Chemistry Reference
In-Depth Information
A further non-natural reaction catalyzed by enzymes is the Morita-Baylis-Hillman
reaction. The Reetz group reported that this reaction is catalyzed by carrier proteins
such as serum albumins or certain lipases [170]. In the presence of these enzymes, the
Morita-Baylis-Hillman reaction of cyclohexenone with 4-nitrobenzaldehyde gives the
corresponding Morita-Baylis-Hillman adduct with conversions of up to 35% and enan-
tioselectivities of up to 19% ee.
6.5. ENANTIOSELECTIVE REDUCTIONS
6.5.1. Overview
The enantioselective transformation of C=X double bonds (with X=O, N, C) into cor-
responding reduced CH-XH single bonds (with X=O, N, C) plays a major role in
asymmetric synthesis. Notably, a range of redox enzymes (namely dehydrogenases) are
available, which catalyze the reduction of C=O double bonds under the formation of
the corresponding alcohol moieties. The reaction range comprises reduction of, for
example, ketones, α - and β - keto esters, and α-keto acids. Furthermore, reductive amina-
tion of C=O double bonds (of α-keto acids) using amino acid dehydrogenases turned
out to represent a highly effi cient approach toward the synthesis of enantiomerically
pure amino acids. A further class of redox enzymes (oxidoreductases) of common inter-
est in organic synthesis are enoate reductases. These enzymes catalyze the reduction of
activated C=C double bonds bearing at least one electron-withdrawing group as substitu-
ent. Although not belonging to the group of redox enzymes, transaminases also catalyze
“ reductive processes ” with both α-keto acids and ketones, thus leading to corresponding
amines and amino acids in an asymmetric fashion. In the following, such types of organic
synthetic reactions using oxidoreductases and transaminases will be discussed.
6.5.2. Reduction of Ketones
The asymmetric reduction of ketones represents a straightforward and an atom-econom-
ical approach toward the synthesis of optically active alcohols, and numerous effi cient
catalytic routes thereof have been developed up to date. Outstanding chemocatalytic
technologies are metal-catalyzed asymmetric hydrogenation of ketones [171] and borane
reduction [172], which are applied on technical scale and represent landmarks in indus-
trial asymmetric catalysis. In addition, biocatalytic reduction [173] turned out to be a
highly effi cient alternative and competitive technology for asymmetric ketone reduction.
This is underlined by an increasing number of industrial applications of biocatalytic
asymmetric reductions of ketones.
The principle of enantioselective biocatalytic reduction of ketones
116
is based
on the use of an alcohol dehydrogenase (ADH) as a catalyst, and a cofactor as a
reducing agent. An ADH is an enzyme capable of reducing carbonyl moieties under
formation of (chiral) alcohols (
R
) - or (
S
) -
117
and requires a specifi c “ cofactor ” as
reducing agent. The most preferred cofactors are either NADH or NADPH. Since the
cofactors are expensive reducing agents, and too costly to be applied in stoichiometric
amount, a common key feature of all preparative (and technical) biocatalytic reductions
is the use of cofactors in catalytic amount and their recycling
in situ
by coupling the
ketone reduction process with a second process, in which the cofactor is regenerated
(Scheme 6.46 ).
