Project Details
Abstract
Enzyme-catalyzed kinetic resolution is to enantioselectively resolve the racemate such
that the resulting chiral product can be separately from remaining chiral substrate via
conventional unit operation processes. For the past years, this laboratory has employed
approaches of medium engineering, immobilized enzyme techniques, and substrate
engineering for developing lipase-catalyzed resolution processes. However, there still
exists a bottleneck that the rate-determining step will change and leads to reduced
enantioselectivity, when employing conventional racemic acids, alcohols, amines, estes,
amides and thioesters as the substrates. However recently, we have found that by
combining the azoles chemistry with lipase resolution ability on using (R,S)-N-acylazoles
(i.e. (R,S)-N-azolides) as the substrate, the bottleneck can be overcome, and thus induce
our motivation to submit the research proposal.
In the following three years, we will focus on developing the lipase-catalyzed
resolution platform for preparing chiral carboxylic acids, alcohols and amines. In the first
year, the combinatorial resolution for (R,S)-N-azolides containing an α-chiral center is
studied, in which effects of the acyl and leaving alcohol azole containing substituents on
the enzyme performance will be investigated and compared with those using simple azoles
without containing the substituent. Moreover, the kinetic analysis will be carried out to
elucidate the optimal enantioselectivity when varying the leaving azole moiety. In the
second year, (R,S)-azole-N-carboxylates are first synthesized from (R,S)-alcohols and then
employ for performing the lipase-catalyzed hydrolytic resolution. This approach is different
from the conventional resolution of using (R,S)-alcohol as an acyl acceptor, i.e. the (R)-
and (S)-alcohol of (R,S)-azole-N-carboxylate as an acyl donor allocating in the acyl pocket
of the catalytic active site. In the third year, the research will be extended to the resolution
(R,S)-amines. However, new derivatives of (R,S)-N-oxalamic azoles from (R,S)-amines,
oxayl dichloride and azole will be synthesized, and then are employed as the substrate for
lipase-catalyzed hydrolysis. It stresses that this approach is also different from the
conventional resolution of using (R,S)-amine as an acyl acceptor, i.e. the (R)- and
(S)-amine of (R,S)-N-oxalamic azoles as an acyl donor allocating in the acyl pocket of the
catalytic active site (details are described in the following section).
Project IDs
Project ID:PB9907-12643
External Project ID:NSC99-2221-E182-028
External Project ID:NSC99-2221-E182-028
Status | Finished |
---|---|
Effective start/end date | 01/08/10 → 31/07/11 |
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.