Selective substitution at the primary hydroxy group
ethers
esters
Usually, the triphenylmethyl (trityl) ethers are used for the selective O-substitution
at the primary hydroxy groups of saccharides. terc-Butyldimetylsilyl ethers and
pivaloyl esters are often used for the purpose as well. Also toluene-4-sulfonyl
(tosyl) group, if introduced into the saccharide molecule under reduced
temperature and equimolar control, exhibits a significant regioselectivity to the
primary hydroxy group of saccharide in the presence of its unprotected secondary
hydroxy groups.
OTs
OH
OH
O
1 mol TsCl, C5 H5 N
OMe
OH
HO
0 ºC, pyridine
OH
O
OMe
OH
HO
I
NaI, Me2 CO
reflux, 4 h
OH
HO
80 %
methyl α-Dglucopyranoside
O
OMe
OH
95 %
By treatment of methyl α-D-glucopyranoside with one mole of tosyl chloride at
reduced temperature, up to 80 % of its 6-O-tosyl derivative can be obtained.
This can be then transformed by replacement of its 6-O-tosyl group to different
useful 6-substituted D-glucopyranosides, e.g. 6-deoxy-6-iodo derivative (nonanomeric halides of saccharides), but also to 6-amino-6-deoxy derivative
(amino saccharides) or 6-deoxy derivative (deoxy saccharides).
OTs
NH2
OH
HO
O
OMe
OH
NH3, EtOH
OH
HO
H2, Pd/C
O
OMe
OH
N3
NaN3, DMF
OH
HO
O
OMe
OH
Substitutions in situ
Ph3 P + EY
_
-Y
_
+Y
OH
O OMe
OH
18 h, r.t.
HO
OH
ROH
- EH
+
ROP Ph3
Z
RZ + Ph3 P=O
_
+
Ph3 P CX3 X
Ph3 P + CX4
OH
+
Ph3 P E
_
_
+
OP Ph3 X
O OMe
HO
OH
X
OH
O OMe
X = Cl, Br, I
HO
OH
almost quantitative yields
at the primary OH group
(CH3)2C
O CH2
(CH3)2C
O
O
O CH2
O
O
i
Cl
O
HO
O
O
C(CH3)2
O
C(CH3)2
85 %
(CH3)2 C
O CH2
O
O
OH
i
O
O
CH2Cl
O
O
O
(CH3)2C
C(CH3)2
O
O
C(CH3)2
79 %
i: TPP, CCl4, reflux, 96 h
These replacements can be done under convenient steric conditions also at
secondary hydroxy groups, e.g. at the free hydroxy group of 1,2;5,6-di-Oisopropylidene--D-allofuranose. 1,2;5,6-Di-O-isopropylidene--D-glucofuranose
does not fulfil the precondition and gives a rearranged product.
Amino sugars
•
Sugar derivatives with one or more OH groups at their carbon skeletone
(except of hemiacetal OH group  glycosylamines) replaced by a free or
substituted amino group.
OH
OH
OH
O
O
HO
OH
HO
NHAc
N-acetyl-D-glucosamine (GlcNAc,
2-acetamido-2-deoxy-D-glucopyranose),
chitosamine
•
OH
OH
NH2
D-glucosamine (GlcN,
2-amino-2-deoxy-D-glucopyranose),
chitose
Aminosacharidy sa hojne vyskytujú v prírode. N-acetyl-D-glukózamín
(chitózamín) je stavebnou jednotkou polysacharidu chitinu alebo jednou
zo zložiek polysacharidov kyseliny hyalurónovej a heparínu a tiež
mliečnych trisacharidov a vyšších oligosacharidov. N-acetyl-Dgalaktózamín (chondrózamín) je zložkou polysacharidov chondroitín a
dermatán.
Amino sugars
•
Sugar derivatives with one or more OH groups at their carbon skeletone
(except of hemiacetal OH group  glycosylamines) replaced by a free or
substituted amino group.
OH
OH
OH
O
OH
HO
O NH2
HO
NHAc
N-acetyl-D-glucosamine (GlcNAc,
2-acetamido-2-deoxy-D-glucopyranose),
chitosamine
•
OH
OH
-D-glucopyranosylamine
(glycosylamine)
Aminosacharidy sa hojne vyskytujú v prírode. N-acetyl-D-glukózamín
(chitózamín) je stavebnou jednotkou polysacharidu chitinu alebo jednou
zo zložiek polysacharidov kyseliny hyalurónovej a heparínu a tiež
mliečnych trisacharidov a vyšších oligosacharidov. N-acetyl-Dgalaktózamín (chondrózamín) je zložkou polysacharidov chondroitín a
dermatán.
Amino sugars
•
The replacement of an alcoholic hydroxy group of a monosaccharide or
monosaccharide derivative by an amino group is envisaged as substitution of
the appropriate hydrogen atom of the corresponding deoxy monosaccharide by
the amino group. The stereochemistry at the carbon atom carrying the amino
group is expressed by regarding the amino group equivalent to OH.
OH
OH
OH
HO
O
OH
OH
O
OH
HO
NHAc
N-acetyl-D-glucosamine (GlcNAc,
2-acetamido-2-deoxy-D-glucopyranose),
chitosamine
•
NHAc
N-acetyl-D-galactosamine (GalNAc,
2-acetamido-2-deoxy-D-galactopyranose),
chondrosamine
2-Amino-2-deoxysaccharides are abundant in Nature, especially in polysaccharides.
N-acetyl-D-glucosamine (chitosamine) is structural unit of polysaccharide chitin,
or one of structural units of polysacharides hyaluronic acid and heparín. They also
occur in milk trisaccharides and higher oligosaccharides. N-acetyl-D-galactosamine
(chondrosamine) is a component of polysaccharides chondroitin and dermatan.
Chitin (so-called animal cellulose) is main component of
exoskeleton of arthropods
Chitinous
exoskeleton
of insects
(a cikada)
Zdroj: http://academic.brooklyn.cuny.edu/biology/bio4fv/page/struct-carbohydrates.html
http://en.wikipedia.org/wiki/Chitin
It is the main component of the cell walls of fungi, the exoskeletons of
arthropods such as crustaceans (e.g., crabs, lobsters and shrimps) and
insects, the radulas of mollusks, and the beaks and internal shells of
cephalopods, including squid and octopuses.
Bird plumage and butterfly wing scales are often organized into stacks of
nano-layers or nano-sticks made of chitin nanocrystals that produce
various iridescent colors by thin-film interference.
Supramolecular structure of cellulose
n
n
n
http://chemphys.gcsu.edu
Amino saccharides
*
OH
O
O
HO
NHAc
HO
O
NHAc
O
n
*
O
OH
Macromolecule of polysaccharide chitin (poly-(-14-D-GlcNAcp))
*
OH
O
O
HO
OH
OH
HO
O
O
n
*
O
OH
Macromolecule of polysaccharide cellulose (poly-(-14-D-Glcp))
Molecular structure of chitin is very similar to that of cellulose; chitin contains
N-acetyl-D-glucosamine monosaccharide units, cellulose is built up of D-glucose
monosaccharide units. These structural units of both polysaccharides are linked to
each other by β-(1-4)-glycosidic bonds.
Supramolecular structure of cellulose
http://chemphys.gcsu.edu
In addition to basic linear -(14) glycosidic bonds, both intra- and
intermolecular hydrogen bonding occurs in cellulose.
Structural roles of plant polysaccharides
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/struct-carbohydrates.html
Amino saccharides
*
OH
O
O
HO
NHAc
HO
O
NHAc
O
n
*
O
OH
Macromolecule of polysaccharide chitin (poly-(-14-D-GlcNAcp))
*
OH
O
O
HO
OH
OH
HO
O
O
n
*
O
OH
Macromolecule of polysaccharide cellulose (poly-(-14-D-Glcp))
Molecular structure of chitin is very similar to that of cellulose; chitin contains
N-acetyl-D-glucosamine monosaccharide units, cellulose is built up of D-glucose
monosaccharide units. These structural units of both polysaccharides are linked to
each other by β-(1-4)-glycosidic bonds.
Amino saccharides
HOOC
*
OH
O
O
O
HO
O
O
HO
n
*
NHAc
OH
Macromolecule of polysaccharide hyaluronic acid
(poly-(4-D-GlcAp--13-D-GlcNAcp--1))
HO
HOOC
*
OSO3H
O
O
O
O
O
HO
n
OH
NHAc
Macromolecule of polysaccharide chondroitin sulfate
(poly-[4-D-GlcAp--13-D-GalNAc(6-OSO3H)p--1])
*
Amino saccharides
HO3SO
*
O
O
O
OH
O
O
HO
HOOC
n
*
NHAc
OH
Macromolecule of dermatan-sulfate (chondroitin sulfate B)
(poly-[4-L-IdoAp--13-D-GalNAc(6-OSO3H)p--1])
HOOC
O
O
OSO3 H
O
HO
O
O
HO
OH
NHSO3 H
A part of the heparin macromolecule
Structural motifs of the heparin macromolecule
GlcA-GlcNAc
GlcA-GlcNS
IdoA-GlcNS
IdoA(2S)-GlcNS
IdoA-GlcNS(6S)
IdoA(2S)-GlcNS(6S)
Heparin
Native heparin is a polymer with a molecular weight ranging from 3 kDa to
50 kDa, although the average molecular weight of most commercial heparin
preparations is in the range of 12 kDa to 15 kDa. Heparin is a member of
the glycosaminoglycan family of carbohydrates (which includes the closelyrelated molecule heparan sulfate) and consists of a variably-sulfated
repeating disaccharide unit.[5] The main disaccharide units that occur in
heparin are shown below. The most common disaccharide unit is composed
of a 2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine,
IdoA(2S)-GlcNS(6S). For example, this makes up 85% of heparins from
beef lung and about 75% of those from porcine intestinal mucosa.[6] Not
shown below are the rare disaccharides containing a 3-O-sulfated
glucosamine (GlcNS(3S,6S)) or a free amine group (GlcNH3+). Under
physiological conditions, the ester and amide sulfate groups are
deprotonated and attract positively-charged counterions to form a heparin
salt. It is in this form that heparin is usually administered as an
anticoagulant.
http://en.wikipedia.org/wiki/Heparin
Hyaluronic acid (hyaluronan)
Hyaluronan (also called hyaluronic acid or hyaluronate or HA) is an
anionic, nonsulfated glycosaminoglycan distributed widely throughout
connective, epithelial, and neural tissues. It is unique among
glycosaminoglycans in that it is nonsulfated, forms in the plasma
membrane instead of the Golgi, and can be very large, with its molecular
weight often reaching the millions.[2] One of the chief components of the
extracellular matrix, hyaluronan contributes significantly to cell
proliferation and migration, and may also be involved in the progression
of some malignant tumors.
The average 70 kg (154 lbs) person has roughly 15 grams of hyaluronan
in the body, one-third of which is turned over (degraded and synthesized)
every day.[3] Hyaluronic acid is also a component of the group A
streptococcal extracellular capsule,[4] and is believed to play a role in
virulence.[5][6]
Until the late 1970s, hyaluronan was described as a "goo" molecule, a
ubiquitous carbohydrate polymer that is part of the extracellular matrix.[14]
For example, hyaluronan is a major component of the synovial fluid, and
was found to increase the viscosity of the fluid. Along with lubricin, it is
one of the fluid's main lubricating components.
http://en.wikipedia.org/wiki/Hyaluronan
Hyaluronic acid (hyaluronan), contd.
Hyaluronan is an important component of articular cartilage, where it is
present as a coat around each cell (chondrocyte). When aggrecan
monomers bind to hyaluronan in the presence of link protein, large,
highly negatively charged aggregates form. These aggregates imbibe
water and are responsible for the resilience of cartilage (its resistance to
compression). The molecular weight (size) of hyaluronan in cartilage
decreases with age, but the amount increases.[15]
Hyaluronan is also a major component of skin, where it is involved in
tissue repair. When skin is exposed to excessive UVB rays, it becomes
inflamed (sunburn) and the cells in the dermis stop producing as much
hyaluronan, and increase the rate of its degradation. Hyaluronan
degradation products then accumulate in the skin after UV exposure.[16]
While it is abundant in extracellular matrices, hyaluronan also
contributes to tissue hydrodynamics, movement and proliferation of
cells, and participates in a number of cell surface receptor interactions,
notably those including its primary receptors, CD44 and RHAMM.
Upregulation of CD44 itself is widely accepted as a marker of cell
activation in lymphocytes. Hyaluronan's contribution to tumor growth
may be due to its interaction with CD44. Receptor CD44 participates in
cell adhesion interactions required by tumor cells.
http://en.wikipedia.org/wiki/Hyaluronan
Chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a
chain of alternating sugars (N-acetylgalactosamine and glucuronic acid). It is
usually found attached to proteins as part of a proteoglycan. A chondroitin chain
can have over 100 individual sugars, each of which can be sulfated in variable
positions and quantities. Chondroitin sulfate is an important structural
component of cartilage and provides much of its resistance to compression.[1]
Along with glucosamine, chondroitin sulfate has become a widely used dietary
supplement for treatment of osteoarthritis.
Chondroitin sulfate chains are unbranched polysaccharides of variable length
containing two alternating monosaccharides: D-glucuronic acid (GlcA) and Nacetyl-D-galactosamine (GalNAc). Some GlcA residues are epimerized into Liduronic acid (IdoA); the resulting disaccharide is then referred to as dermatan
sulfate.
As part of aggrecan, chondroitin sulfate is a major component of cartilage. The
tightly packed and highly charged sulfate groups of chondroitin sulfate generate
electrostatic repulsion that provides much of the resistance of cartilage to
compression. Loss of chondroitin sulfate from the cartilage is a major cause of
osteoarthritis.
http://cs.wikipedia.org/wiki/Chondroitin_sulf%C3%A1t
Amino sugars
3-amino-3-deoxy-D-glucose (syn. kanosamine) is a
constituent of antibiotics kanamycin and hikizimycin.
O
HO
-Anomer as N-acetyl derivative has m.p. 202 0C and
H2 N
[]D +17  +46 (equilib., water). It can be obtained
OH OH
e.g. from 1,2;5,6-di-O-isopropylidene-3-O-(toluene-4sulfonyl)--D-allofuranose by treatment with NaN3
in DMF, followed by catalytic hydrogenation of 3-azido-3-deoxy derivative and acid
hydrolysis (removal of isopropylidene groups).
HOCH2
5-amino-5-deoxy- D-glucose (syn. nojirimycin), the
H
antibiotic produced by the Streptomyces genus.
N
HO
-Anomer, m.p. 126 0C, []D +100  +73 (equilib.,
HO
water). It can be obtained e.g. via 5-keto- and 5OH OH
oxiimino derivative of 3-O-benzyl-1,2-O-isopropylidene6-O-triphenylmethyl--D-glucofuranose.
The last step, the acid hydrolysis of 5-amino-5-deoxy-1,2-O-isopropylidene--Dglucofuranose is done with sulfurous acid and gived a stable bisulfite aduct, from
which nojirimycin is liberated with an anion exchange resin in the hydroxide form.
HOCH2
Amino sugars
The important property of 4-amino-4-deoxy- and 5-amino-5-deoxyaldoses
is, that their nitrogen atom, being a stronger nucleophile than oxygen of the
hydroxy group, participates in forming the respective furanose ring (more
precisely, the pyrrolidine ring; 4-amino-4-deoxyfuranose), or the pyranose
ring (more precisely, the piperidine ring; 5-amino-5-deoxypyranose).
