relies on pulling of the equilibrium by (irreversible) decarboxylation of the formed
α-amino-β-hydroxycarboxylic acid catalyzed by a decarboxylase to yield the
corresponding aminoalcohols as final products [1600].
2.4.2 Thiamine-Dependent Acyloin and Benzoin Reactions
In the aldol reaction, C–C coupling always takes place in a head-to-tail fashion
between the umpoled Cα atom of an enolate- or enamine-species (acting as donor)
and the carbonyl C of an acceptor forming a β-hydroxycarbonyl product. In
contrast, head-to-head coupling of two aldehydic species involving both carbonyl
C atoms would lead to α-hydroxycarbonyl compounds, such as acyloins or benzoins. For this reaction, one aldehyde has to undergo umpolung at the carbonyl C,
which is accomplished with the aid of an intriguing cofactor: thiamine diphosphate
(ThDP, Scheme 2.193) [1601–1604]. This cofactor is an essential element for the
formation/cleavage of C–C, C–N, C–O, C–P, and C–S bonds and plays a vital role
as vitamin B 1 [1605–1607]. A schematic representation of the mechanism of
enzymatic carboligation by ThDP-dependent enzymes is depicted in Scheme
2.193 [1608]. In a first step, ThDP is deprotonated at the iminium carbon, leading
to a resonance-stabilized carbanion. The latter performs a nucleophilic attack on an
aldehyde (R
1 –CH¼O), which is converted into the donor by forming a covalently
bound carbinol species bearing a negative charge, equivalent to an enamine. This
umpoled species attacks an acceptor aldehyde (R
2 –CH¼O) going in hand with C–C
bond formation. Tautomerization of the diolate intermediate releases the α-ketol
(acyloin/benzoin) product and regenerates the cofactor. Overall, the net reaction
constitutes the transfer or an acyl anion equivalent to an aldehyde.
NH 2
N
N
O
H
S
N
S
N
OH
R
1
S
N
O
H
R 1
O
H
R 2
H
N
S
O
R
2
H
R 1
O
R 2
H
OH
R
1
O
Thiamine Diphosphate
= Phosphate
+ H +
Ylide
Activated Aldehyde
Donor
Umpolung
Acceptor
Coupling
*
*
* newly generated stereocenter
Release of
Product
Acyloin
P
P
P
C-C
- H +
Scheme 2.193 Thiamine diphosphate-dependent carboligation of aldehydes (acyloin reaction)
218
2 Biocatalytic Applications
α-amino-β-hydroxycarboxylic acid catalyzed by a decarboxylase to yield the
corresponding aminoalcohols as final products [1600].
2.4.2 Thiamine-Dependent Acyloin and Benzoin Reactions
In the aldol reaction, C–C coupling always takes place in a head-to-tail fashion
between the umpoled Cα atom of an enolate- or enamine-species (acting as donor)
and the carbonyl C of an acceptor forming a β-hydroxycarbonyl product. In
contrast, head-to-head coupling of two aldehydic species involving both carbonyl
C atoms would lead to α-hydroxycarbonyl compounds, such as acyloins or benzoins. For this reaction, one aldehyde has to undergo umpolung at the carbonyl C,
which is accomplished with the aid of an intriguing cofactor: thiamine diphosphate
(ThDP, Scheme 2.193) [1601–1604]. This cofactor is an essential element for the
formation/cleavage of C–C, C–N, C–O, C–P, and C–S bonds and plays a vital role
as vitamin B 1 [1605–1607]. A schematic representation of the mechanism of
enzymatic carboligation by ThDP-dependent enzymes is depicted in Scheme
2.193 [1608]. In a first step, ThDP is deprotonated at the iminium carbon, leading
to a resonance-stabilized carbanion. The latter performs a nucleophilic attack on an
aldehyde (R
1 –CH¼O), which is converted into the donor by forming a covalently
bound carbinol species bearing a negative charge, equivalent to an enamine. This
umpoled species attacks an acceptor aldehyde (R
2 –CH¼O) going in hand with C–C
bond formation. Tautomerization of the diolate intermediate releases the α-ketol
(acyloin/benzoin) product and regenerates the cofactor. Overall, the net reaction
constitutes the transfer or an acyl anion equivalent to an aldehyde.
NH 2
N
N
O
H
S
N
S
N
OH
R
1
S
N
O
H
R 1
O
H
R 2
H
N
S
O
R
2
H
R 1
O
R 2
H
OH
R
1
O
Thiamine Diphosphate
= Phosphate
+ H +
Ylide
Activated Aldehyde
Donor
Umpolung
Acceptor
Coupling
*
*
* newly generated stereocenter
Release of
Product
Acyloin
P
P
P
C-C
- H +
Scheme 2.193 Thiamine diphosphate-dependent carboligation of aldehydes (acyloin reaction)
218
2 Biocatalytic Applications