4th EucheMs chemistry congress

Poster Session 2
s1299
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
P - 0 8 7 2
A hiGhLy ConverGent route towArdS
4-AMino-4-deoxy-L-ArABinoSe Modified LiPid A
r. hoLLAuS 1 , P. KoSMA 1 , A. zAMyAtinA 1
1 University for Natural Resources and Applied Life Sciences,
Chemistry, Vienna, Austria
Lipid A of gram negative bacteria anchors the
lipopolysaccharide chain to the outer cell membrane. It possess a
rather conservered structure: To a β(1-6) diglucosamine backbone
are phosphates attached at positions 1 and 4'. Different acylation
pattern are possible for positions 2-N, 2'-N, 3, 3', were
(R)-3-hydroxy or (R)-3-acyloxy fatty acids could be attached.
Covalent modification of Lipid A by cationic β-L-Ara4N at
either both 1- and 4'- phosphates or solely at the reducing
phosphate, which is characteristic for Burkholderia strains, is
associated with augmented bacterial virulence, resistance to
antibiotic treatment and modulation of TLR4-MD-2-mediated
innate immune response. Mono- and bis- β-L-Ara4N substituted
Lipid A structures, corresponding to native Burkholderia Lipid A
were synthesised.
Starting from glucosamine, an orthogonally protected Glc2N
key intermediate was assembled, carrying 2-N-Troc-,
1-O-TBDMS- and 4,6-O-anisyliden protecting groups, position 3
was acylated with (R)-3-(((allyloxy)car-bonyl)oxy)tetradecanoic
acid. The compound was used for the synthesis of a glycosyl
donor by regioselective reductive opening of 4,6-O-anisylidene
acetal to furnisch 4-OPMB ether, followed by 6-O-Alloc
protection, 1-O-desilylation and subsequent appel reaction to give
a bromide donor. Glycosyl acceptor was prepared in a convergent
manner using the same precursor by acetal opening to provide
6-O-PMB ether, 4-O-Alloc protection, cleavage of 2N-Troc group
followed by acylation with 3-oxyacyl lipid chain. Subsequent
6-O-PMB deprotection and glycosylation of the liberated 6-OH
by bromide donor, reductive cleavage of 2'-N-Troc protection and
N-acylation afforded fully protected pentaacylated β(1-6)
diglucosamine disaccharide. Regioselective deprotection of
positions 4'-O-PMB and 1-O-TBMS allowed for selective
coupling with either diallyl-N,N-diisopropylphosphoramidite
or H-phosphonate of 2,3-di-O-Alloc-protected β-L-4-azido-
-arabinose, respectively, leading, after global deprotection (Alloc
deprotection followed by azide reduction), to target Burkholderia
Lipid A structures.
Keywords: Synthetic methods; Carbohydrates;
Phosphorylation; Phospholipids; Azides;
4 th EucheMs chemistry congress
P - 0 8 7 3
unuSuAL BehAviour of
5-(2-PyridyL)SuLfinyL-tetrAProPoxy -
CALix[4]Arene in Pd-CAtALyzed reACtion.
J. hoLuB 1 , v. eiGner 1 , P. LhotáK 1
1 Institute of Chemical Technology in Prague, Department of
Organic Chemistry, Prague 6, Czech Republic
Palladium catalyzed cross-coupling reactions using direct
C-H bond activation is very attractive topic in modern synthetic
organic chemistry. The presence of a directing group usually
enables regioselective introduction of the coupling agent into a
specific position. Among these groups, the 2-pyridylsulfinyl
moiety possesses very strong C-H activating properties. We have
introduced this directing group into the upper rim of calix[4]arene
and attempted the direct arylation of calixarene skeleton into the
meta position. This reaction should provide very interesting
inherently chiral systems which could be useful in the design of
novel chiral receptors. Surprisingly, we have found that the
isolated product is not the expected aryl-substituted calixarene,
but some unknown, meta substituted and inherently chiral
calix[4]arene derivative. The NMR spectra of this compound were
very complicated and did not lead to the structure elucidation. On
the other hand, the single-crystal X-ray crystallography gave us
the final solution. The activation of the neighbour C-H bond (next
to the 2-pyridylsulfinyl directing group) led to the unexpected
intramolecular bridging of two meta positions on the proximal
phenolic subunits via a direct C-C bond. This kind of reaction has
never been observed in calixarene chemistry. The application of
this phenomenon for the synthesis of inherently chiral calixarenebased
receptors is currently underway.
Keywords: Calix[4]arene;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc