Chemistry Reference
In-Depth Information
parable reactivity. The formation of an aldimine Schiff base of
36
with the substrate
-
amino acid was not the rate-determining step. Conversely, indole derivatives showed
marked substrate specificity; relative reactivities for the reactions of
L-
serine with 5-
hydroxyindole, 5-methylindole, 5-methoxyindole, and indole were 40, 18, 13, and 1,
respectively. Such selectivity for indole derivatives primarily reflects differences in
their nucleophilicity.
Modest enantioselectivity was observed for the
a
-replacement reaction catalyzed by
33
-
36
bilayer membranes [45].
D-
Tryptophan formation prevailed over that of the
L-
form in 50-55% ee regardless of chirality of the substrate, serine. Conversely, no en-
antioselectivity was observed when the
32
vesicle was used in place of
33
. This sug-
gested that the imidazolyl group of
33
might exercise stereospecific acid catalysis in the
protonation of the prochiral carboanion intermediate. The enantioselectivity was also
modest (ca. 30% ee) when the
b
-replacement reaction was mediated by the co-vesicle
formed with
37
,
32
, and an additional peptide lipid having (S)-binaphthol moieties (
35
)
in the presence of Cu(
II
) ions.
b
2.6
Aldolase-type Reactions
Serine hydroxymethyltransferase is a PLP-dependent aldolase. It catalyzes interconver-
sion between glycine and various
-amino acids, such as serine and threo-
nine, via formation of a quinoid intermediate derived from PLP with the amino acid
substrate (Scheme 2.9). This aldolase-type reaction is of interest as an asymmetric
synthesis of
b
-hydroxy-
a
-amino acids via C-C bond formation.
Kuzuhara et al. synthesized an optically resolved pyridoxal analog having an “ansa
chain“ between the 2
0
- and 5
0
-positions (
45
) [46]. The aldolase-type reaction of
45
and
glycine with either acetaldehyde or propionaldehyde afforded the corresponding
a
b
-hy-
a
droxy-
-amino acid with 27-77% ee. The erythro isomers were 1.2-1.8 times domi-
nant over threo ones. The (S)-enantiomer of the pyridoxal derivative furnished the (S)-
amino acid in excess. Accordingly, the reaction occurred on the same face as was oc-
cupied by the ansa chain. We have confirmed these results [47].
We also prepared a chiral cyclophane derivative of pyridoxal (
46
) that has amino
groups oriented specifically over one face of the cofactor [47]. The (S)-isomer of
this compound mediated the formation of threonine and allo-threonine from glycine
and acetaldehyde with enantioselectivities that were a function of pH, reversing the
chiral selectivity from low to high pH. Explanations were advanced for this stereoche-
mical reversal and for the otherwise surprising preference of the former compounds to
react on the more hindered face of the pyridoxal. We suggested that the reaction inter-
mediate was geometrically distorted by the transannular chain, leading to reaction on
the face that carried the chain due to a stereoelectronic effect (Figure 2.7). The stereo-
chemical reversal seen with
46
, as controlled by pH, may reflect catalysis by the pro-
tonated form (Figure 2.8), but a coordination effect of metal ions bound to the pro-
tonation-free form cannot be excluded. We also recently observed a similar stereoche-
mical reversal with catalyst
42
[42].