While L-xylose under the thermodynamic equilibrium preferentially forms
the six-membered ring, 4-amino-4-deoxy-L-xylose preferentially forms the
five-membered ring .
H
CH=O
HO
N
HO
OH
CH=O
OH
HO
H2 N
OH
4-amino-4-deoxyL-xylose
HO
HO
OH
OH
HO
O
HO
OH
OH
4-amino-4-deoxyL-xylofuranose
L-xylose
L-xylopyranose
OH
Amino sugars
If the acetamido group instead of the amino group is linked in the C-4
position to the carbonyl group of an aldose, its weaker nucleophilicity
(compared to that of the amino group) is not sufficient for the
enforcement of the furanose (five-membered) ring and the acetamido
sugar usually and preferentially forms the pyranose (six-membered)
structure.
CH=O
AcHN
HO
OH
AcHN
O
HO
OH
OH
OH
4-acetamido-4-deoxyL-xylopyranose
4-acetamido-4-deoxy-L-xylose
Amino sugars
A more complicated situation occurs in the case of 5-acetamido-5-deoxy aldoses.
These aldose derivatives usually exhibit a more complex thermodynamic
equilibrium of both six-membered piperidine forms and five-membered furanose
forms. The reason is that the reduced nucleophilicity of the acetamido group is
unable to hold the molecule exclusively in the six-membered ring form even though
the ring closure through oxygen produces the less common furanose ring
modification.
CH=O
AcHN
+
H3O
O
OH
(H2SO3)
O
O
Me
Me
Ac
OH
OH
HO
OH
NHAc
5-acetamido-5deoxy-D-xylose
AcHN
N
OH
HO
+
O
OH
OH
OH
OH
dvaparts
diely
two
one part
jeden
diel
5-acetamido-5-deoxy
-D-xylopyranose
5-acetamido-5-deoxy
-D-xylofuranose
Amino sugars
4-Amino-4-deoxy- and 5-amino-5-deoxy sugars are stable in alkaline
solutions. In acidic solutions they rapidly undergo dehydration producing the
respective substituted pyrroles a pyridines.
HO
HO
H
N
OH
5-amino-5-deoxyD-xylopyranose
+
H
N
OH
OH
The reason is the production of stable planar aromatic systems, which
are thermodynamically more stable than non-planar six-membered or
five-membered rings containing all the sp3 atoms.
Deoxy sugars
• Derivatives of monosaccharides with one or more
hydroxy groups (except of the hemiacetal OH group)
replaced with hydrogen atom. Thus they contain in their
carbon chain the methylene groups -CH2- (replacement
of a secondary OH group) or terminal methyl groups CH3 (replacement of a primary OH group).
• If thus the hemiacetal OH group of the cyclic form of
aldose is replaced, such derivatives are anhydro alditols.
Deoxy sugars
O
OH
HO
OH
OH
H3 C
HO
O
HO
H3C
HO
OH
O
OH
OH
OH
2-Deoxy-D-ribose (2-deoxy-D-erythro-pentose)
occurs in all cells as a component of
deoxyribonucleic acid.
L-Rhamnose (6-deoxy-L-manno-hexose) occurs in
bacterial and plant polysaccharides and plant
glycosides. Glycoside quercitrin is a constituent of the
dye quercitron, from which L-rhamnose is isolated after
acid hydrolysis. It can be found in oaks species like the
North American white oak and European red oak.
L-Fucose (6-deoxy-L-galacto-hexose) occurs in plants,
animals and microorganisms. It is a constituent of
different polysaccharides, e.g. natural gums, and also
of maternal milk oligosaccharides and blood group
glycoproteins. Most often obtained by acid hydrolysis of
brown algae fucan.
Blood group antigens
O (or 0) antigen
A antigen
B antigen