ISMSC 2007 - Università degli Studi di Pavia

PSB 47
Dynamic Combinatorial Chemistry Applied to the Synthesis of Cyclopeptidic
Receptors for Anion Recognition in Aqueous Solutions
Zaida Rodriguez-Docampo, a Carsten Reyheller, b Stefan Kubik b and Sijbren Otto a
a, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, UK.
b, Fachbereich Chemie-Organische Chemie, Technische Universität Kaiserslautern, Erwin-
Schrödinger Strae, D-67663, Germany.
e-mail: zr212@cam.ac.uk
Dynamic combinatorial chemistry has proven to be a powerful tool in the design of complex
molecular receptors [1]. The application of disulfide exchange dynamic combinatorial chemistry
to modified cyclopeptides of the efficient receptor 1 [2] has led to the isolation of a new series of
receptors for anions in aqueous mixtures [3]. Structural and thermodynamic data of the binding
properties of the receptor 2c has demonstrated that the hydrophobic interactions within the
receptor reinforce the ligand complexation [4]. Taking advantage of this special feature of the
system and introducing more covalent linkages between the two cyclopeptide rings to get more
preorganised receptors, an enhancement of anion coordination is expected. With this purpose,
cyclopeptide 3 has been synthesised and screened with several spacers and anions. Some
preliminary promising results have been obtained.
The challenge of this project is not only to synthesise new efficient and selective receptors for
anions but also make them more soluble in water to make the recognition processes compatible
with biological systems.
O N O
N
NH
HN
N
O
O
N
N
O N N
H
O
1
N
O
N
HN
O
O
H
N
N
O
N
O
NH
N
N
O
X
2a, X=
2b, X=
2c, X=
N
HN
O
O
N
N
S S
OH
S S
S S
N
H
O
N
O
N
O
NH
N
O
O
HN
O
N
N
N
O
N
N
H
O
N
S
NH
N
S
O
O
3
O
HN
O
S
N
S
N
O
H
N
N
O
N
O
NH
N
N
O
[1] For a recent review see: PT. Corbett, J. Leclaire, L. Vial, KR. West, JKM. Sanders,
S. Otto. Chem Rev. 2006, 106, 3652-3711.
[2] S. Kubik, R. Goddard, R. Kirchner, D. Nolting, J. Seidel. Angew. Chem. Int. Ed. 2001, 40,
2648-2651.
[3] S. Otto, S. Kubik. J. Am. Chem. Soc. 2003, 125, 7804-7805.
[4] Z. Rodríguez-Docampo, S.I. Pascu, S. Kubik, S. Otto. J. Am. Chem. Soc. 2006, 128, 11206-
11210.
A [2]-Rotaxane from a Nickel Active-Metal Template
Pauline Fitzsimmonds, Stephen. M. Goldup, Nicholas. D. Gowans, David. A. Leigh and Vicki E.
Ronaldson.
School of Chemistry, University of Edinburgh, the King’s Buildings, West Mains Road,
Edinburgh, EH9 3JJ. (v.e.ronaldson@sms.ed.ac.uk)
Recently we have developed a strategy for the synthesis of rotaxanes in which the metal plays
a dual function: (i) acting as a template for entwining or threading the precursors; and (ii)
catalysing covalent bond formation between the reactants through the cavity of the macrocycle
to form a rotaxane [1].
Following a literature precedent for the Ni(II)-mediated homocoupling of acetylenes [2], we have
adapted this methodology to produce a nickel ‘active-metal template’ rotaxane synthesis.
(Scheme 1).
Scheme 1. A Ni(II)-mediated homocoupling to give a [2]-rotaxane.
PSB 48
The reaction gives high yields (up to 72%) with a 2:1 ratio of stopper to metal-macrocyclic
complex, making it highly atom efficient. In addition, Ni(II) reagents are cheap, relatively air
stable and easy to remove following reaction. The reaction has been shown to be tolerant to
both propargylic ethers and aryl alkynes, proving its versatile nature and the potential for
extension to heterocouplings, which we plan to investigate as the next step.
[1] V. Aucagne, K. D. Hänni, D. A. Leigh, P. J. Lusby and D. B. Walker, J. Am. Chem. Soc.,
2006, 128, 2186-2187.
[2] E. H. Smith and J. Whittall, Organometallics, 1994, 13, 5169-5172.