Chemistry Reference
In-Depth Information
catalyzed, with a rate 150-fold higher than that for a thiazolium salt lacking the cyclo-
dextrin. Interestingly, in this benzoin condensation the rate-determining step - addi-
tion of anion
8
to the second benzaldehyde - allowed the benzaldehyde units to bind
next to each other in the cavity, but in the product benzoin
9
the extended geometry
does not permit this. Thus the benzoin product did not bind strongly to the artificial
enzyme
6
, and did not inhibit the process. Our other studies on the benzoin condensa-
tion [65, 66] revealed geometries of the transition state and product that support this
interpretation.
1.2
Mimics of Enzymes that use Pyridoxamine and Pyridoxal Phosphates as Coenzymes
We also attached pyridoxamine to a cyclodextrin and saw that the resulting enzyme
mimics showed good substrate selectivity in the conversion of keto acids into amino
acids [67-71]. With a pyridoxamine doubly-linked to the cyclodextrin there was a pre-
ference for the hydrophobic t-butylphenylpyruvic acid relative to pyruvic acid of at least
15 000-fold. We also made a related system, in which a synthetic macrocycle was at-
tached to the coenzyme mimic [72], that also showed substrate selectivity. In other
work we synthesized molecules in which base groups attached to the pyridoxamine
could perform transaminations with good stereoselectivity [73-75]. We also made
others in which the geometry of the attached base groups could promote different
catalyzed processes for pyridoxal, selecting among the various enzymatic processes
for which pyridoxal phosphate is a coenzyme [76-80].
These and subsequent artificial enzymes that perform transaminations are de-
scribed in Chapter 2.
1.3
Artificial Hydrolytic Enzymes
1.3.1
Chymotrypsin Mimics
The field of artificial enzymes has been greatly concerned with mimicking hydrolytic
enzymes. Since the enzyme chymotrypsin was one of the first to be extensively studied
and understood, many laboratories have created artificial peptidases and esterases,
including those that use the nucleophilic mechanism like that in chymotrypsin. (How-
ever, one chymotrypsin mimic from other laboratories did not have the reported me-
chanism [81].) The critical requirement is bifunctional catalysis, which in chymotryp-
sin involves imidazole acting first as a general base, then as a general acid, and the
serine hydroxyl group serving as a nucleophile. I have pointed out the special kinetic
situation this mechanism implies [82].
