4th EucheMs chemistry congress

Monday, 27-Aug 2012
s703
chem. Listy 106, s587–s1425 (2012)
life sciences
Biocatalysis session – i
o - 0 5 0
in SiLiCo diSCovery And APPLiCAtion of
trAnSAMinASeS in orGAniC SyntheSiS
C. viCKerS 1 , M. hohne 1 , u. BornSCheuer 1
1 Institute of Biochemistry, Dept. of Biotechnology & Enzyme
Catalysis, Greifswald, Germany
Transaminases are versatile enzymes for the synthesis of
optically pure amines. [1] We have developed a protecting group
strategy to broaden the substrate range, enhance reaction rates and
enantioselectivity in w-transaminase-catalyzed kinetic resolutions. [2]
To enable an efficient asymmetric synthesis to obtain the desired
amine in high yield, the w-transaminase-catalyzed reaction was
coupled with pyruvate decarboxylase. [3] This led to a
considerable shift in the reaction equilibrium by formation of
carbon dioxide and acetaldehyde. Furthermore, two
high-throughput methods for the rapid determination of
conversion and amino donor/acceptor spectrum were developed. [4, 5]
Finally, a detailed in silico analysis algorithm was designed. This
enabled the discovery of a toolbox of 17 (R)-selective
transaminases [6] from >5,000 protein sequences of enzymes from
the PLP-superfamily with predicted substrate type and
enantiopreference. These new transaminases showed excellent
activity and strict (R)-selectivity in the asymmetric synthesis of a
broad set of chiral amines. [7]
references:
1. Höhne, M., Bornscheuer, U.T. ChemCatChem, 2009, 1, 42.
2. Höhne, M., Kühl, S., Robins, K., Bornscheuer, U.T.
ChemBioChem, 2007, 9, 363.
3. Höhne, M., Robins, K., Bornscheuer, U.T. Adv. Synth.
Catal., 2008, 350, 807.
4. Schätzle, S., Höhne, M., Robins, K., Bornscheuer U.T.
Anal. Chem., 2010, 82, 2082.
5. Schätzle, S., Höhne, M., Redestad, E., Robins, K.,
Bornscheuer U.T. Anal. Chem., 2009, 81, 8244.
6. Höhne, M., Schätzle, S., Jochens, H., Robins, K.,
Bornscheuer, U.T. Nature Chem. Biol., 2010, 6, 807.
7. Schätzle, S., Steffen-Munsberg, F., Thontowi, A., Höhne,
M., Robins, K., Bornscheuer, U.T. Adv. Synth. Catal.,
2011, 353, 2439.
Keywords: Biocatalysis; Enantioselectivity; Asymmetric
synthesis;
Biocatalysis session – i
4 th EucheMs chemistry congress
o - 0 5 1
SynthetiC StudieS towArdS dihyPoeStoxide
M. urooS 1 , C. J. hAyeS 1
1 The University of Nottingham, School of Chemistry,
Nottingham, United Kingdom
The synthetic studies have been described towards
diterpene derived complex natural product dihypoestoxide via a
hetero-Diels-Alder dimerisation of its proposed biosynthetic
precursor, hypoestoxide. The tricyclic spirochroman core of
dihypoestoxide has been synthesised from geranoic acid in seven
steps using a hetero-Diels-Alder cycloaddition as a key step, thus
providing support for the proposed biosynthesis of the natural
product. Furthermore, analysis of the 13C NMR data obtained
for all four diastereoisomers of the synthetic spirochroman core
has allowed us to propose a full stereochemical assignment
for dihypoestoxide. [1] Our synthetic strategy towards
hypoestoxide was based on a biomimetic approach by converting
epiverticillol into its more oxygenated variant, hypoestoxide,
A hetero-Diels-Alder dimerisation of hypoestoxide would then
result into dihypoestoxide.
references:
1. Uroos, M.; Hayes, C. J. Org. Lett. 2010, 12, 5294.
Keywords: Synthesis design; Synthetic methods; Natural
products; biomimetic synthesis; biosynthesis;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc