Table 1.4 lists some representative values of enantiomeric excess of product
(e.e.) corresponding to a given ΔΔG
6 ¼ of the reaction.
Due to the logarithmic dependence between ΔΔG
6 ¼ and e.e. of the product
(Fig. 1.8), even a very small difference in free energy (e.g., 0.65 kcal/mol) can
lead to a considerable enantiomeric excess of product (50%) (Table 1.4) and only a
modest 1.75 kcal/mol is required to reach ~90% e.e. However, the same amount of
ΔΔG
6 ¼ is roughly needed to push this value further to 99%! For virtually absolute
selectivities, however, ΔΔG
6 ¼ has to be considerably higher (!4.50 kcal/mol).
Hence, the influence of ΔΔG
6 ¼ on the stereoselectivity of the reaction is very
sensitive, which makes accurate predictions virtually impossible.
1.4.3 Classification and Nomenclature
At present about 6500 enzymes have been recognized by the International Union of
Biochemistry and Molecular Biology (IUBMB) [139–142] and if the prediction that
there are about 25,000 enzymes existing in Nature is true [143], the bulk of this vast
v B
v A
ΔΔG = - RT ln
ΔΔG = ΔΔH - T • ΔΔS
[EnzB]
Enz + Q
+ B
+ A
Enz + P
[EnzA]
Enz
ΔΔG
[EnzB]
[EnzA]
Reaction coordinate
Enz + Q
Enz + A or B
Enz + P
(slow)
(fast)
ΔG
≠
≠
≠
≠
≠
≠
≠
Fig. 1.8 Energy diagram for an enzyme-catalyzed enantioselective reaction. Enz enzyme, A and B
enantiomeric substrates, P and Q enantiomeric products; [EnzA] and [EnzB] diastereomeric enzymesubstrate complexes;
6
¼ denotes a transition state, ΔΔG, ΔΔH and ΔΔS free energy, enthalpy, and
entropy difference, resp., R gas constant, T temperature, v A and v B reaction velocities of A and B, resp.
Table 1.4
Free energy values ΔΔG
6 ¼ for representative optical purities of product (e.e.) and the
corresponding ratio of reaction rates of enantiomers (v A , v B )
ΔΔG
6 ¼ [kcal/mol]
v A /v B
e.e. [%]
0.118
1.2
10
0.651
3
50
1.74
19
90
2.17
39
95
3.14
199
99
4.50
1999
99.9
e:e: %
½ Š ¼
PÀQ
PþQ Â 100
20
1 Introduction and Background Information