ISMSC 2007 - Università degli Studi di Pavia

PSA 55
Molecular Recognition of Carbohydrates: New Synthetic Tripodal Receptors
Featuring Pyrrolic Binding Groups.
Cristina Nativi, a,b Martina Cacciarini, a Oscar Francesconi, a Alberto Vacca, c Gloriano Moneti, d
Andrea Ienco, e and Stefano Roelens. f
a Dipartimento di Chimica Organica, b Centro Risonanze Magnetiche (CERM), c Dipartimento di
Chimica, d Centro Interdipartimentale di Spettrometria di Massa (CISM), Universita` di Firenze,
e Istituto di Chimica dei Composti OrganoMetallici (ICCOM), f Istituto di Metodologie Chimiche
(IMC), Consiglio Nazionale delle Ricerche (CNR), Polo Scientifico e Tecnologico, I-50019 Sesto
Fiorentino, Firenze, Italy.
Carbohydrates are involved in many key processes in biological systems, like metabolism and
transport, cell-to-cell adhesion, immune response, cell infection by pathogens and enzyme
regulation. [1] All these processes are based on molecular recognition of carbohydrates, mainly
exploiting H-bonding interactions. To understand the chemical basis of these phenomena,
synthetic receptors mimicking the interaction between natural receptors and carbohydrates
were widely employed. [2] However, the design of effective receptors for selective recognition of
carbohydrates is yet an open challenge, for the achievement of which the comprehension of
structural and functional requirements for recognition is a crucial issue. Among the multitude of
artificial receptors reported in the chemical literature, benzene based tripodal structures have
been often employed giving interesting results. Effective recognition requires the establishment
of multiple binding interactions. In order to achieve the formation of an array of H bonds
between the host and the saccharidic guest, we have designed a receptor architecture that
O
HO
HO
OH OR
OH
HN
OH
NH
HN
NH
O HN
H
N
HN
H
N
HN
HO
HO HNOH
NH HN
OR
combines both aminic and pyrrolic functional groups into an acyclic tripodal benzene-based
scaffold. Indeed, aminic groups have been shown to be coordinatively complementary to
hydroxyl groups, [3] while pyrroles are well-established H-bonding donors. [4] Their combination
into a carefully designed architecture is thus believed to be effective for the recognition of
carbohydrates. In this communication we wish to describe the synthesis and the binding
properties of newly designed tripodal receptors, showing affinities for biologically relevant
monosaccharides among the largest reported in literature for neutral synthetic H-bonding
receptors.
[1]
B. Ernst, W. Hart, P. Sinay, Carbohydrates in Chemistry and Biology; Wiley-VCH: Weinheim,
Germany, 2000.
[2] A. P. Davis, T.
D. James, In Functional Synthetic Receptors; T. Schrader, , A. Hamilton, D.,
Eds.; Wiley-VCH: Weinheim, Germany, 2005; pp 45-109.
[3] S. Hanessian, M. Simard, S. Roelens, J. Am. Chem. Soc.
1995, 117, 7630 – 7645.
[4] J. L. Sessler, P. A. Gale, W. S. Cho, Anion Receptor Chemistry, RSC Publishing, UK,
2006.
Synthesis of Peptoid-containing Macrocycles by Multiple Ugi-type
Multicomponent Reactions
Daniel G. Rivera and Ludger A. Wessjohann*
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3,
06120, Halle/Saale, Germany. Fax: +49 345 5582 1309; Tel: +49 345 5582 1301; E-mail:
wessjohann@ipb-halle.de
PSA 56
A versatile strategy towards peptoid-containing macrocycles, termed multiple multicomponent
macrocyclizations including bifunctional building blocks (MiBs), has been recently developed. [1]
In this approach, the building blocks are allowed to undergo a cyclooligomerization process
based on multiple Ugi four-component reactions (Ugi-4CR) to afford macrocycles including
varied peptoid moieties. [1] Macrocycles of different sizes, shapes, and presenting varied
functional appendages have been produced in one pot by implementing the different
combinations of bifunctional building blocks. [1,2] The rapid generation of skeletal and appendage
diversity is a key feature of this approach, which enables the creation of parallel and
combinatorial libraries of macrocycles with very low synthetic cost. [2]
An extension of the MiB methodology to the third dimension allowed to obtain peptoidcontaining
cryptands, cryptophanes, and steroid-based cages. [2a,3] This procedure comprises
the performance of threefold Ugi-4CR-based macrocyclizations to assemble the macrobicyclic
frameworks in one pot. The peptide-like skeletons and the variable functional appendages make
these compounds amenable for applications in catalysis, coordination and supramolecular
chemistry.
[1] a) L. A. Wessjohann, B. Voigt, D. G. Rivera, Angew. Chem. Int. Ed., 2005, 44, 4785-4790;
b) L. A. Wessjohann, E. Ruijter, Mol. Diversity, 2005, 9, 159-169.
[2] a) D. G. Rivera, O. E. Vercillo, L. A. Wessjohann, Synlett, 2007, 308-312; b) L. A.
Wessjohann, D. G. Rivera, F. Coll, J. Org. Chem., 2006, 71, 7521-7526.
[3] D. G. Rivera, L. A. Wessjohann, J. Am. Chem. Soc. 2006, 128, 7122-7123.