Transcript Aldonic acids

Aldonic acids – acyclic derivatives of aldoses
containing in their chain terminal position a carboxyl
group instead of the carbonyl group. They can be
obtained from any aldose by oxidation of its carbonyl
group to carboxyl group. Their names are derived
from the names of original aldoses by changing the
suffix from -ose to -onic acid.
CH=O
H
HO
COOH
OH
H
H
[O]
HO
OH
H
H
OH
H
OH
H
OH
H
OH
CH2OH
D-glucose
CH2OH
D-gluconic acid
Aldonic acids
COOH
OH
OH
OH
Tollens reagent
O
HO
OH
OH
[Ag(NH3)2]+
HO
OH
OH
CH2OH
D-glucose
D-gluconic acid
Br2, H2O
pH 4-6
OH
OH
HO
O
HO
O
O
OH
O
HO
OH
D-glucono-1,5-lactone
OH
D- glucono-1,4- lactone
Why lactones preferentially exist in 5-membered rings
OH
25 °C
COOH
25 °C
OH
O
H2O
91 %
O
COOH
O
O
H2O
9%
27 %
73 %
The reason
O
O
O
+
O
O
O
O
+
O
Lactones, due to their resonance structures, contain two sp2 atoms (carbon C-1
and oxygen ring atom), and thus, their pertinent four ring atoms are placed in a
plane. Therefore the reason is that the five-membered rings much better suit
such planar arrangements than the six-membered rings do.
Uronic acids (syn., glycuronic acids) – derivatives of aldoses containing in
their chain terminal positions an aldehyde group and a carboxyl group.
They can be derived from any aldose by changing its terminal
hydroxymethyl group to carboxyl group. Similarly as aldoses, they normally
exist in cyclic hemiacetal structures. Also similarly as aldonic acids, uronic
acids simultaneously are also forming lactones and in aqueous solutions
form with them equilibrium mixtures. According to the aldose, from which
the uronic acid is derived, is also created its name; e. g., D-glucuronic acid
is derived from D- glucose .
Uronic acids abundantly occur as constituents of plant, animal and
microbial polysaccharides. Methods of their preparation are based on the
oxidation of the primary hydroxyl group of aldoses, reduction of
monolactones of aldaric acids (similar method to the reduction of aldonic
acid lactones to aldoses).
O
OH
OH
OH
O
OH
HO
HO
OH
D-glucose
O
OH
COOH
HO
OH
OH
OH
OH
OH
COOH
OH
OH
OH
O
HO
D-glucuronic acid
HO H O
O
OH
O
H OH
D-glucurono-6,3-lactone
Aldaric acids – derivatives of aldoses, dicarboxylic acids formally derived from any
aldose by oxidation of both terminal groups (aldehydic and primary alcoholic) to
carboxylic groups. Their names are created from the names of original aldoses by
changing their suffix –ose to –aric acid, e. g., D-glucaric acid from D-glucose.
Because of the same functional groups at both ends of their carbon chains, similar
rules are valid for their nomenclature as for alditols. Also total number of their
stereoisomers is lower in comparison with that of aldoses.
They can be prepared from aldoses or aldonic acids by oxidation with nitric acid, or
from uronic acids by oxidation with bromine water.
Similarly as aldonic acids or uronic acids, also aldaric acids form lactones, in some
cases also dilactones (if stereochemical arrangement of their OH groups allows that).
O
COOH
OH
OH
HNO3
HO
H
evaporation
HO
OH
OH
OH
OH
OH
COOH
D-glucose
HO
D-glucaric acid
O
O
O
H
O
OH
D-glucaro-1,4:6,3-dilactone
Saccharinic acids- derivatives of monosaccharides with unbranched or
branched chain, containing a carboxylic group and having a hydroxyl
group substituted with hydrogen atom. Thus, they can be considered
deoxyaldonic acid. There are three isomeric types; saccharinic acids,
isosaccharinic acids and metasaccharinic acids.
Saccharinic acids are built-up at a prolonged treatment of alkaline medium
on monosaccharides (and reducing oligosaccharides) and are products of
the benzil rearrangement of -dicarbonyl derivatives of sugars, which can
be secondary products of the Lobry de Bruyn – Alberda van Ekenstein
isomeization of aldoses or ketoses.
H
H
H
H
COOH
OH
H
OH
OH
OH
Metasaccharinic acid
(3-deoxyaldonic acid)
O
-
+
N Na
S
O
O
Saccharin
Saccharinic acids build-up
_
_
HO
HC
H
O
HC
OH
(MeO) HO
H
(MeO) HO
H
OH
H
OH
H
OH
OH
D-glucose
(3-O-methyl-D-glucose)
(MeO) HO
OH
H
H
OH
H
OH
_
_
- HO (MeO )
OH
enediolate
_
HO
H
OH
C
O
HO
C
O
O
H
O
HO
_
H
H
H
H
H
H
OH
H
OH
H
OH
H
OH
H
OH
H
OH
OH
O
OH
H
OH
O
HC
OH
_
HO
H
HC
_
O
OH
H 2O
_
- HO
C
H
OH
H
H
H
OH
H
OH
OH
OH
benzil rearrangement
O
metasaccharinic
acid
Substitution of the -hydroxyl group to the carbonyl group of aldose or ketose favours the saccharinic
acid build-up, preceeding via -elimination from the enediolate form and providing -dicarbonyl
intermediate necessary for the benzil rearrangement.
Pyruvic acid
COOH
O
OH
H
HO
T
COOH
OH
O
A
AcHN
AcHN
HO
HO
OH
OH
OH
OH
CH2OH
CH2OH
N-Acetyl-D-mannosamine
O OH
COOH
HO
CH3
OH
HO
CH3CONH
O
CH2
O
HO
AcNH
COOH
T
OH
OH
CH2OH
HO NHAc
HOH2C
HO OH
OH
Neuraminic acid (Sialic) (Neu5Ac)
Neuraminic acid is aldolization product of pyruvic
acid and N-acetyl-D-mannosamine
H2
C
COOH
O
T = tautomeization
A = aldolization
= direction of the
substituent orientation
at cyclization
HO
Zanamivir
5-(acetylamino)-4[(aminoiminomethyl)amino]-2,6anhydro-3,4,5-trideoxy-D-glyceroD-galacto-non-2-enonic acid
Active ingredient of Relenza,
the first drug for treatment of
influenza based on the
neuramidinase inhibition
OH
H
O
HO
AcNH
COOH
OH
HO
Neuraminic acid (Sialic acid)
(Neu5Ac)
OH
O
HO
COOH
OH
HO
AcNH
HO
Active ingredient of
protichrípkového lieku Tamiflu,
another drug for treatment of
influenza based on the
neuramidinase inhibition
Neuraminic acid (Sialic acid)
(Neu5Ac)
Reduction of aldoses to alditols
O
OH
OH
OH
OH
O
i
HO
HO
i
HO
OH
i
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
CH2OH
D-glucose
D-glucitol (sorbitol)
D-fructose
i = NaBH4/pH 8 or NaHg/EtOH or H2/Ni/pressure
D-mannitol
Methods of elongation of the carbon chain of
aldoses (Ascent of series)
• Kiliani-Fischer procedure - method of elongation
of the carbon chain of aldoses. Base or acid
catalyzed addition of cyanohydrin to an aldose
aldózu provides a pair of epimeric nitriles of
aldonic acids, which are converted by hydrolysis to
one carbon elonged aldonic acids. These are
converted by evaporation of aqueous solution to
lactones, which are in mild acidic medium solution
reduced with sodium amalgam or at low
temperature with sodium borohydride to the
correcponding aldoses.
Kiliani-Fischer procedure
CN
HCN
CH=O
CN
+
HOCH
R
R
HCOH
R
+
H3O
COOH
COOH
+
HOCH
R
HO
HO
HCOH
R
OH
HO
NaBH4
O
OH
O
OH
D-glucono-1,4-llactone
HO
tautomerization
O
OH
OH
OH
0 °C, pH 3
O
OH
HO
OH
D-glucofuranose
OH
D-glucopyranose
Methods of elongation of the carbon chain of
aldoses (Ascent of series)
• Sowden procedure - method of elongation of the
carbon chain of aldoses. Base catalyzed addition of
nitromethane to an aldose affords nitronic salts of
an epimeric pair 1-deoxy-1-nitroalditols, which can
be transformed to one carbon elonged aldoses by
treatment with a strong acid (usually sulfuric acid,
Nef reaction).
• Two other modifications of the Sowden procedure,
developed at the Institute of Chemistry, Slovak Academy of
Sciences, Bratislava, are using either hydrogen
peroxide/sodium molybdate treatment or ozone treatment of
the nitronate salts, instead of their sulfuric acid treatment.
Sowden procedure
H2SO4 (or H2O2/Na2MoO4 or O3/H2O)
Two other modifications of the Sowden procedure, developed at the
Institute of Chemistry, Slovak Academy of Sciences, Bratislava, are
using either hydrogen peroxide/sodium molybdate or ozone
treatment, instead of sulfuric acid treatment of the nitronate salts.
Aldolization of sugars
dihydroxyacetone
_
qvantitatively
D-glyceraldehyde
D-fructose
D-sorbose
Major products
Aldolization of trioses is
not reverse reaction, as
resulting ketoses are
stabilized by cyclization to
their hemiketal tautomeric
forms.
Cyclic hemiketal forms
of ketoses
D-psicose
D-tagatose
Minor products
Methods of contraction of the carbon chain of
aldoses (Descent of series)
• Wohl degradation - method of contraction of the carbon
chain of aldoses. Starting aldose is by treatment with
hydroxylamine transformed to aldose oxime, which by
treatment with acetic anhydride and sodium acetate
undergoes simultaneous acetylation and dehydration
affording aldononitrile peracetate. Following treatment with
Ag2O in aqueous ammonia causes its deacetylation and
simultaneous elimination of cyanohydrin affording one
carbon shorter aldose. There are several modifications of
the procedure, especially for the last step simplifications,
e.g., by treatment with sodium methoxide in methanol.
• Substantially, this procedure is opposite to the KilianiFischer procedure of elongation of the carbon chain of
aldoses.
Wohl degradation
OH
NH-OH
(CHOH) n
n
OAc
(CHOAc) n
CH 2OAc
B
N
Ag2O
NH 4OH
CH 2OH
(OH)3
(OH)3
N
NaOAc
N-OH
O
OH
CH 2OH
Ac 2O
NH 2OH
O
OH
(CHOH)
OH
OH
O
H
O
(CHOH)
CH 2OH
n
O
O
- AgCN
- AcNH 2
(CHOH)
CH 2OH
OH
n
(CHOH) n-1
CH 2OH
Reciprocity of the Kiliani-Fischer method of aldose carbon chain elongation
and Wohl method of aldose carbon chain contraction
HOCH
R
CN
CN
HCN
CH=O
+
H 3O
HCOH
+
COOH
R
R
HO
COOH
+
HOCH
HCOH
R
R
OH
HO
HO
NaBH 4
O
OH
HO
O
O
OH
(CHOH)
OH
N-OH
O
OH
NH-OH
OH
(CHOH) n
n
OAc
(CHOAc) n
CH 2OAc
B
N
Ag2O
NH 4OH
CH 2OH
(OH)3
(OH)3
N
NaOAc
NH 2OH
O
CH 2OH
Ac 2O
OH
OH
OH
OH
OH
O
HO
OH
O
OH
OH
H
O
(CHOH)
CH 2OH
n
O
O
- AgCN
- AcNH 2
(CHOH)
CH 2OH
OH
n
(CHOH) n-1
CH 2OH
Methods of contraction of the carbon chain
of aldoses (Descent of series)
• Ruff degradation - method of contraction of the carbon chain of
aldoses. Soluble (usually calcium) salts of aldonic acids by
treatment with hydrogen peroxide in presence of ferric ions undergo
oxidative decarboxylation and produce a one carbon shorter aldose.
_
O
C
H
O
·
HO
O
C
-H2O
O
O·
H
OH
R
_
R
Fe2+ + H2O2
R = aldose moiety or aldonic acid moiety
Fe3+
- Fe2+
HC=O
CO2
·
+
Fe3+ + HO + HO-
R
Methods of contraction of the carbon chain
of aldoses (Descent of series)
•
Weerman degradation - method of contraction of the carbon chain of
aldoses. Aldonamide, derived from an aldonic acid, by treatment with
alkaline hypochlorite or hypobromide undergoes the Hofmann
degradation via isocaynate and decomposes to a one carbon shorter
aldose. The new aldose, however, easily undergoes unwanted
oxidation to aldonic acid at the conditions applied (with NaOBr or
NaOCl).
O
O
H
C
NH
HO
NaOBr
O
H
C
N
Br
HO
R
C
_
OH
- HBr
R
R = aldose moiety or aldonic acid moiety
N
R
CH=O
HO
- CO2
HO
NH 2
H 2O
R
- NH 3
R