Carbohydrate acetals and ketals

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Carbohydrate acetals and ketals

• Two types of structurally different derivatives
  of carbohydrates. The acetal (or ketal) group of
  the first type of carbohydrate acetals (ketals)
  originates from a carbonyl group of any carbonyl
  compound and two hydroxyl groups of carbohydrate
  (e. g., 2,3-O-isopropylidene-D-glyceraldehyde (I)
  from acetone and D-glyceraldehyde). The second
  type originates from a carbonyl group of a sugar
  and two hydroxyl groups of any alcohol (e. g.,
  D-glyceraldehyde dimethyl acetal (II) from
  D-glyceraldehyde and methanol).
• .

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Carbohydrate acetals and ketals
Also glycosides are sugar acetals (derived from
aldoses) or ketals (derived from ketoses), e. g.,
methyl a-D-glucopyranoside (III), but also
internal glycosides, e. g., 1,6-anhydro-?-D-glucop
yranose (IV) (red colour shows the acetal
functional group).
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Carbohydrate acetals and ketals

• Acetone, benzaldehyde, acetaldehyde and
  formaldehyde are most often employed carbonyl
  compounds for preparation of ketals and acetals
  of the first type.
• According to these starting carbonyl compounds,
  they are called as isopropylidene ketals
  (1,25,6-di-O-isopropylidene-?-D-glucofuranose,
  1,2-O-isopropylidene-?-D-glucofuranose,
  1,23,4-di-O-isopropylidene-?-D-galactopyranose),
  and benzylidene (4,6-O-benzylidene-D-glucopyranose
  ), ethylidene and methylene acetals of
  carbohydrates.

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• 1,25,6-di-O-isopropylidene-?-D-glucofu
  ranose (I)
• (obsolete name, diacetone glucose) crystalline
  compound, m. p. 110 C, ?D -180 (water),
  soluble in water and many organic solvents. The
  acid hydrolysis rate of its 5,6-O-isopropylidene
  group is 40-times higher than that in position
  1,2. This is employed for preparation of another
  important derivative, 1,2-O-isopropylidene-?-D-glu
  cofuranose (II). Ketal I is employed as starting
  compound in many syntheses. Thus, e. g., the
  intermediates, obtained either after oxidation of
  its free hydroxyl group to 3-oxo derivative, or
  after its O-substitution, are employed for
  preparation of aminosaccharides, deoxysaccharides
  or branched-chain saccharides.

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• 1,23,4-di-O-isopropylidene-?-D-galactopyranose
• Is employed in synthesis of saccharides and their
  derivatives, e. g., D-fucose (6-deoxy-D-galactose
  ) or D-galacturonic acid.

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• Carbohydrate acetals and ketals are stable in
  basic and neutral solutions. In acid solutions
  they decompose to the starting sugar and carbonyl
  compound. Their hydrolysis rate is highest for
  benzylidene acetals and decreases in the order
  isopropylidene ketals, ethylidene acetals and
  methylene acetals. From carbohydrate benzylidene
  acetals, the saccharide can be regenerated also
  by hydrogenolysis on paladium, similarly as from
  benzyl ethers.

D-fucose (6-deoxy-D-galactose)
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4,6-O-benzylidene-D-glucopyranose (I)
40 of 4,6-O-benzylidene-D-glucopyranose (I) can
be isolated by reacting D-glucose with 1 mol of
benzaldehyde. An excess of benzaldehyde gives
rise to 1,24,6-di-O-benzylidene-a-D-glucopyranose
(II).
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Nowadays, more modern, transacetalization
(transketalization) reagents are employed for
preparation of carbohydrate acetals and ketals
acetone dimethyl ketal instead of acetone and
benzaldehyde dimethyl acetal instead of
benzaldehyde.
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Conformational analysis of the carbohydrate
ketals and
acetals
Ketones (R1-CO-R2), reacting with hydroxyl groups
of carbohydrates, preferentially provide the
termodynamically more favourable five-membered
cyclic ketals of the 1,3-dioxolane type. The
characteristic examples are O-isopropylidene
ketals (R1 R2 Me).
The reason is that both the bulky substituents
R1, R2 are placed in equivalent, degenerated
quasi-equatorial (or quasi-axial) positions.
Aldehydes (R-CHO), reacting with hydroxyl groups
of carbohydrates, preferentially provide the
termodynamically more favourable six-membered
cyclic ketals of the 1,3-dioxane type. The
characteristic examples are O-benzylidene acetals
(R Ph).
In this case, the bulky substituent Ris placed
in equatorial position andhydrogen atom in the
axial position.
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Isopropylidene ketals of common aldohexoses
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In case of employing more modern
transketalization reagent, acetone dimethyl ketal
instead of acetone, D-mannose does not afford
1,25,6-di-O-isopropylidene-?-D-mannofuranose,
but its glycoside, methyl 1,25,6-di-O-isopropylid
ene-?-D-mannofuranoside.
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Acetals and ketals of alditols
D-glucitol (sorbitol)
2,4-O-benzylidene-D-glucitol
1,32,45,6-tri-O-benzylidene-D-glucitol
1,32,4-di-O-benzylidene-D-glucitol
1,25,6-di-O-izopropylidén-D-manitol alebo 1,23,4
5,6-tri-O-izopropylidén-D-manitol
(rôzne podmienky)
D-manitol
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Acetals and ketals of alditols
D-glucitol (sorbitol)
1,32,45,6-tri-O-benzylidene-D-glucitol
1,25,6-di-O-isopropylidene-D-mannitol or 1,23,4
5,6-tri-O-isopropylidene-D-mannitol
Acid (differentcondition)
(rôzne podmienky)
D-mannitol
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Synthetic employment of carbohydrate acetals and
ketals
2,4-O-benzylidene- D-glucitol
L-xylose
D-allose
1,25,6-di-O-isopropylidene-
?-D-glucofuranose
1,25,6-di-O-isopropylidene-
?-D-allofuranose
Free sugars can be practically released from all
sugar acetals or ketals by hydrolysis with a 3 N
strong acid at room temperature within 48 hours.