4th EucheMs chemistry congress

wednesday, 29-Aug 2012
s716
chem. Listy 106, s587–s1425 (2012)
life sciences
Medicinal Chemistry session – ii
o - 3 2 5
C-2 funCtionALizAtion of PiPeridineS viA
direCted trAnSition MetAL-CAtALyzed SP3 Ch
ACtivAtion
B. MAeS 1
1 University of Antwerp, Chemistry, Antwerp, Belgium
The development of transition metal-catalyzed methods for
the direct functionalization of sp3 C-H bonds is one of the current
challenges in organic chemistry. [1] Within this area, the
transformation of a C-H bond in alpha-position to the nitrogen
atom of saturated cyclic amines is of great importance [2] since
such heterocyclic motifs can be found in an impressive number
of natural products and marketed drugs. To date, examples of
direct C2-H functionalization of cyclic amines using transition
metal-catalysis are still rare. The direct functionalization studies
published thus far have mainly focused on pyrrolidines and only
show (if any) a limited number of piperidine examples.
We have developed a direct Ru-catalyzed C-2 arylation and
alkylation protocol which can be used on unsubstituted and
substituted piperidines. The arylation protocol employs
arylboronate esters and the alkylation alkenes as reagents. [3, 4]
The procedures require a directing group on the piperidine
nitrogen. We used a pyridine directing group which has always
been considered as a non removable group and developed
protocols to remove it in a straightforward manner.
references:
1. a) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.;
Baudoin, O. Chem. Eur. J. 2010, 16, 2654.
b) Baudoin, O. Chem. Soc. Rev., 2011, 40, 4902.
2. Campos, K. R. Chem. Soc. Rev. 2007, 36, 1069.
3. Prokopcová, H.; Bergman, S.D.; Aelvoet, K.; Smout, V.;
Herrebout, W.; Van der Veken, B.; Meerpoel, L.;
Maes, Bert U.W. Chem. Eur. J. 2010, 16, 13063.
4. Bergman, S.D.; Thomas, E.S.; Aelvoet, K.; Diels, G.;
Meerpoel, L.; Maes, Bert U.W. Chem. Eur. J. 2012, 18,
in press.
Keywords: C-H activation; Homogeneous catalysis;
Ruthenium;
Medicinal Chemistry session – ii
4 th EucheMs chemistry congress
o - 3 2 6
deveLoPMent And APPLiCAtion of reverSiBLe
enriChMent tAGS for nAturAL ProduCt
diSCovery
d. trAder 1 , A. SideBottoM 1 , e. CArLSon 1
1 Indiana University, Chemistry, Bloomington, USA
Although natural product isolation can be a laborious task,
it has yielded myriad drug candidates and inspired synthetic
chemists for over a century. Considerable advances have been
made in separation technology; however, additional methods are
needed to streamline drug discovery efforts. Purification of the
active components of a crude extract, which often represent less
than 1% by weight, is considered a major bottleneck in natural
products discovery. Current isolation techniques are dependent
upon the physicochemical properties of the molecules such as
polarity or charge. These strategies often provide mixed
fractions upon purification, increasing the difficulty of bioassay
assessment or structural determination of unknown molecules.
To address these issues, we have developed a new method to
isolate natural products based upon an orthogonal property, their
functional group composition. This technique utilizes reversible
enrichment tagging reagents, which react chemoselectively with
the desired functional group class faciliting enrichment from
complex mixtures. Our previous studies yielded the
development of a functional group-specific method for
enrichment of hydroxyl group-containing natural products based
upon the formation of a silyl ether bond. We were then able to
extend our developed silicon chemistry to yield a novel
diisopropylsiloxane-functionalized resin that chemoselectively
captures natural products containing a carboxylic acid moiety.
With these two enrichment tags in hand our goal is to isolate
previously undiscovered molecules from well-characterized
strains of Streptomyces. Additionally, work on a third and fourth
enrichment tag, one that is chemoselective for the aldehyde or
ketone functionality and the phenol, is also under way.
Keywords: natural products; Immobilization; Solid-phase
synthesis; Antibiotics;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc