Emil Fischer’s proof of the structure of glucose.
1891 (Nobel Prize 1902)
(+)-glucose is an aldohexose
* * * *
CH2-CH-CH-CH-CH-CH=O
OH OH OH OH OH
Four chiral centers  24 = 16 stereoisomers
1
2
3
4
5
6
CH=O
?
?
?
OH
CH2OH
Fischer arbitrarily assigned
the configuration about C-5
to be D.
The structure was verified by
X-ray crystallography in 1951
H
H
H
H
H
H
HO
H
CHO
OH
OH
OH
OH
CH2OH
CHO
OH
OH
H
OH
CH2OH
HO
H
H
H
CHO
H
OH
OH
OH
CH2OH
HO
H
HO
H
CHO
H
OH
H
OH
CH2OH
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
H
HO
HO
H
CHO
OH
H
H
OH
CH2OH
HO
HO
H
H
CHO
H
H
OH
OH
CH2OH
HO
HO
HO
H
CHO
H
H
H
OH
CH2OH
(-)-arabinose is an aldopentose from which (+)-glucose can be
made.
* * *
CH2-CH-CH-CH-CH=O
OH OH OH OH
three chiral centers  23 = 8 stereoisomers
If we artitrarily assign C-4 to be D, then there are 4
stereoisomers
CHO
H
OH
H
OH
H
OH
CH2OH
CHO
HO
H
H
OH
H
OH
CH2OH
CHO
H
OH
HO
H
H
OH
CH2OH
CHO
HO
H
HO
H
H
OH
CH2OH
Fact: oxidation of (-)-arabinose yields an optically active
dicarboxylic acid.
CHO
?
?
H
OH
CH2OH
HNO3
COOH
?
?
H
OH
COOH
optically active
COOH
H
OH
H
OH
H
OH
COOH
meso-compound
optically inactive
COOH
H
OH
HO
H
H
OH
COOH
meso-compound
optically inactive
COOH
HO
H
H
OH
H
OH
COOH
optically active
COOH
HO
H
HO
H
H
OH
COOH
optically active
In (-)-arabinose, the configuration about C-2 must be:
CHO
HO
H
?
H
OH
CH2OH
HNO3
COOH
HO
H
?
H
OH
COOH
optically active
Fact: Using the Kiliani-Fischer synthesis to add a new chiral
center to (-)-arabinose yields a mixture of (+)-glucose and
(+)-mannose.
CHO
HO
H
?
H
OH
CH2OH
K.-F.
CHO
H
OH
HO
H
+
?
H
OH
CH2OH
CHO
HO
H
HO
H
?
H
OH
CH2OH
Fact: Oxidation of both (+)-glucose and (+)-mannose yield
optically active dicarboxylic acids.
H
HO
H
H
COOH
OH
H
OH
OH
COOH
optically active
H
HO
HO
H
COOH
OH
H
H
OH
COOH
meso-compound
optically inactive
HO
HO
HO
H
COOH
H
H
H
OH
COOH
optically active
HO
HO
H
H
COOH
H
H
OH
OH
COOH
opticaly active
The only way that both (+)-glucose and (+)-mannose can
give optically active dicarboxylic acids upon oxidation is
if the configuration about C-4 is with the –OH on the
right in the Fischer projection.
But, which compound is (+)-glucose and which one is
(+)-mannose?
Fact: Oxidation of both (+)-glucose and (+)-gulose yield
the same dicarboxylic acid.
Fact: The dicarboxylic acid produced from (+)-mannose
is not made by the oxidation of any other aldohexose.
HO
HO
H
H
CHO
H
H
OH
OH
CH2OH
(+)-mannose
HNO3
HO
HO
H
H
COOH
H
H
OH
OH
COOH
This oxidation prodct is not made
by the oxidation of any other aldohexose
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
H
HO
H
H
COOH
OH
H
OH
OH
COOH
(+)-glucose
HO
HO
H
H
CHO
H
H
OH
H
CH2OH
(+)-gulose
same compound
HO
HO
H
HO
COOH
H
H
OH
H
COOH
Therefore, (+)-glucose has the following configuration:
C-5 was assigned arbitrarily by Fischer.
1
2
3
4
5
6
H
HO
H
H
CHO
OH
H
OH
OH
CH2OH
C-3 is known from the observation that
the oxidation product of (-) arabinose is
optically active; and (+)-glucose and
(+)-mannose can be made from (-)arabinose by the Kiliani-Fischer
synthesis.
C-4 is known from the fact that both
(+)-glucose and (+)-mannose yield
optically active dicarboxylic acids.
C-2 is known from the fact that both
(+)-glucose and (+)-gulose yield the
same dicarboxylic acid.