Chemistry Reference
In-Depth Information
2.4
Decarboxylation
Decarboxylation of an amino acid is an important reaction, catalyzed by a pyridoxal-
dependent decarboxylase, that affords an amine as product (Scheme 2.6). It is very
attractive to learn how to mimic this process to generate various amines from
a
-amino
a
acids. Unfortunately, our previous studies established that treatment of
-alkyl amino
acids with pyridoxal afforded only ketone and pyridoxamine as products, by a transa-
mination-dependent oxidative decarboxylation process (pathway b in Scheme 2.5) [41].
Consequently, non-oxidative decarboxylation, using pyridoxals to generate amines, re-
mains elusive.
We also studied the pyridoxal-dependent decarboxylation of an aminomalonic acid, a
process providing an
-amino acid as the product. Our interest was to induce stereo-
selectivity in the process. Therefore, we synthesized catalysts
42
and
43
, which rigidly
held chirally mounted groups [42]. With the basic
42
we obtained 42% ee favoring
L-
phenylalanine in the decarboxylation of 2-amino-2-benzyl-malonic acid, while with
non-basic
43
the ee was too low to detect. We proposed that the basic side chain de-
livered a proton to the decarboxylation intermediate in a stereoselective fashion.
a
2.5
b
-Elimination and Replacement
b
-amino acid with a nucleophile is
very attractive from the viewpoint of synthetic organic chemistry because various
-Elimination and then replacement reaction of an
a
b
-
substituted alanines may be prepared from a simple
-amino acid, such as serine, and
nucleophiles. A reaction catalyzed by tryptophan synthase - the formation of trypto-
phan from serine and indole - is one of the most well-known
a
-elimination and re-
placement reactions (Scheme 2.7). Here, an aldimine Schiff base is derived from re-
action of the enzyme-bound PLP with serine, which then dehydrates to give the Schiff
base of PLP with 2-aminoacrylate. Indole then adds to the vinyl Schiff base, generating
tryptophan after lysine aminolysis of the Schiff base product.
We studied the
b
-elimination and replacement reactions using our pyridoxamine
analogs [43]. Initially, we examined the relative rates for the
b
-elimination reactions
between chloropyruvic acid and small pyridoxamine analogs carrying a basic side
chain (Table 2.2). In the dimethylamino series the HCl elimination rates were fastest
with the shorter chain of
4
, as expected for a process that requires only proton removal
from the pyridoxamine 4'-CH
2
group. The contrast with the data for transamination
b
