4th EucheMs chemistry congress

Poster Session 1
s1004
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
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reSoLution of tert-ButyL-3-hydroxy-4-
-PhenyLPyrroLidine-1-CArBoxyLAte
d. BALoGh 1 , e. KovACS 1 , f. fAiGL 1
1 Budapest University of Technology and Economics,
Department of Organic Chemistry and Technology, Budapest,
Hungary
In kinetic resolution two enantiomers react with different
rates in a chemical reaction. If there is a large difference between
the two reaction rate constants, practically only one of the isomers
takes part in the reaction, the other one stays unreacted. Kinetic
resolution can be carried out in the presence of chiral catalysts.
Enzymes, such as hydrolases are highly suitable for this purpose. [1]
Our goal was to prepare a racemic pyrrolidine derivative and
work out its enzymatic resolution. It can be an intermediate of the
synthesis of chiral ligands and could be useful for the
pharmaceutical industry. Many compounds with the similar
structure were proved to have biological effects such as
iminosugars, which are potential inhibitors of glucosidase
enzymes [2] or kainic acid derivatives that have a potent central
nervous system stimulant activity [3] .
In the course of our research, we synthesized trans
tert-butyl-3-hydroxy-4-phenylpyrrolidine-1-carboxylate from
tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate in a
Grignard-reaction. Kinetic resolution of the racemic secondary
alcohol was investigated using enzyme catalysed acylation. Series
of experiments were accomplished in order to find the most
efficient enzyme, solvent and temperature, thus we could prepare
the optically active (3R,4S)-alcohol isomer with high enantiomeric
purity.
The optically active ester was separated from the
(3R,4S)-alcohol by flash chromatography. Alcoholysis of the ester
was performed in different alcohols catalysed by Novozym 435
enzyme, which proved to be the most efficient in the previous
experiments. With this method also the (3S,4R)-isomer of the
alcohol can be prepared in high enantiomeric excess.
references:
1. Yamada H., Shimizu S., in: Biocatalysts in Organic
Synthesis, Tramper, H. C., Plas. P., Linko P. (Eds.),
Amsterdam: Elsevier, 1985; pp 19-37
2. U.S. 3691198 patent (1972)
3. P. Gill, W.D. Lubell: J. Org. Chem., 60, 2658 (1996)
Keywords: Enzymes; Kinetic resolution; Acylation;
Enantioselectivity; Heterocycles;
4 th EucheMs chemistry congress
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GrowinG PoLy(diSuLfide) CeLL-PenetrAtinG
PePtideS on thioLAted CArGo
e. K. BAnG 1 , S. MAtiLe 1
1 University of Geneva, Department of Organic Chemistry,
Geneva, Switzerland
The activities of dynamic polyion-counterion complexes in
lipid bilayer membranes have been studied for their scientific
utilities as transmembrane transporters / carriers, voltage gates,
and sensors. Our dynamic amphiphiles, having dynamic bonds
between their charged head and their hydrophobic tails, can
activate biomolecules (DNAs, siRNAs, CPPs) as counterion
transporters. [1] We currently are expanding this concept to
poly(disulfide)s, dynamic polymers with disulfide repeats in their
main chain, to deliver biomolecules through the cellular
membrane. [2] The disulfide bond is a dynamic covalent bond,
which can be easily cleaved and reformed, but stronger than the
non-covalent interactions present in supramolecular polymers.
Moreover, it is degradable via reductive depolymerization by
glutathione in cells. The general objective of this project is to let
poly(disulfide) CPPs grow directly on thiolated initiators of free
choice (siRNA, drugs, probes) before their cellular uptake, and
have them removed afterwards in the cytosol. Here, we report the
synthesis of guanidinium-containing disulfide propagators and
their polymerization by thiol-initiated ring-opening disulfide
exchange. [3] The polymerization and depolymerization processes
were monitored by measuring transport activity in fluorogenic
vesicles, and by size exclusion chromatography, light scattering
and mass spectrometry, including fluorescent initiators and
terminators for FRET-analysis. We hope that the resulting method
will provide general access to non-toxic delivery in native form.
references:
1. a) T. Takeuchi, J. Montenegro, A. Hennig, S. Matile,
Chem. Sci. 2011, 2, 303-307;
b) J. Montenegro, E.-K. Bang, N. Sakai, S. Matile,
Chem. Eur. J., in press (EuCheMS Issue).
2. a) J. Montenegro, C. Gehin, E.-K. Bang, A. Fin,
D. Alonso Doval, H. Riezman, S. Matile, Chimia 2011,
65, 853-858;
b) E.-K. Bang, M. Lista, G. Sforazzini, N. Sakai, S. Matile,
Chem. Sci., 2012, DOI:10.1039/C2SC20098H.
3. N. Sakai, M. Lista, O. Kel, S. Sakurai, D. Emery, J. Mareda,
E. Vauthey, S. Matile, J. Am. Chem. Soc. 2011, 133,
15224-15227.
Keywords: Peptides; Polymers; Ring-opening polymerization;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc