The Structural Properties of the Anomeric Center in Pyranoses and

4 The Structural Properties of the Anomeric Center in Pyranoses and Pyranosides G. A. JEFFREY

Downloaded by UNIV OF ROCHESTER on September 24, 2016 | http://pubs.acs.org Publication Date: January 25, 1979 | doi: 10.1021/bk-1979-0087.ch004

Department of Crystallography, University of Pittsburgh, Pittsburgh, PA 15260

The anomeric carbon atom, C-1, in pyranose and furanose sugars is unique in that it is the only carbon atom in these molecules which is bonded to two atoms which are more electronegative. These more-electronegative atoms necessarily have lone-pair electrons. It is the electronic structure which arises from the electronegativity differences and the presence of these lone-pair electrons that gives rise to the special reactivity and structural properties of the anomeric carbon center. In this paper, we will be concerned with the molecular geometry, as described by the torsion angles, bond lengths and valence angles associated with the anomeric carbon atom in α and ß pyranosyl compounds, I and II. The Pauling

C - l —

(I)a-D

H

I

X

"electronegative difference" (1) between the anomeric carbon, C - 1 , and the ring oxygen O-5 on one side and the aglycon, X, on the other, leads to a depletion of electrons at the carbon atom; the C-O and C-X σ-bonds are polarized in the direction of the more electronegative atoms. Pauling's rule (1) concern ing the "essential electronegativity of atoms" then requires that there be some compensatory electronic shift to re-establish the balance of nuclear and electronic charge in the region of the central carbon atom. This is achieved by a "back-donation" of electrons from the lone-pair orbitals of the flanking oxygen and 0-8412-0470-5/79/36-087-050$05.00/0 © 1979 American Chemical Society

Szarek and Horton; Anomeric Effect ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

4.

Properties

JEFFREY

X atoms

of the Anomeric

t o w a r d s the c a r b o n a t o m .

lone-pair

orbitals

a non-bonding

T h e e l e c t r o n d e n s i t y of

of X i s r e d u c e d i n o r d e r

O—C

(J* o r b i t a l ,

f r o m the l o n e - p a i r

orbitals

s i m i l a r l y the

C - X orbital.

r e l a t i o n s h i p s of the 2p a t o m i c o r b i t a l s are

involved are

differences

different for

i n the e n e r g i e s


there are

also

energy

"back-donate

S i n c e the

a n d the C - O a n d

C - X there

and bond dimensions between When X is a glycosidic

and structural

the

sub-

differences

between different

conformational isomers

sidic bond.

electronic perturbation from ideal electron-

This

r e l a t i v e to the

glyco-

p a i r b o n d i n g w i l l be g r e a t e s t w h e n the h e t e r o - r i n g a t o m i s most electronegative

divalent atom,

i . e.

most electronegative monovalent atom, sequence,

the " a n o m e r i c

effect" was

Chu and L e m i e u x ( 2 J when ation was

the m a j o r

fluorides.

A

oxygen, i . e.

the

and X is

fluorine.

In

the con-

f i r s t c l e a r l y identified by

they o b s e r v e d

that the ( X - c o n f i g u r -

p r o d u c t i n the p r e p a r a t i o n of p y r a n o s y l

remarkably

perceptive publication by E d w a r d s

h a d p r e v i o u s l y p o i n t e d out the i m p o r t a n c e of the s p a t i a l m e n t of the o x y g e n l o n e - p a i r s differences

as a b a s i s for

( .3 )

arrange-

explaining

the

i n s t a b i l i t y t o a c i d h y d r o l y s i s o f a a n d |3 m e t h y l

pyranosides. When X is a hydroxyl or glycosidic group, i n t e r a c t i o n w i t h the c a r b o n p o r b i t a l s , non-bonding orbital,

observed (4)

conformations in pyranoses effect

),

(j5

bond.

In

This

the a n o m e r i c

w h e r e the e l e c t r o n e g a t i v e effects

c r y s t a l s t r u c t u r a l w o r k o n t h e 1,

small,

s h o u l d be l e s s

the

important Some

5-dithio-ribopyranosides

s t u d i e d this a s p e c t of

a t o m e l e c t r o n i c s t r u c t u r e i n contexts other than The most generally

the " g a u c h e - e f f e c t " , the u n e x p e c t e d

effect.

difference

(6^).

Other investigators have c h e m i s t r y ( _7-9_).

state "exo"

a l t h o u g h it i s b a s i c a l l y a m a n i f e s t a t i o n of

and e x o - a n o m e r i c

this v i e w

are

effect h a s b e e n c a l l e d the

a n d p r o b a b l y n o n - e x i s t e n t i n 1, 5 - d i t h i o - p y r a n o s i d e s . supports

the

consequence,

b e t w e e n the r i n g h e t e r o - a t o m a n d c a r b o n i s v e r y anomeric

lone-pair

i n v o l v e d i n the

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

the s a m e a s p e c t of e l e c t r o n i c s t r u c t u r e as In 5 - t h i o - p y r a n o s e s ,

the

r e l a t i v e to t h e g l y c o s i d i c b o n d

and pyranosides

and in solution ( £ ) .

anomeric

which are

i s s e n s i t i v e to t h e t o r s i o n a n g l e o f

glycosidic C - l — O - H or C - l — O-R preferred

hetero-

carbohydrate

accepted descriptor

is

o r i g i n a l l y p r o m p t e d b y the n e e d to e x p l a i n

'gauche'

c o n f o r m a t i o n o f f l u o r o m e t h a n o l ( 10

).

T h e s a m e type of c o n f i g u r a t i o n a l a n d c o n f o r m a t i o n a l d i r e c t i n g properties

1 1

spatial

the a a n d B c o n f i g u r a t i o n s ,

a a n d (3 c o n f i g u r a t i o n a l i s o m e r s . stituent,

electron

electrons

of the r i n g o x y g e n w i l l

into a c o r r e s p o n d i n g non-bonding

the

to i n c r e a s e t h a t o f

t h e r e b y i n c r e a s i n g the

d e n s i t y i n the r e g i o n of the c a r b o n ;

bonds

51

Center

c a n be a n t i c i p a t e d , for

example,

i n the

carboranes


ANOMERIC E F F E C T

52

c o n t a i n i n g the b o n d i n g s e q u e n c e f l a n k e d b y two o r m o r e deficient in electrons

C~B—C,

electronegative

s i n c e the b o r o n a t o m i s atoms,

to f i l l i t s o w n 2 s a n d 2 p

while

being

orbitals.

Q u a n t u m - m e c h a n i c a l d i s c u s s i o n s of the " g a u c h e a n d the " a n o m e r i c

and e x o - a n o m e r i c

effect" have

p u b l i s h e d ( 1 0 - 13 ) w h i c h p r o v i d e a m o r e

a n d the e l e c t r o s t a t i c

b e t w e e n the v i c i n a l l o n e - p a i r

electrons.

The


c o m p l e t e d e s c r i p t i o n of

these electronic interactions,

anomeric

most conspicuous

effect

sidic bonds.

repulsions

structural consequences

a r e i n the c o n f o r m a t i o n a l a n g l e s

of

of the

the

glyco-

T h e change in potential energy with rotation

the g l y c o s i d i c b o n d s

(Figure

mechanical methods

(J_3

later i n this a r t i c l e ,

s u g g e s t that t h e r e a r e

2 to 5 k . c a l / m o l e . angles

effect"

been

) o n the m o d e l c o m p o u n d s

In c o n s e q u e n c e ,

lie within quite n a r r o w

pyranosides

( L4

).

This

about

1) c a l c u l a t e d b y a b - i n i t i o q u a n t u m -

the g l y c o s i d i c

ranges

for

discussed

energy b a r r i e r s

the m e t h y l a

anomeric conformational

of

torsion and 0

energy

p o t e n t i a l w i l l a l s o a p p l y to the g l y c o s i d i c l i n k a g e - b o n d s

i n the

(l-»n)

in many

linked oligosaccharides

and its effect i s o b s e r v e d

of the d i - a n d t r i s a c c h a r i d e s w h i c h h a v e b e e n s t u d i e d b y c r y s t a l structure analysis

( 12^).

It s h o u l d b e i n c l u d e d i n t h e

ational potential-energy maps

of p o l y s a c c h a r i d e s

conform-

containing

such

linkages. More-subtle pyranoses

differences

and pyranosides

also occur between a

i n the b o n d l e n g t h s

and 0

and valence

a s s o c i a t e d w i t h the h e m i - a c e t a l a n d a c e t a l m o i e t i e s . small

struc tural differences

affect

the o v e r a l l d i m e n s i o n s of a m o n o s a c c h a r i d e

degree,

of l e s s

than 5 p m and 5

do not

to a

large

but w h e n m u l t i p l i e d i n a l i n e a r p o l y s a c c h a r i d e

t h e y c o u l d l e a d to s i g n i f i c a n t d i f f e r e n c e s i n t e r p r e t the s o m e w h a t f r o m oriented fibres into account these

polymer,

i n the m o d e l s

used

m a r g i n a l X - r a y diffraction data

and gels.

T h e u s e of a v e r a g e d

dimensions for m o n o s a c c h a r i d e

components,

small differences,

i n the i n t e r p r e t a t i o n of f i b r e

diagrams

angles

These

to

available

molecular

w h i c h do not take

c o u l d l e a d to

ambiguities

b y the m o d e l - b u i l d i n g

methods. More chemistry,

importantly,

f r o m the p o i n t of v i e w of t h e o r e t i c a l

these s m a l l differences

provide an

c r i t e r i o n w i t h w h i c h to t e s t the " n e a r n e s s particular assumes

excellent

to r e a l i t y " o f a

"ab-initio" quantum mechanical calculation.

This

that the b e s t t h e o r e t i c a l t r e a t m e n t i s that w h i c h

the b e s t a g r e e m e n t

w i t h the s t r u c t u r a l d a t a ,

of a n o v e r - s i m p l i f i c a t i o n .

which is

gives

somewhat

S o m e of the w a v e f u n c t i o n s u s e d

the a b - i n i t i o c a l c u l a t i o n s a r e

b e l i e v e d to g i v e

reliable

in

values



4.

JEFFREY

Properties

of the Anomeric

Center

Figure 1. Theoretical potential-energy curves for rotation about the anomeric bond from ah initio Hartree-Fock 431-G calculations on dimethoxymethane. $ is the glycosidic 0-5-C-l-0-l-CH torsion angle. is the C-5-0-5-C-1-0-1 torsion angle and is ~ 60° for a-D-pyranosides, ~ 180° for f3-D-pyranosides (see Figure 2). :{


53

54 for

ANOMERIC E F F E C T

energies,

but p o o r g e o m e t r y ;

lengths but less w i l l be

others give reliable

reliable bond angles.

The most

the c o m p a r i s o n of the a c t u a l o b s e r v e d

Significant

t o w a r d the e x p e r i m e n t a l

a t i o n of e l e c t r o n d e n s i t y d i s t r i b u t i o n s i n m o l e c u l e s as carbohydrates

by c r y s t a l diffraction


The Experimental

determin-

as

complex

methods.

Data

T h e r e i s n o w a s i g n i f i c a n t a m o u n t of e x c e l l e n t s t r u c t u r a l data on p y r a n o s e obtained by

molecular

sugars and m e t h y l pyranosides

' s t a t e of the a r t '

X - r a y and neutron-diffraction

crystal-structure determinations.

A l l the r e s u l t s q u o t e d h e r e i n

were obtained f r o m t h r e e - d i m e n s i o n a l diffractometer ments.

The atomic parameters,

than 4%.

The more

measure-

w h i c h include those

the a n i s o t r o p i c t h e r m a l m o t i o n of the a t o m s , full-matrix least-squares better

test

and calculated

electron-density distribution i n these m o l e c u l e s . p r o g r e s s is now being m a d e

bond

sensitive

methods accurate

were

to a g r e e m e n t structure

describing

refined

factors

by

of

determinations

also included c r y s t a l X - r a y or neutron absorption and extinction corrections.

In a f e w

of these p r e c i s e

bond lengths w e r e c o r r e c t e d for however,

structure analyses,

rigid-body

the

thermal motion;

for c o n s i s t e n c y and b e c a u s e of s o m e

uncertainty

c o n c e r n i n g the s i g n i f i c a n c e of t h e s e t h e r m a l m o t i o n c o r r e c t i o n s , we

have

r e p o r t e d the u n c o r r e c t e d v a l u e s

T h e full data for

i n the f o l l o w i n g

tables.

the i n d i v i d u a l s t r u c t u r e d e t e r m i n a t i o n s

b e e n p u b l i s h e d e l s e w h e r e ( 13_).

In T a b l e s

I,

II,

III,

p r e s e n t a s u m m a r y of these

results in a f o r m

c o m p a r i s o n w i t h the r e s u l t s

of t h e o r e t i c a l a b - i n i t i o

have

and IV,

suitable

we

for

molecular

o r b i t a l c a l c u l a t i o n s a i m e d at p r e d i c t i n g the m o l e c u l a r

geometry

of the h e m i - a c e t a l a n d a c e t a l m o i e t y i n p y r a n o s e s

pyrano-

sidic

and

molecules. The experimental standard deviations for individual

structure determinations are lengths

a n d 0 . 1° i n a n g l e s .

neutron analyses

is comparable,

involving hydrogen atoms. bond lengths, atoms

observed of ~ 1 p m ,

for

of 0. 5 p m i n b o n d

except for

the

we

and

dimensions

O n l y i n the n e u t r o n w o r k a r e

valence and torsion angles involving

accurate

In the t a b l e s

of the o r d e r

T h e a c c u r a c y of the X - r a y

e n o u g h to be

relevant for c o m p a r i s o n with

g i v e the e x t r e m e

values

a n d the m e a n

each bond length and valence angle.

there i s no r e a s o n

theory.

value

A t the

level

to e x p e c t that the b o n d l e n g t h s

v a l e n c e angles w i l l be i d e n t i c a l f r o m m o l e c u l e b e c a u s e none of the p y r a n o s e

the

hydrogen

and

to m o l e c u l e ,

ring conformations is exactly


the

4.

Properties

JEFFREY


Table I.

XPERIMENTAL Methyl

Methyl

studies)*

a-pyranoaides

(3 N e u t r o n

studies)^

0-5

-

C- 1

a-D-Pyranosides

O 1 —

/\

C H

145. 0

142. 1

141. 1

144.2

114. 3

112. 9

113. 0

141.8 143.54

141. 3

111. 5

111. 3

113. 5

141.63

139. 1 140.44

142. 3

Mean

1 4 3 . 05

113. 4

112. 3

113. 1

Max.

143. 9

141. 8

140. 1

142. 2

114. 3

113. 0

114. 0

Min.

142.8 143.53

141. 3

140. 0

140. 7

113. 5

112. 0

113. 9

141.57

140. 07

141. 70

113. 9

112. 5

113. 9

144. 2

114. 7

111. 9 109. 8 111. 2

118.9 111.4

144. 1

142. 7

142. 8

143. 0

140. 8

139.8

142. 3

113. 2

Mean

143.44

141. 80

140.75

143. 48

114. 1

a - Linkages

143. 7

141. 1

142. 2

142.9

116. 0

(2 N e u t r o n s t u d i e s ) —

143.4

140. 3

141.4

141. 9

144.4

142. 3

(142.3)

(144.4)

studies)-

H E O R Y -

—M e t h y l a-arabinoside

/ \

O-l

C-l

Min.

Max. Min.

(5 X - r a y

/ \

C-5

3

Max.

Mean a-Linkages

55

Center

Acetal Geometry in Methyl

C-5

a-pyranosides

(8 X - r a y

of the Anomeric

and m e t h y l

tt-xyloside,

molecules

1 and 2 [Jeffrey,

G.

A.

115. 0 114. 3

113. 8

110. 9 110. 7

115. 9

114. 0

(115.9)

and T a k a g i , S. ,

117.8

(1977),

unpublished work. ] Methyl a-glucoside

[Berman,

Methyl a-galactoside

4-Deoxy-4-fluoro Commun.

[Gatehouse, [Gatehouse,

a n d K i m , S.

Crystallogr.

4,

24,

897.]

B.

M.

and Poppleton,

B.

J . , Acta Crystallogr.

(1971),

B27,

654.]

M.

and Poppleton,

B.


(1970),

B26,

1761. J

M.

and Poppleton, [Choong,

and m e t h y l a - m a n n o s i d e

B.


W. , Stephenson.

N.

(1971), B 2 7 ,

C . , and Stevens,

871.]

J . D. , C r y s t .

B33,

[Poppleton,

—excludes a-linkages

Isomaltulose

B.

[Jeffrey,

J . , Jeffrey,

G.

G.

A.,

A.,

McMullan,

and W i l l i a m s ,

w h i c h f o r m p a r t of C - O - C - O - C - O - C s e q u e n c e of [Chu,

[Dreissig,

Planteose

(Rohrer,

D.

Raffinose

(Berman,

H.

Melezitose

[Horotsu,

S. S.

W.

C.

and Jeffrey,

and L u g e r ,

P.,

M. ,

Acta C r y s t a l l o g r .

and S h i m a d a ,

A.,

Pople,

J. A.,

A.,

(1972), (1970),

S. , C h e m .

—6 - M a l t o s e [ C r e s s , M . E . a n d J e f f r e y , G . S u c r o s e [ B r o w n , G . M . and L e v y , H. A . , G.

G.

R.

G.

K. , and T a k a g i ,

S. ,

Acta

J . B. , Acta Crystallogr.

bonds.

Acta Crystallogr.

Acta Crystallogr.

C. , Acta Crystallogr. K.

Struct.

728.]

2400.]

- M e t h y l 8-maltoside

1 Jeffrey,

(1968),

491.]

(1977),

Methyl a-altroside

H. , Acta Crystallogr.

B. B.

methyl a-glucoaide

(1975),

—Methyl a-glucoside

B31,

M.

[Gatehouse,

Methyl a-mannoside Methyl a-altroside

H.

B28,

(1973),

B29.

23,

1038.]

514).

425.]

B26,

290.]

L e t t e r s (1973),

p. 8 3 . ]

A . , A c t a C r y s t a l l o g r . (1977), A c t a C r y s t a l l o g r . (1973), B 2 9 ,

a n d B i n k l e y , S. , J . A m e r .

(1967),

C h e m . Soc.

^90]. 790.]

(1978), 100,

373].


(1975),

56

ANOMERIC EFFECT


Table II.

EXPERIMENTAL Methyl

Methyl

C- 5

8-pyranosides

(8 X - r a y

Acetal Geometry in Methyl /?-D-Pyranosides

studies)-

0-6

C-lI

C-l

CH

Ob

3

C-l

OA

107. 1

114. 4

Max.

144.2

143.7

143. 4

Min.

142.6

142. 1

139. 3 137. 4

112.7

142. 1

110. 6

108. 1

Mean

143.29

142.81

138.29

142.70

111.4

107.9

112. 4 113. 4

142. 1

142. 7

138. 1

142. 6

111.1

107. 4

113. 0

Max.

144.8

142. 7

139. 7

144.

1 12. 2

107. 7

117. 3

Min.

143. 6

142. 5

138.4

143. 6

111.2

Mean

144. 13

142.60

138.93

144.10

111.9

106.9 107. 4

116. 4

B-xylo-

pyranoside (Neutron

study) —

8 - Linkages (3 X - r a y s t u d i e s ) -

- M e t h y l (a-L)-arabinoside Methyl B-xyloside

[Jeffrey.

[Brown.

Methyl 8-giucoside Methyl 8-galactoside

C.

[Jeffrey, [Jeffrey.

6 - 0 - A c e t y l methyl B-giucoside 6 - 0 - A c e t y l methyl B-galactoside

A. G.

[Chu,

S.

S.

and T a k a g i .

A.

S. . ( 1 9 7 7 ) ,

G . . and L l e w e l l y n .

and T a k a g i .

[Lindberg,

K. K.

[Lindberg,

C and Jeffrey,

F.

unpublished

J. . J . Chem.

S. . A c t a C r y s t a l l o g r .

and T a k a g i ,

[Lindberg.

3,4-Ethylidene methyl 0-galactoside Methyl 0-maltoside

G. A.

J . , Cox,

G.

t>

B. .

S. . A c t a C r y s t a l l o g r . Acta C r y s t a l l o g r .

G.

(1976),

B. . Acta C r y s t a l l o g r . A.,

Acta C r y s t a l l o g r .

(1966).

B33.

p. 9 2 2 . ]

738.1

( 1 9 7 8 ) , B3jt, 20O6J.

(1976),

B. , Acta C r y s t a l l o g r . K.

work.] Soc.

(1977).

115. 8

B32.

642.]

B32,

(1976), (1967),

645.]

B32. 23,

639. ]

1038.)

b Takagi,

S.

and Jeffrey,

G.

A.,

Acta Crystallogr.

(1977),

in

press.

-Cellobiose [ C h u , S. S. C . a n d J e f f r e y , G . A . , A c t a C r y s t a l l o g r . (1968), 24, 8 3 0 . ] G a l a c t o - L - r h a m n i t o l [ J e f f r e y , G . A . a n d T a k a g i , S. . A c t a C r y s t a l l o g r . ( 1 9 7 7 ) , 1£3_, 2 3 7 7 ] . a-Lactose-H20 [ F r i e s , D. C . , R a o . S. T . , and S u n d a r a l i n g a m , M . . A c t a C r y s t a l l o g r . (1971), -Jeffrey,

G.

A. , Pople,

J . A . , and B i n k l e y , S. , J . A m e r .

Chem.

Soc.

(1978), 100.

27.

373.


994.]

57

Properties

of the Anomeric

Table III.

11 em i-acetal Geometry in a-D-Pyranoses

JEFFREY

4.

Center


EXPERIMENTAL a-Pyranoses (10 X - r a y

a-

studies)-

Pyranoses

(3 N e u t r o n s t u d i e s ) —

Max. Min.

148. 1

144. 7

142. 1

115. 5

113. 1

142. 6

141. 2

138.2

112. 1

110.9

Mean

144.48

142.77

138.52

113. 7

111.9

Max.

143. 9

142. 5

140. 4

114. 7

111.9

Min.

142. 7

141. 8

113. 4

109. 8

Mean

143. 20

142.07

138.9 140. 03

97.9 95. 2 9 6 . 63

113. 9

111. 1

108. 1

144. 4

142. 1

141. 7

(109.5)

(109.5)

(109.5)

THEORY

-a-D-Xylose

(Morild,

B-D, L-Arabinose

E . , private communication;

[Kim,

S.

B-L-Arabinose

[Hordvik,

a-D-Galactose

[Ohanessian,

Acta Crystallogr. a-Fucose B31,

tt-D,

Hordvik,

A.,

Scand.

IS,

(1961),

J . and G i l l i e r - P a n d r a u d , B32,

A.,

Acta Chem.

Acta C r y s t a l l o g r . H. ,

Scand.

(1967),

22^

(1971),

25,

2175.]

537.]

16.]

Acta Crystallogr.

(1976),

B32,

2810;

Sheldrick, B. ,

1016.]

F. , Ohanessian,

J . , Avenel,

D. , a n d N e u m a n ,

A.,

Acta Crystallogr.

(1975),

[Killean,

R.

C.

G. ,

Lawrence,

J . L . . and S h a r m a ,

V.

C. , Acta Crystallogr.

(1971),

1707.]

August,

[Planinsek,

F . and R o s e n s t e i n ,

R.

D. ,

Abstr.

N10,

American Crystallogr.

Assoc.

Meeting,

1967. ]

a-D-Mannose, B32,

Acta C h e m .

G.

2623. ]

L-Mannose

a-Talose

A.,

(1976).

[Longchambon,

a-L-Rhamnose-H20 B27,

H . and Jeffrey,

( 9 6 . 0)

109. 2 107. 4

molecules

1 and 2

[Longchambon,

F. ,

Avenel,

D. , and N e u m a n ,

A.,

Acta Crystallogr.

(1976),

1822.] [Ohanessian,

b a-D-Glucose -

[Brown,

J., G.

Avenel,

M.

B-L-Arabinose

[Takagi,

S.

a-L-Rhamnose

[Jeffrey,

G.

D. , K a n t e r s ,

and L e v y , and A.

H.

Jeffrey.

G.

and T a k a g i .

Table IV.

A., A.,

J. A.,

and S m i t s ,

S c i e n c e (1965),

D. , A c t a C r y s t a l l o g r .

147,

Acta Crystallogr.

B33,

(1977),

B3J., 3 0 3 3 ] .

2551.]

Hemi-acetal Geometry in /?-r>Pyranoses

C-l -JL_ . c

liH

E X P E R I M E N T A L

0-5

C-l

8 -Pyranoses

Max.

144. 0

143. 3

139.9

112. 7

107. 2

(5 X - r a y

Min.

142. 6

141.3

138.4

111.9

106. 2

Mean

143. 40

1 4 2 . 52

139.36

112.0

106. 8

142.4

139. 8

(109.5)

(109.5)

atudies)-

—0 - L - L y x o s e

[Morild,

0-D-Glucose

[Chu,

B-D-Galactose Avenel,

D.,

S.

1063.]

1038.]

( 1 9 7 8 ) , B3k,

S. , (1977),

(1977),

E . , private communication. ] S.

[Sheldrick,

C.

and Jeffrey.

B. ,

and N e u m a n ,

G.

A.,

Acta Crystallogr. A.,

Acta Crystallogr. (1976),

Acta Crystallogr.

2-Deoxy-2-fluoro-B-D-mannose [Choong, W. , C r a i g , C r y s t a l S t r u c t . C o m m u n . (1975), 4, 111.]

B32.

(1975), D.

(1968),

1016;

B31,

24,

830.]

Longchambon,

F.,

Ohanessian,

2623.]

C . , Stephenaon,

N.

C . , and Stevens,


J . D. ,

J .

58

ANOMERIC EFFECT

same.

T h e y a r e a l l d i s t o r t e d to a g r e a t e r

the i d e a l

C i conformation,

4

or lesser

degree

i n p a r t b y the i n t r a m o l e c u l a r

actions between substituent h y d r o x y l groups

and in part

c r y s t a l - f i e l d effects.

Because

c h a i r i s not a

flexible

s o m e bond lengths and angles

r i n g ( 1 5 , 16 ),

the p y r a n o s e

d i f f e r e n t w h e n the r i n g c o n f o r m a t i o n a l a n g l e s T h e m o s t obvious

feature

are

from

inter-

by

must

be

different.

of the e x p e r i m e n t a l d a t a o n the

a a n d |3 p y r a n o s e m o l e c u l e s i s t h e s h o r t e n i n g o f t h e

anomeric


C - l — O H b o n d l e n g t h f r o m a n o r m a l v a l u e o f 1 4 2 . 5 p m to 139 to 140 p m .

The C - l — 0 - 5

the 0 - 5 — C - 5 differences

bond is

b o n d l e n g t h h a s the n o r m a l v a l u e ,

143-144 p m .

the a n o m e r i c c a r b o n a t o m , 113.8 and 111.5°,

at the r i n g o x y g e n ,

C-l.

s i g n i f i c a n t l y l e s s i n the 0 - a n o m e r s ,

i . e.

t h a n t e t r a h e d r a l i n the 3

112 a n d 1 0 7 ° .

the f r e e

sequence

are both longer

The C - l — 0 - 5

than n o r m a l ,

angles,

that at the c a r b o n a t o m i s l e s s

both oxygen angles

are greater

than

In the m e t h y l a - p y r a n o s i d e s , the s h o r t e s t of the f o u r 1 p m less.

C - O bonds,

markedly

bond is

of the O - O - C - O — C

normal,

acetal

143-144 p m ,

significantly different f r o m each other.

marked

config-

The methyl

sugars in having a

s h o r t g l y c o s i d i c b o n d o f 139 p m . and the two e x t e r n a l C—O b o n d s

angle

there is a

b e t w e e n the two

urations i n both bond lengths and valence angles. resemble

There

valence bond

in contrast,

i n the m o l e c u l a r g e o m e t r y

g -pyranosides

angles

are

pyranoses.

In the m e t h y l p y r a n o s i d e s , difference

a n d at

these

w h e r e a s they

i s d e f i n i t e e v i d e n c e that the 0 - 5 — C - l — O - l is less

molecules CMS,

In the a s u g a r s ,

respectively,

and

significant

o b s e r v e d b e t w e e n the a a n d 0 p y r a n o s e

a r e i n the v a l e n c e - b o n d a n g l e s are

The only

but not

O f the t h r e e

valence

than tetrahedral,

while

tetrahedral. the g l y c o s i d i c b o n d i s but the d i f f e r e n c e

The bond-shortening appears

is

to be s h a r e d

more

e q u a l l y b e t w e e n the two C - O b o n d s

o n e i t h e r s i d e of the

carbon.

the e x t e r n a l C - O b o n d s

A s i n the | 3 - p y r a n o s i d e s ,

acetal sequence valence angles C-l

are are

the l o n g e s t .

The differences

s i m i l a r to the 8 a n o m e r s ,

value is t e t r a h e d r a l r a t h e r than less T h e d a t a r e l a t i n g t o t h e a-

observed in di-

b e c a u s e of the

a n d the p o o r e r

available.

of the

b e t w e e n the

e x c e p t that the

and 0-linkages

c o m p l e x i t y of t h e i r s t r u c t u r e s ,

the c r y s t a l s that a r e g e n e r a l l y

anomeric

than t e t r a h e d r a l .

a n d t r i s a c c h a r i d e s t e n d to b e l e s s p r e c i s e , greater

still about

T h e r e i s no

q u a l i t y of evidence

that the s u b s t i t u t i o n of a s u g a r r e s i d u e f o r a m e t h y l r e s u l t s significant differences bonding.

i n the s t r u c t u r e of the a c e t a l

We have included only those acetal sequences

are flanked by C—C bonds

in

C - O - C - O - C which

and have omitted f r o m this listing


4.

Properties

JEFFREY

of the Anomeric

t h o s e that f o r m p a r t of a l o n g e r C—O bond sequences raffinose

Center

c h a i n of C - O b o n d s ,

as i n a , a - t r e h a l o s e ,

and m e l e z i t o s e .

59

sucrose,

i . e.

seven

planteose,

T h e data on these compounds

have

b e e n p u b l i s h e d e l s e w h e r e ( 12 ). The

neutron-diffraction results are in good agreement

the X - r a y d a t a f o r trend for

the C - O b o n d l e n g t h s a n d a n g l e s .

t h e C - O b o n d l e n g t h s to b e a b o u t

observed by neutron diffraction.


observed analyses believe

have been made

1 p m shorter

This has been

in studies where both X - r a y and o n the s a m e

a

when

generally

neutron-diffraction

c o m p o u n d ( 1 7 - 1 9 )•

that this effect i s r e a l a n d i s a c o n s e q u e n c e

that the t h e r m a l l y s m e a r e d

with

T h e r e is

We

of the

fact

e l e c t r o n d e n s i t y of the o x y g e n

atoms

i s d i s p l a c e d a w a y f r o m the n u c l e a r c e n t e r i n the d i r e c t i o n of the lone-pair

electrons,

t h e r e b y t e n d i n g to i n c r e a s e

C - O bond lengths and d e c r e a s e The

the

observed

O valence

angles.

Theoretical Calculations The

theoretical calculations with which these

data c a n be c o m p a r e d a r e CH3OCH2OH

(12,)

the p y r a n o s e analogy

Figure

experimental

b a s e d o n the u s e of m e t h o x y m e t h a n o l

and d i m e t h o x y m e t h a n o l C H 3 O C H 2 O C H 3

as m o d e l compounds for The

the o b s e r v e d

and methyl pyranoside molecules, to t h e p y r a n o s e s

and pyranosides

in

respectively.

is illustrated in

2.

The

c a l c u l a t i o n s w e r e c a r r i e d out u s i n g the a b - i n i t i o

Hartree-Fock 431-G basis-set Ditchfield,

Hehre,and Pople

s h o w n that the p r e f e r r e d

m o l e c u l a r o r b i t a l m e t h o d of

( 2£).

Energy calculations

have

c o n f o r m a t i o n s f o r t h e (X- a n d

w e r e the + s c , + s c a n d ap, +sc

( 1 2 , 13 ),

and only these conformations w e r e c o n s i d e r e d .

experimental data,

models,

3-

anomers

respectively

180° f o r

In the

the t o r s i o n a n g l e C - 5 — 0 - 5 — C - l — C - l

n e c e s s a r i l y c l o s e to 60° f o r the a c o n f i g u r a t i o n , by ± 5 °

( 1_3 )

the h e m i - a c e t a l a n d a c e t a l m o i e t i e s

is

and close

t h e (3 c o n f i g u r a t i o n ( t h e y v a r y f r o m t h e s e i d e a l

s i n c e the p y r a n o s e

glycosidic torsion angles pyranoses

r i n g s a r e not i d e a l

chairs).

l i e b e t w e e n 70 a n d 1 0 0 ° f o r

a n d b e t w e e n 60 a n d 80° f o r

the m e t h y l

to

values

the

The

free

pyranosides.

T h e s e v a l u e s h a v e b e e n r e p o r t e d e l s e w h e r e ( 1 1 , 12 ). In the m e t h o x y m e t h a n o l m o d e l o n l y the C - O b o n d were varied. angles

w e r e m a i n t a i n e d at t e t r a h e d r a l v a l u e s In the d i m e t h o x y m e t h a n o l m o d e l ,

a n d the 0-5^ The

+ s c , +sc

lengths

T h e C - H b o n d l e n g t h s w e r e f i x e d at 96 p m a n d a l l

C-l,

and O - l

( 12 ).

both C - O bond

valence angles

lengths

w e r e v a r i e d ( 13 ).

conformation is s y m m e t r i c a l , and therefore


only


ANOMERIC EFFECT


4.

Properties

JEFFREY

of the Anomeric

two b o n d l e n g t h s a n d two a n g l e s model,

for

the P p y r a n o s i d e s ,

three variable

HI,

and


For

are possible.

The values

of

w h i c h o p t i m i z e the

shown under

E x p e r i m e n t and

the a a n d 3 p y r a n o s e

THEORY

energy

in Tables

C~5 — O-B

s u g a r s , the c a l c u l a t i o n s

> 0-5-—C~l

f u l l y p r e d i c t e d b y the t h e o r y .

> C-l —O-l

In t h e g p y r a n o s e

closely

is

success-

case,

the

b e t w e e n t h e o r y a n d e x p e r i m e n t i s w e l l w i t h i n the

experimental error calculates ~ 2

limits.

p m longer

w h i c h i s not o b s e r v e d valence angles

F o r the a c a s e ,

t h a n the $,

the g l y c o s i d i c

but this s m a l l

experimentally,

also been

structural features a t i o n s (_13 )•

could disappear

h a d the

optimized.

is m o r e

important because

of the

is again v e r y good.

than 2 p m in m o s t c a s e s .

The

theoretical values

for

those observed.

the v a l e n c e a n g l e s

are

The biggest difference

e x p e r i m e n t i s the t h e o r e t i c a l o v e r - e s t i m a t e a n g l e b y 3° i n b o t h c a s e s .

This agreement

calculdifference

reproduced i n the

i n the s a m e

sense

between theory

and

of the C - l

valence

s h o w s that the

ab-initio H a r t r e e - F o c k 431-G approximation, well-chosen models,

is

The differences

when used

c a n g i v e v e r y g o o d d e s c r i p t i o n s of

h e m i - a c e t a l a n d a c e t a l m o i e t i e s of the s u g a r m o l e c u l e s , as p r e d i c t i n g m o l e c u l a r

geometry.

t h i s w i l l a p p l y to a l l m o l e c u l e s

not i m p o r t a n t .

that the s u b s t i t u t i o n of a p r i m a r y a n d s e c o n d a r y on C-5

i n s t e a d of two h y d r o g e n s

changes

with the as

It i s a f a i r a s s u m p t i o n

involving first-row

where d-orbital interactions are

the

more

which w e r e optimized in these later

The agreement

i n the b o n d l e n g t h s b e t w e e n the two c o n f i g u r a t i o n s

as

bond

discrepancy,

T h e c o m p a r i s o n b e t w e e n the d i m e t h o x y m e t h a n e a n d a and p pyranosides

to b e t t e r

I,

Theory

the s h o r t e n i n g of the g l y c o s i d i c b o n d v e r y

a n d the s e q u e n c e agreement

+sc and

IV.

C o m p a r i s o n Between

reproduce

In the a p ,

variable bond lengths

and valence angles

of the m o d e l m o l e c u l e s a r e II,

c a n be v a r i e d .

four

valence angles

these bond lengths

61

Center

far that

elements

It a l s o alcohol

suggests group

does not m a k e any v e r y

major

i n the e l e c t r o n i c s t r u c t u r e of the C ~ O - C - 1 — O - C

bonds.

T h i s i s c o n s i s t e n t w i t h the c h e m i c a l e x p e r i e n c e anomeric

that the

effect i s a p a r t i c u l a r p r o p e r t y o f the a n o m e r i c

which applies

to a l l p y r a n o s e s

and pyranosides

and is

i n s e n s i t i v e to t h e c o n f i g u r a t i o n a t t h e n o n - a n o m e r i c

general center

relatively

carbon

atoms. This 21794,

r e s e a r c h was

supported by Grants

U.S. Public Health Service,

G M - 1 1 2 9 3 and

G M -

N a t i o n a l Institutes of H e a l t h .


62

ANOMERIC EFFECT


Literature Cited (1) Pauling, L., "Nature of the Chemical Bond," pp. 88, 273, 3rd Edit., Cornell University Press, Ithaca, 1960. (2) Lemieux, R. U. and Chü, Ν. J., Abstracts of Papers, Amer. Chem. Soc. (1958) 133, 31N. (3) Edwards, J. T., Chem. & Ind. (London) (1955) p. 1102. (4) Jeffrey, G. A . , Pople, J. A. and Radom, L., Carbohydr. Res. (1972) 25, 527. (5) Lemieux, R. U . , Pure & Appl. Chem. (1971) 25, 527. (6) Girling, R. and Jeffrey, G. Α . , Acta Cryst. (1974) B30, 327. (7) de Hoog, A. J., Buys, H. R . , Altona, C. and Havinga, Ε., Tetrahedron (1969) 25, 3365. (8) Romers, C., Altona, C., Buys, H. R. and Havinga, Ε., Topics Stereochem. (1969) 4, 39. (9) Wolfe, S., Rank, Α . , Tel, L . M. and Csizmadia, I. G . , J. Chem. Soc. (1971) B, 136. (10) Wolfe, S., Accts. Chem. Res. (1972) 5, 102. (11) Jeffrey, G. A., Pople, J. A. and Radom, L., Carbohydr. Res. (1972) 25, 117. (12) Jeffrey, G. A., Pople, J. A. and Radom, L., Carbohydr. Res. (1974) 38, 81. (13) Jeffrey, G. A., Pople, J. A . , Binkley, S. and Vishveshwara, S., J. Amer. Chem. Soc. (1978), 100, 373. (14) Jeffrey, G. A. and Takagi, S., Acta Cryst. (1977) B33, 738. (15) Sachse, Η . , Berichte (1890) 23, 1363. (16) Dunitz, J. D. and Waser, J., J. Amer. Chem. Soc. (1972) 94, 5645. (17) Brown, G. M . and Levy, Η. Α . , Acta Cryst. (1973) B29, 790. (18) Jeffrey, G. A., McMullan, R. K. and Takagi, S., Acta Cryst. (1977) B33, 728. (19) Takagi, S. and Jeffrey, G. Α . , Acta Cryst. (1977) B33, 3033. (20) Ditchfield, R . , Hehre, W. J. and Pople, J. A., J. Chem. Phys. (1971) 54, 724. RECEIVED September

27, 1978.


The Structural Properties of the Anomeric Center in Pyranoses and

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