Biomedical Engineering Reference
In-Depth Information
5.5.3.4 The Use of Chiral Reagents and Catalysts
The main disadvantage of using a chiral auxiliary is that additional steps are required in the syn-
thesis for appendage and removal of the chiral group. One method of overcoming this is to use
a chiral catalyst to promote the conversion of an achiral starting material into a chiral product.
By dei nition, the advantage is that only a small molar ratio of catalyst is required, which can be
recovered and reused. One of the most widely exploited areas of catalytic asymmetric synthesis
is hydrogenation using a chiral transition metal complex. Two important ligands in this area are
BINAP and DIPAMP (Figure 5.14), which are often complexed to rhodium (II) or ruthenium (II)
acetate. DIPAMP is used in the industrial synthesis of (
S
)-3,4-dihydroxyphenylalanine (l-DOPA),
an anti-Parkinson's agent.
OMe
Ph
2
O
O
OMe
P
Rh
Ph
O
P
P
P
O
Ph
2
Ph
(
S
)-BINAP-Rh(OAc)
2
(
R
,
R
)-DIPAMP
FIGURE 5.14
Two commonly utilized chiral catalysts for performing asymmetric hydrogenations. BINAP
(right) is shown as its octahedral rhodium acetate complex.
5.5.3.5 The Use of Enzymes and Whole Organisms
Enzymes are nature's chiral catalysts, which are extremely versatile in catalyzing almost every
known chemical reaction. It is now generally agreed that enzymes can accommodate a variety of
structurally diverse substrates and some can be used under a wide variety of conditions, this being
particularly applicable to the extremophile class of enzyme which can be isolated from microbes
capable of surviving in extreme environments.
Enzymes catalyzing a wide variety of chemical reactions are available for enantioselective syn-
thesis (Table 5.1) and thanks to the advent of molecular biological techniques the choice of enzyme is
not restricted to those found in nature. High-throughput screening methods can be used to discover
TABLE 5.1
The Classifi cation of Enzymes
Enzyme Class
Examples of Enzymes
Reactions Catalyzed
1. Oxidoreductase
Dehydrogenases, oxidases,
peroxidases
Oxidation/reduction reactions
2. Transferase
Aminotransferases
Group transfer reactions (e.g., methyl,
acyl, and phosphate)
3. Hydrolase
Lipases/esterases, proteases,
amidopeptidases, acylases,
hydantoinases
Hydrolysis (e.g., esters, amides, and
hydantoins)
4. Lyase
Decarboxylases, dehydratases,
aldolases, oxynitrilases
Additions to, or formation of, C=C, C=O,
or C=N bonds
5. Isomerase
Racemases, epimerases
Structural and geometric rearrangements
6. Ligase
DNA ligase
Formation of C−C, C−N, C−O, or
C−S bonds
