1. (guest lecture by Prof. F. E. Ziegler)
Title
Lecture 72, April 24, 2010
The Carbohydrates
[C(H2O)]n
(guest lecture by Prof. F. E. Ziegler)
extracted from
Emil Hermann Fischer ( )

2. F-R Convention The Fischer-Rosanoff Convention CHO C2-OH C3-OH C4-OH
C6-CH2OH

3. D/L Series Fischer-Rosanoff D- and L-Series
OH on the right of the highest
numbered chiral carbon = D-series.
OH on the left of the highest
numbered chiral carbon = L-series.

4. D-Aldohexoses The D-Aldohexoses 2 right 8 right 2 left C3 2 right
Allose
Altrose
Glucose
Mannose
Gulose
Galactose
Idose
Talose
All altruists gladly make gum in gallon tanks [L. Fieser]

5. Rxn of Aldoses Reactions of Aldoses osazone CHO OH CH2OH + PhNH2 + NH3
=N-NHPh
CH2OH OH
osazone OH HO
CHO
CH2OH
3 equiv. PhNHNH2
CO2H OH
aldaric acid HO
HNO3
achiral
alditol OH
CH2OH
NaBH4 HO
achiral
CO2H OH
CH2OH
aldonic acid
Br2/H2O HO

6. Osazones More on Osazones CHO OH CH2OH HO D-glucose OH CH2OH HO
D-fructose O OH HO
CHO
CH2OH
D-mannose
Ca(OH)2
(Lobry de Bruyn-
Alberda van Eckenstein
rearrangement, 1895)
3 equiv.
PhNHNH2
1 equiv.
PhNHNH2
=N-NHPh OH
CH2OH HO
D-glucose phenylhydrazone OH HO
=N-NHPh
CH2OH
D-mannose
phenylhydrazone
1 equiv.
PhNHNH2
+ PhNH2 + NH3
2 equiv.
PhNHNH2
=N-NHPh
CH2OH OH HO

7. F-K and Ruff Chain Lengthening and Shortening of Aldoses OH HO CN
CH2OH
HCN
Fischer-Kiliani
Synthesis OH
CH2OH
CHO
Fe+++
H2O2
Ruff
Degradation
Pd/BaSO4
pH 4.5, H2
CHO OH
CH2OH HO
CO2Ca1/2 OH
CH2OH HO
Br2/H2O
Aldonic acid as Ca salt

8. D-Series Interrelationship
Interrelationship of the D-Series of Aldoses
via Chain Lengthening and Degradation

9. Which one is Glucose? The Aldohexoses But which one is (+)-glucose?
D-series
L-series

10. Aldaric Acids/Alditols
Rosanoff Formulation of C6 Aldaric Acids and Alditols
Terminal groups identical; CO2H or CH2OH

11. Fischer Proof: 1 X Fischer’s Proof: Part 1
(+)-Glucose forms an optically active aldaric acid and optically active alditol.
1, 7, 9, 15 eliminated: plane of symmetry, achiral X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

12. Fischer Proof:2 X X Fischer’s Proof: Part 2
(+)-Glucose and (+)-mannose form the same osazone. If 1, 7, 9, and 15
are not related to (+)-glucose, then they are not related to (+)-mannose nor
are 2, 8, 10, and 16 related to (+)-glucose. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 X X

13. Fischer Proof:3 Fischer’s Proof: Part 3
(+)-Arabinose affords (-)-glucose and (-)-mannose by Kiliani-Fischer synthesis.
(+)-Arabinose must be of the opposite series (D/L)as (+)-glucose and have the
same absolute configuration at C3-5 as (-)-glucose and (-)-mannose.
What is the structure of arabinose?

14. F P:3, con’t X Arabinose is either or
(+)-Glucose is one of these structures
Arabinose forms an optically active
aldaric acid (arabinaric acid)
and optically active alditol
(arabitol)
Arabinose is

15. Fischer Proof:4 X Fischer’s Proof: Part 4
The pentose (+)-xylose affords optically inactive xylaric acid and optically
inactive xylitol as its borax complex.
(+)-Xylose can only be one of the following: X
These enantiomers cannot be (+)-xylose because their Fischer-Kiliani hexoses
(already eliminated) would lead to one optically active and one optically
inactive aldaric acid.
Fischer-Kiliani synthesis of (+)-xylose leads to two new hexoses, (+)-gulose
and (+)-idose, both of which form optically active aldaric acids.
(+)-Xylose must be one of the remaining two structures.

16. Fischer Proof:5 Fischer’s Proof: Part 5 (+)-Arabinose
(+)-Xylose
(+)-Gulose/(+)-Idose
(+)-Glucose/(+)-Mannose

17. or Fischer Proof:5, con’t Fischer’s Proof: Part 5
(+)-Glucose and (-)-gulose form the same
optically active aldaric acid, glucaric acid.
identical or
(+)-Glucose must be either
identical

18. Fischer Proof:5, con’t-2 Fischer’s Proof: Part 5
(+)-Mannose must be one of these hexoses,
the C2 epimer of (+)-glucose.
rotate 180o
identical
mannaric acid
rotate 180o
identical
Mannaric acid is formed from
a single hexose.

19. Fischer Proof:6 Fischer’s Proof: Part 6
But which enantiomer of glucose is (+)-glucose?
D-glucose
L-glucose
Just Guess!
Fischer arbitrarily assigned the D-series to the dextrorotatory enantiomer.
Sixty years later (1951), he was proved correct when Bijvoet
related (+)-glucose to (+)-tartaric acid.
Fischer: All sugars related to D-(+)-glucose by chemical correlation
belong to the D-series.

20. Fischer’s Flaw A Flaw in the Fischer Scheme
(+)-Glucose
(-)-Glucose
(-)-Galactose
(+)-Galactose
Identical
Achiral
Mucic Acid
(An Aldaric Acid)
"Two aldoses can produce the same dibasic acid only if they belong to the same
stereochemical family. That this, however, is erroneous as a general proposition,
may be readily seen from the fact that the two enantiomorphous galactoses - plainly
belong to the opposite families - yield the same mucic acid.” A. M. Rosanoff-1906

21. Rosanoff’s Wheel Rosanoff’s Reorganization of the Carbohydrates
Arranged by successive Kiliani
syntheses
The D- and L- assignments were
Fischer’s based on chemical
correlation with D-(+)-glucose,
an unreliable scheme. 2 4 8 16
-series
-series
mirror plane

22. Evolution of Signage Evolution of Signage Optical Activity
Configuration
Fischer-1891
+/-
d,l
Rosanoff-1906
+/-

Today
+/- = d,l
D,L

23. D-Aldohexoses The D-Series of Aldoses aldotriose aldotetrose aldo
(+)-glyceraldehyde
(+)-threose
(-)-erythrose
(-)-ribose
(-)-arabinose
(+)-xylose
(-)-lyxose
(+)-altrose
(+)allose
(+)-glucose
(+)-mannose
(-)-gulose
(-)-idose
(+)-galactose
(+)-talose
aldotriose
aldotetrose
aldo
pentose
aldo
hexose
All altruists gladly make gum in gallon tanks [L. Fieser]

24. Fischer Projections Fischer Projections of Glucose CHO OH HO CH2OH CHO3 4 5
CHO OH
HOH2C HO =
rotate C5 about C4 by 120o
form hemiacetals between
C5-OH and C1
D-(+)-Glucose

25. Anomers Fischer Projections of Glucopyranose Anomers right alpha left
beta HO C C OH OH OH HO HO OH OH O O
CH2OH
CH2OH
b-D-(+)-Glucopyranose
a-D-(+)-Glucopyranose

26. The End
The
End