4th EucheMs chemistry congress

Poster Session 2
s1343
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
P - 0 9 6 1
tetrAhydro-SS-CArBoLine-BASed
SPiroCyCLiC LACtAM AS PotentiAL tyPe ii'
SS-turn SoMAtoStAtine MiMetiC
A. SACChetti 1 , A. SiLvAni 2 , G. LeSMA 2 ,
M. MuSoLino 2 , r. CeCChi 3
1 Polytechinc of Milan, Chemistry, Milano, Italy
2 University of Milan, Chemistry, Milano, Italy
3 Sanofi-Aventis, Chemistry, Milano, Italy
The development of privileged molecular scaffolds
efficiently mimicking reverse turn motifs has attracted remarkable
interest when structural constraints are exploited to increase both
binding and selectivity of model peptides. One of the successful
approaches to restrict peptide conformation is the disubstitution
in the a position of an a-amino acid, leading to a conformational
constraint and a stereochemically stable quaternary carbon center.
In particular, spirocyclic scaffolds are able to provide, upon the
attachment of appropriate functional groups, useful high-affinity
ligands, relevant to the field of drug discovery. [1]
At present, we are interested to spirocyclic tryptophan (Trp)
analogues, in order to develop new reverse turn nucleating
moieties able to be inserted into pharmacologically relevant
peptidomimetic compounds. Among peptides sharing a
tryptophan-containing β-turn motif of which the Trp residue is
critical for binding, we looked at the hormone peptide
somatostatin, [2] acting in various organ systems as a
neuromodulator and a neurotransmitter, as well as a potent
inhibitor of various secretory processes and cell proliferation. [3]
Somatostatin and its analogue octreotide (Sandostatin ® drug,
clinically used for the treatment of endocrine tumors and
acromegaly) are thought to interact with the sst1-5 receptors
mainly by inserting a β-turn substructure, carrying a lysine (Lys)
and a Trp side chain into a pocket of the G protein-coupled
somatostatin receptor.
We report here the preparation and structural
characterization of a new 1,2,3,4-tetrahydro-β-carboline
(THBC)-based spirocyclic lactam as type-II' β-turn model
compound and the application of its core structure to the synthesis
of a somatostatin mimetic, whose biological evaluation is under
way.
references:
1. Van Rompaey, K. et al. D. Eur. J. Org. Chem. 2006,
2899–2911.
2. Janecka, A. et al. J. Pept.Res. 2001, 58, 91–107.
3. Reubi, G. C. Endocrine Reviews 2003, 24, 389–427.
Keywords: Conformation analysis; Peptidomimetics; Drug
design;
4 th EucheMs chemistry congress
P - 0 9 6 2
Sweet tASte inveStiGAtionS on ASPArtAMe
And neotAMe uSinG nMr SPeCtroSCoPy And
CoMPutAtionAL MethodS
B. SAGLAM 1, 2 , n. tuzun 1 , S. BeKiroGLu 2 , G. oruC 2, 3
1 Istanbul Technical University, Department of Chemistry, 34469,
Istanbul, Turkey
2 TUBITAK Marmara Research Centre, Food Institute, 41470
Gebze-Kocaeli, Turkey
3 Bogazici University, Department of Chemistry, 34342, Istanbul,
Turkey
Email: saglambi@itu.edu.tr
Aspartame (N-(L-α-Aspartyl)-L-phenylalanine,1-methyl ester)
is used as an artificial, non-saccharide sweetener in the
pharmaceutical and food industry and it is a dipeptide of aspartic acid
and phenylalanine. [1] Neotame ((3S)-3-(3,3-Dimethylbutylamino)-
-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic
acid) is a nonnutritive sweetener which is a derivative of
aspartame. It is a high-potency sweetener which is
6000–10 000 times sweeter than sucrose and 30-60 times sweeter
than aspartame. [2]
The aim of this research is to determine the relationship
between structure and taste for aspartame and neotame by using
NMR spectroscopy. Assignment of molecules are done by using
1D 1H and 13C, 2D homonuclear NOESY, TOCSY, and 2D
heteronuclear HSQC NMR spectra. Molecular interactions of
aspartame and neotame within cyclodextrin complexes are
investigated and findings are compared with the results that are
acquired from computational methods. Although aspartame and
neotame have similar structures, they have different taste quality.
3,3-dimethylbutyl group of neotame is the most efficient
substituent that makes the difference in taste. 2
references:
1. Sohajda T., Beni S., Varga E., Ivanyi R., Racz A., Szente L.,
Noszal B., Characterization of aspartame–cyclodextrin
complexation, Journal of Pharmaceutical and Biomedical
Analysis, Vol. 50, 2009, 737–745.
2. Nofre C., Tinti J. M., Neotame: discovery, properties,
utility, Food Chemistry, Vol. 69, 2000, 245-257.
Keywords: Nmr Spectroscopy; Cyclodextrin complexes;
Computational methods; Aspartame; Neotame;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc