deoxy-D-ribopyranose

5-acetamido-5-deoxy-L-arabinopyranose (and

as

i t s rotamers

r e s u l t i n g from

5-acetamido-5-deoxy-D-xylopyranose xylopyranose

appear

4.09 a n d 4.52.

mixture

isomerism

t £ e C-N b o n d

displacement

τ

I I

compa

~ " azide

containing

i s t h e p r e p a r a t i o n o f

OAc and NAc

3 . Ομ o r

s t r u c t u r e .

o f

t h e p r e p a r a t i o n o f

heteroatom

17 s h o w s

evidenceT"for

(39),

(39)

9

4-acetamido-4,5-

4-acetamido-4-deoxy-D 4-acetamido-4-deoxy-L-xylofuranose


8.

WHISTLER

(45),

Heteroatoms

AND A N i s u z z A M A N

into Sugar

145

Rings

1,2:3,5-di-^-isopropylidene^4-acetamide-4^deoxy-a-L-

xylofuranose

(45) a n d 4 - a c e t a m i d o - l , 2 , 3 ,5 - t e t r a - i O - a c e t y l - D -

ribofuranose

(46).

The

presence

acetamido

group

c o n f i g u r a t i o n

o f

a

i n a

sulfonate

sugar

through

ester

molecule

neighboring

group

i n a d d i t i o n

c a n r e s u l t

group

i n a

t o a n

change

p a r t i c i p a t i o n .

o f

Thus


5-acetamido-5-deoxy--l,2-0-isopropylidene-3-0-methylsulfonyl-Darabinofuranose,

obtained

0-isopropylidene

D-arabinofuranose,~~24,

benzoate

from

5 - 0 - p - t o l y l s u l f o n y l - 5 - d e o x y - l , 2 -

i n N,N-dimethylformamide gives

O-isopropylidene-D-lyxofuranose^25. presumably (47).

proceeds

through

when

heated

w i t h

sodium

5-acetamido~5-deoxy-l,2-

The conversion

t h e o x a z o l i n i u m

o f

24 t o 25

ion-oxazoline

,


system

146

SYNTHETIC

Acid

h y d r o l y s i s o f

5-acetamide

Hydrazine the

o f

i s

The

o f

f i r s t

a

step

involves

d i s p l a c i n g agent A convenient

f o r

method

i n t r o -

(48)

neighboring

which

group

with

s u b s t i t u t i o n o f

by hydrazine t o

form

converts

t h e

t o

f o r i s

the

hydrazine.

the

primary

6-hydrazino-5-

a

three-membered

p a r t i c i p a t i o n .

CH OMs

I

a


group

compound

through

as

sugars.

5-acetamido-5-

1:TT

a n N - a m i n o a z i r i d i n e compound o f hexoses

0-(methylsulfonyl)


u s e f u l

into

CARBOHYDRATES

c r y s t a l l i n e

5, 6 - d i - 0 - ( m e t h y l s u l f o n y l ) a l d o h e x o s e

methylsulfonyloxy r i n g

mixture o f

i n t h e r a t i o

aTio

n i t r o g e n

p r e p a r a t i o n o f

r e a c t i o n

a

FOR

5-deoxy-a-D-Tyxopyranose, 2 6 a n d s y r u p y

deoxy-lyxofuranose,27 duction

25 g i v e s

METHODS

CH -NHNEL

2

H NNH

\£y

MSO-C-H

J,NHNH

I

2

->

MsO-C-H

H

-

C

^

2

R Reduction 5,6-dideoxy d e r i v a t i v e

with

hydrazine

d e r i v a t i v e s which (49).

Thus,

i n presence c a n be

o f

n i c k e l

c y c l i z e d

1, 2 - 0 - i s o p r o p y l i d e n e - 3 , 5 , 6 - t r i - 0 on

r e a c t i o n

t h e isopropylidene

with

group

dideoxy-P-L-idopyranose, form

rated

chromatography

by

t o

pyridine spectra the

o f

29

yield

Reduction a t

o f

i n d i c a t e w i t h

followed

e x i s t s

4 : 1 .

by

h y d r o l y s i s

i n e q u i l i b r i u m

The compound

reacts

w i t h

a c e t i c


t h a t

both

these

s u b s t i t u e n t s

aluminium


to

a t

28

with

i s

sepa-

ariKydride a n d

30.

The nmr

compounds

prefer

C - l and C-5 being

32 a n d a

Hydrolysis

oT^these

from

free

which

hydroxy1

1:1

used

t o

i n

amine,

mixture o f

The nmr spectra

s u l f u r

w i t h

t h e free

amino

t h e

k e t o -

d i m e t h y l sulfoxide and i s

a

dioxide

a r e obtained o f

produce Thus

2 , 3 : 5 , 6 - d i - O - i s o p r o p y l i d e n e - D reduced

gives

l i t h i u m

sugars

derivative^33.

b i s u l f i t e

by r e a c t i o n

t h e p y r r o l i n e

w i t h

4-amino-4-deoxy-D-glucose

4-amino-4-deoxy-D^-galactose w i t h

sugars

i n e q u i l i b r i u m

from

be

molecules.

by o x i d a t i o n with

with a

can a l s o

i n sugar

31 obtained

r e a c t i o n hydride

(50)

l o c a t i o n

dimethyl aceta1

subsequent

e x i s t

and i t

oximes

s p e c i f i c


glucose

xide.

This o f

from

position

groups oxime

28.

prepared

5-(benzyloxycarbonylamino)-5,6-

i t s t r i - O - a c e t y l

C l ( L ) conformation

a x i a l

gives

i n t h e raîfio

28 a n d 3 0

5-amino-

amino-pyranose

(methylsulfonyl-a-D-glucofuranose

benzyloxyformyl c h l o r i d e

furanose

gives

a n

5 - a m i n o - l , 2 - 0 - i s o p r o p y l i d e n e - 3 - 0 -

(methylsulfonyl)-5,6-dideoxy-P-£-idofuranose

of

t o

with

i n d i c a t e

form

and a

adduces

barium

t h a t

hydro-

these

dimeric


form.

WHISTLER AND A N i s u z z A M A N

Heteroatoms

into Sugar Rings


8.

American Chemical Society Library 1155 16th St. N. w. Washington, C. 20036 El Khadem, H.; In Synthetic Methods D. for Carbohydrates; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.

147

148

SYNTHETIC

ÇH(0Me)

.

0

'

\

_

1.

Me S0-Ac

2.

Η N-OH

2

_

^

3

Ο

CARBOHYDRATES

L i A l H ^

3 ( C

0 1

2

C H

3

>2

É-N-0H

i

i-o Downloaded by UNIV OF MICHIGAN ANN ARBOR on February 18, 2015 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/bk-1977-0039.ch008

FOR

ÇH(OMe),

?

-C(CH )

01

METHODS

C ( C H

3

)

> ( C H

2

)

C H / C

H

2 ° 31

CH(OMe),

CH(OMe),

h^x:(CH ) 3

^ C ( C H

2

)

3

2

O•NH

H N2

> C ( C H

)

C H . O ^ 33

Z

CH OH n

I

2

HO-C-H

H-C-OH

OH

1

CH OH 2

-Cj!-OH CH„OH


8.


Heteroatoms

into Sugar

149

Rings

An example o f t h e use o f a hydrazone d e r i v a t i v e t o i n t r o d u c e nitrogen i n t h e sugar r i n g i s t h e preparation 5-acetamido-5-deoxyD - x y l o p y r a n o s e , 34 f r o m 1,2-cyclohexylidene-a-D-xylopentodialdo1 , 4 - f u r a n o s e p h e n y l h y d r a z o n e , 35 ( 5 1 ) . H y d r o g é n a t i o n o f 35 a f f o r d s t h e a m i n o c o m p o u n d , 3 6 w K i c h o n N - a c e t y l a t i o n gives*** 5-acetamido 1,2-p-cyclohexyli3ene-5-deoxy-D-xylofuranose 37. A 2 : 1 m i x t u r e o f 34 a n d i t s f u r a n o s e i s o m e r 38 i s o b t a i n e d b y ^ t h e a c i d hydro lys i s ~ f 37. B o t h 34 a n d 38 a r e a t a b l e i n n e u t r a l solution but readilyêquilibraEe i n acid a t 70°. A benzyl glycos i d e o f 34 consumes two m o l e s o f s o d i u m p e r i o d a t e w i t h t h e l i b e r a t i o n οίΓεΓ m o l e o f f o r m i c a c i d a n d t h i s r e s u l t i s c o m p a t i b l e w i t h a pyranose s t r u c t u r e .


>

OH

5 - A m i n o - 5 - d e o x y - I r - i d u r o n i c 3'9 a c i d r e l a t e d t o t h e c a r b o h y d r a t e component o f p o l y o x i n s h a s ^ e e n s y n t h e s i z e d r e c e n t l y (52). The r e a c t i o n o f 1,2-0-isopropylidene-5-aldo-D-xylopentodialdofuranose w i t h b e n z y l amine a n d hydrogen cyanide" g i v e s 5 - b e n z y l a m i n o 5-deoxy-l, 2-0-isopropylidene^-L-idofuranonitrile, 40, which on hydrolysis with water y i e l d s 5-benzylamino S"-deoxy-l, 2fr-isopropylidene-L-iduronic acid, 41. Hydrogenolysis o f 41 leads t o t h e f o r m a t i o n o f 5-amino-5-deoxy~"compound, 42 from w h i c h t h e f r e e 5 - a m i n o - 5 - d e o x y - L - i d u r o n i c a c i d 39 i s p r e p a r e d by way o f t h e b e n z y l o x y c a r b o n y l compound, 4 3 . TheT"free a c i d 39 e x i s t s i n a e q u i l i b r i u m o f t h e f u r a n o s e "form a n d p i p e r i d i n e H E b r m a n d t h e l a t t e r s i x membered f o r m p r e d o m i n a t e s . : :



150

SYNTHETIC

METHODS

FOR

CARBOHYDRATES

OH Phosphorus i n the Sugar Ring As an exercise i n chemistry and to show the further general i t y of producing sugar rings containing various heteroatoms we undertook the replacement of oxygen by phosphorus i n the six member g-xylose ring (53). i n this sequence, 1,2-0-isopropylidene3-0-methy1-5-0-(p-toluenesulfonyl) c^D-xylofuranose or 5-bromo-5deoxy-1, 2-£-isopropylidene-3-0-methyI-a-D-xylofuranose i s reacted with triethylphosphite to produce the 5-deoxy-5-(diethylphosphinyl) derivative. Reduction with lithium aluminium hydride followed by hydrolytic removal of the isopropylidene group produces i n the one case 5-deoxy-3-jO-methyl-5-phosphinyl-D-xylopyranose, 44 and 5-deoxy-3-£-methyl-5-(phosphinic acid)-D-xylopryanose, 45?~ Formation of 44 and 45 presumably proceed through intermediates 46 and 47. Comûnd 4T"does not mutarotate and i s stable toward a i r oxidation. However, with bromine i t i s oxidized to the phosphinic acid 45. The i r spectrum of 44 shows absorption due to the B-H groupT



8.


Heteroatoms

into Sugar

Rings

151

45 Inokawa and associates recently synthesized a D-ribose deri vative containing phosphorus i n the ring (54). They undertake nucleophilic displacement of the iodo group i n methyl 5-deoxy-5iodo-2, 3-£-isopropylidene-P-g-ribofuranoside with ethyldiethoxyphosphine to produce methyl 5-deoxy-5-(ethoxyethylphosphinyl)-2,3O-isopropylidene-P-D-ribofuranoside 48. Reduction of 48 with sodium dihydro-bis72-methoxyethoxy)'âluminate i n THF gTves methyl 5-deoxy-(ethylphosphinyl)-2,3-0-isopropylidene-P-D-ribofuranoside 49, acid hydrolysis of which yields 5-deoxy-5-(ethylphospinyl)-DrTbopyranose 50. Evidence for the pyranose structure of 50 i s derived from ΈΚβ absence of characteristic PH peaks i n i~Esf nmr and i r spectra. The reaction of 50 with a mixture of acetic anhy dride and pyridine gives i t s 1, 2,3^~4-tetra-0-acetyl derivative, 51 which reverts to 50 on deacetylation with sodium methoxide i n "~ methanol. By using reactions similar to those described above, 5-(alkylphosphinyl)-5-deoxy-3-0-methyl-(and benzyl)-D-xylopyranoses were also prepared (55 56). 5


152

SYNTHETIC METHODS


Ο

FOR CARBOHYDRATES

E t

Literature Cited 1. Ingle, D. L. and Whistler, R. L., J. Org. Chem. (1962) 27, 3896. 2. Schwarz, J. C. S. P. and Yule, K. C., Proc. Chem. Soc. (1961) 417. 3. Adley, T. J. and Owen, L. Ν., Proc. Chem. Soc. (1961) 418. 4. Vegh, L. and Hardegger, E., Helv. Chim. Acta (1973) 56, 2020. 5. Chmielewski, M. and Whistler, R. L., J. Org. Chem. (1975) 40, 639. 6. Zysk, J. R., Bushway, Α. Α., Whistler, R. L. and Carlton, W. W., J. Reprod. Fert. (1975) 45, 69. 7. Graham,T.L. and Whistler, R. L. Biochemistry, (1976) 15, 1189. 8. Gross, B. and Driez, F. X., Carbohyd. Res. (1974) 36, 385. 9. Clayton, C. J. and Hughes, Ν. Α., Chem. Ind. (London) (1962) 1975. 10. Clayton, C. J. and Hughes, Ν. Α., Carbohyd. Res. (1967) 4, 32. 11. Owen, L. N. and Ragg, P. L., J. Chem. Soc. (C) (1966) 1291. 12. Whistler, R. L., Nayak, U. G. and Perkins, A. W., Jr., J. Org. Chem. (1970) 35, 519. 13. Reist, E. J . , Gueffroy, D. E. and Goodman, L., J. Am. Chem. Soc. (1963) 85, 3717.



8. WHISTLER AND ANISUZZAMAN

Heteroatoms into Sugar Rings

14. Reist, E. J . , Gueffroy, D. E. and Goodman, L., J. Am. Chem. Soc. (1964) 86, 5658. 15. Reist, E. J., Fisher, L. V. and Goodman, L., J. Org. Chem. (1968) 33, 189. 16. Cox, J. M. and Owen, L. N., J. Chem. Soc. (C) (1967) 1121. 17. Newth, F. Μ., Advan. Carbohyd. Chem. (1951) 6, 83; Feather, M.S. and Harris, J. F., Advan. Carbohyd. Chem. (1973) 28, 161. 18. Haworth, W. N. and Jones, W. G. M., J. Chem. Soc. (1944) 667. 19. Whistler, R. L. and Hoffman, D. J . , Carbohyd. Res. (1969) 11, 137. 20. Whistler, R. L., Dick, W. E., Ingles, T. R., Rowell, R. M. and Urbas, B., J. Org. Chem. (1964) 29, 3723. 21. Whistler, R. L., Bobek, M. and Bloch, Α., J. Med. Chem. (1970) 13, 411. 22. Ototani, N. and Whistler, R. L., J. Med. Chem. (1974) 17, 535. 23. Stevens, C. L., Glinsky, R. P., Gutowski, G. E. and Dicker son, J. P., Tetrahedron Lett. (1967) 649. 24. Stevens, C. L., Glinski, R. P., Taylor, K. G., Blumbergs, P. and Sirokoman, F., J. Am. Chem. Soc. (1967) 88, 2073. 25. Kefurt, K., Jary, J. and Samek, Z., Chem. Commun. (1969) 213. 26. Nayak, U. G. and Whistler, R. L., J. Org. Chem. (1969) 34, 97. 27. Creighton, A. M. and Owen, L. N., J. Chem. Soc. (1960) 1024. 28. Hall, L. D., Hough, L. and Pritchard, R. Α., J. Chem. Soc. (1961) 1537. 29. Chiu, C-W. and Whistler, R. L., J. Org. Chem. (1973) 38, 832. 30. Whistler, R. L., Luttenegger, T. J. and Rowell, R. M., J. Org. Chem. (1968) 33, 396. 31. Nayak, U. G. and Whistler, R. L., J. Org. Chem. (1968) 33, 3482. 32. Nayak, U. G. and Whistler, R. L., Chem. Commun. (1969) 434. 33. Chmielewski, Μ., Chen, M. S. and Whistler, R. L., Carbohyd. Res., 000. 34. van Es, T. and Whistler, R. L., Tetrahedron (1967) 23, 2849. 35. Jones, J. Κ. N. and Szarek, W. Α., Can. J. Chem. (1963) 41, 636. 36. Paulsen, H., Leupold, F. and Ίodt, Κ., Ann. (1966) 692, 2001. 37. Patel, M. S., Jones, J. Κ. N., Can. J. Chem. (1965) 43, 3105. 38. Jones, J. Κ. N. and Turner, J. C., J. Chem. Soc. (1962) 4699. 39. Hanessian, S. and Haskell, T. H., J. Org. Chem. (1963) 28, 2604. 40. Reist, E. J . , Fisher, L. V. andGoodman, L., J. Org. Chem. (1967) 32, 2541. 41. Brimacombe, J. S., Hunedy, F. and Stacy, M., J. Chem. Soc. (C) (1968) 1811.


153

154 42. 43. 44. 45.


46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56.

SYNTHETIC METHODS FOR CARBOHYDRATES Brimacombe, J. S. and Bryan, J. G. Η., J. Chem. Soc. (1966) 1724. Hanessian, S., Carbohyd. Res. (1965) 1, 178. Dick, A. J. and Jones, J. Κ. Ν., Can. J. Chem. (1968) 46, 425. Dick, A. J. and Jones, J. Κ. Ν., Can. J. Chem. (1965) 43, 977. Reist, E. J., Gueffroy, D. E., Blackford, R. W. and Goodman, L., J. Org. Chem. (1966) 31, 4025. Hanessian, S., J. Org. Chem. (1967) 32, 163. Paulsen, H. and Stoye, D., Chem. Ber. (1969) 102, 820. Paulsen, H. and Friedmann, Μ., Chem. Ber. (1972) 105, 731. Paulsen, Η., Propp, K. and Heynes, Κ., Tettrahedron Lett. (1969) 683. Paulsen, H., Ann. (1963) 670, 121. Paulsen, H. and Mäckel, Ε., Chem. Ber. (1973) 106, 1525. Whistler, R. L. and Wang, C-C., J. Org. Chem. (1968) 33, 4455. Inokawa, S., Kitagawa, H., Seo, K., Yoshida, Y. and Ogata, T., Carbohyd. Res. (1973) 30, 127. Inokawa, S., Ysuyoshi, Υ., Seo, K. and Ogata, T., Bull. Chem. Soc., Japan, (1971) 44, 2279. Seo, K. and Inokawa, S., Bull. Chim. Soc., Japan (1973) 46, 3301.


Methods for Introducing Atoms Other than Oxygen into Sugar Rings

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