Detailed project information

Nitrogen heterocycles of different ring sizes, with different substitution patterns and embedded in various molecular frameworks constitute extremely important structure classes in the search for bioactivity. Despite the large availability of methods to construct nitrogen heterocycles, there is still a strong need to further explore synthetic methods to efficiently synthesize novel heterocyclic structures, either in racemic, but preferentially in enantiomerically pure form. This proposal aims at the development of novel methodology for the synthesis of nitrogen heterocyclic structural motifs, based on biologically relevant natural products. The aim can be divided into two related objectives:

1. Synthetic applications of alkoxyallenes in the synthesis of nitrogen heterocycles

In the past few years we have identified alkoxyallenes as useful compounds for heterocycle synthesis. Given the importance of nitrogen heterocyclic structures in different classes of natural products with potent biological activity, this part of the project aims at further exploring the synthetic scope of alkoxyallenes in the formation of functionalized nitrogen heterocycles.

2. Exploration of N,N-acetals as versatile precursors for N-acyliminium ion chemistry

Recently, we have shown that N,N-acetals can be efficiently used as entirely novel precursors for the generation of N-acyliminium ions, which are versatile intermediates in the synthesis of nitrogen heterocycles. This part of the project aims at exploring the scope and limitations of N,N-acetals in CC-bond formation processes and apply the newly developed methodology in the synthesis of various classes of heterocyclic natural products. A most challenging class of natural products that will be addressed are the chaetoglobosins, highly functionalized heterocyclic compounds with relevant biological activity.

Articles

• dr. B.H.M. Kuijpers, dr. M. IJsselstijn, dr. F.L. van Delft, dr. S. Groothuys, Drs. ing. S.A.M.W. van den Broek, Prof. dr. F.P.J.T. Rutjes (2008). Ring-Closing Alkyne Metathesis in the Synthesis of Alkyne-Linked Glycoamino Acids.. Synlett. pp. 111-115
• drs. M.A.H. Moelands, dr. F.L. van Delft, Drs. K.F.W. Hekking, Prof. dr. F.P.J.T. Rutjes, Dr. D.C.J. Waalboer (2008). A Ring-Closing Metathesis Approach to Cyclic a,b-Dehydroamino Acids. Advanced synthesis & catalysis. pp. 95-106
• drs. D.C.J. Waalboer, Dr. F.L. van Delft, Prof. dr. F.P.J.T. Rutjes, Dhr. M.C. Schaapman (2008). High pressure enty into Platencin. Angewandte Chemie-International Edition. pp. 6576-
• F.P.J.T. Rutjes, F.L. van Delft, S.S. van Berkel, J.C.M. van Hest, M.F. Debets, S. Schoffelen (2009). Aza-dibenzocyclooctynes for fast and efficient enzyme PEGylation via copper-free (3+2) cycloaddition. Chem Commun. pp. 97-99
• F.L. van Delft, D.C.J. Waalboer, H.A. van Kalkeren, F.P.J.T. Rutjes, M.C. Schaapman (2009). Total Synthesis and Absolute Stereochemistry of Integric Acid. J Org Chem. pp. 8878-8881
• B. Ritzen, F.P.J.T. Rutjes, F.L. van Delft, M.C.M. van Oers (2009). Enantioselective Chemoenzymatic Synthesis of trans-Aziridines. J Org Chem. pp. 7548-7551

Proefschriften

• Dr. B. Ritzen (2011). Chemoenzymatic formation of biologically relevant nitrogen heterocycles. Radboud Universiteit Nijmegen. promotiedatum 10-11-2011. ISBN 978-90-9026230-7.
• Dr. D.C.J. Waalboer (2011). Synthetic studies on terpene natural products. Total synthesis of platencin, dehydrohomoplatencin and integric acid. Radboud Universiteit Nijmegen. promotiedatum 21-2-2011. ISBN 978-90-9025965-9.