4th EucheMs chemistry congress

Poster Session 2
s1342
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
P - 0 9 5 9
PrePArAtion of 3-thiourenido-2-indoLoneS
And 2-thioxoiMidAzo[4,5-C]quinoLin-4-oneS
froM 3-hydroxyquinoLine-2,4-dioneS
o. rudoLf 1 , A. LyCKA 2 , z. CernoCh 1 , A. KLASeK 1
1 Tomas Bata University in Zlin Faculty of Technology,
Department of Chemistry, Zlin, Czech Republic
2 Research Institute for Organic Syntheses (VUOS), Research
Institute for Organic Syntheses (VUOS), Rybitvi Pardubice,
Czech Republic
3-Aminoquinoline-2,4-diones, accessible by amination of
3-chloroquinoline-2,4-diones, [1] reacts with in situ generated
isothiocyanic acid to give mainly 3-thiourenido-2-indolones.
3-Benzyl derivatives of 3-aminoquinoline-2,4-diones yield
2-thioxoimidazo[4,5-c]quinolin-4-ones. [2, 3]
These interesting results gave us incentive to perform
analogous reactions with 3-hydroxyquinoline-2,4-diones, which
are obtainable by oxidation of 4-hydroxyquinoline-2-ones. [4]
Our intention was to prepare oxa-analogues of
thioxoimidazoquinolinones and thiourenidoindolones. However,
no reaction was observed when a model compound
1-methyl-3-hydroxy-3-phenylquinoline-2,4-dione was boiled with
potassium thiocyanate.
On the other hand, 3-(3'-benzoylthioureido)-1-methyl-2-
-oxo-2,3-dihydro-1H-indole was isolated when KSCN was
substituted by NH SCN. The same results were obtained with
4
another 3-hydroxyquinolinediones (R and R = Me, Bu, Ph). In
1 2
addition, using starting compound 3-hydroxyquinolinediones
bearing a benzyl group in position 3, C-debenzylation under
formation of thioxoimidazoquinolinones was observed.
The exhaustive results will be discussed and the reaction
mechanism will be proposed.
Acknowledgement: This study was supported by the internal
grant of TBU in Zlín No. IGA//FT/2012/015 funded from the
resources of specific university research.
references:
1. Kafka S. et al., Heterocycles, 2002, 57, 1659;
2. Mrkvicka et al., Tetrahedron, 2010, 66, 8441;
3. Mrkvicka et al., Tetrahedron, 2011, 67, 2407;
4. Kafka S. et al., J. Heterocyclic Chem., 1996, 33, 1977.
Keywords: quinoline-2,4-diones; isothiocyanic acid;
3-aminoquinoline-2,4-diones; 3-hydroxyquinoline-2,4-diones;
C-debenzylation;
4 th EucheMs chemistry congress
P - 0 9 6 0
ProduCtivity enhAnCeMent of C=C
BioreduCtionS By CouPLinG the in Situ
SuBStrAte feedinG ProduCt reMovAL
teChnoLoGy with iSoLAted enzyMeS
A. SACChetti 1 , G. frAnCeSCo G. 1 , B. eLiSABettA 1 ,
P. fABio 1 , M. dAnieLA 2
1 Polytechinc of Milan, Department of Chemistry “G. Natta”,
Milano, Italy
2 CNR, Institute of Chemistry ICRM, Milano, Italy
The bioreduction of C=C double bond of prochiral
aldehydes is an important synthetic tool for the generation of
optically pure synthones. The first examples of such a reaction
were carried out using resting cells of Saccharomyces cerevisiae. [1]
In the last decade, great improvement, in terms of conversion and
simplicity of work-up, has been achieved using isolated enoate
reductases (ERs), such as the Old Yellow Enzymes (OYEs),
instead of the whole microorganism. However, the productivity
of these reactions is generally low, mainly due to the low substrate
concentration used in most experimental set-ups. In addition, the
products of isolated ERs-catalyzed reactions are saturated
aldehydes which are intrinsically unstable compounds. [2] Here
we describe the combination of multienzymatic systems,
comprising selected OYEs and alcohol dehydrogenases (ADHs),
with the SFPR (in situ Substrate Feeding Product Removal)
concept. When applied to the reduction of a set of different
prochiral α,β-unsaturated aldehydes to the corresponding
saturated products (e.g. some important synthons for the
preparation of the bioactive molecules Robalzotan and
Rotigotine), this strategy allows an average
100-fold improvement of productivity and helps to preserve the
optical purity of products and the chemical stability of reagents.
We also observed a remarkable chemoselectivity of selected
ADHs toward saturated aldehydes in the presence of α,βunsaturated
aldehydes. [3]
references:
1. a) S. Servi, Synthesis 1990, 1;
b) R. Csuk, B.I. Glänzer, Chem. Rev. 1991, 91, 49.
2. C. Stueckler, N.J. Mueller, C.K.Winkler, S.M. Glueck,
K. Gruber, G. Steinkeller, K. Faber Dalton Trans. 2010,
39, 8472.
3. a) M. Bechtold, E. Brenna, C. Femmer, F.G. Gatti,
S. Panke, F. Parmeggiani, A. Sacchetti, Org. Process
Res. Dev. 2012, 269
b) E. Brenna, F.G. Gatti, D. Monti, F. Parmeggiani,
A. Sacchetti, Chem. Comm. 2012, 79
Keywords: Biocatalysis; Reduction;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc