Van der Eycken Erik


Department of Chemistry Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC) University of Leuven (KU Leuven) Celestijnenlaan 200F, B-3001 Leuven Belgium

Abstract:

Medium-sized rings are abundantly present in many biologically active (natural) products as e.g. the alkaloids aphanorphine, lennoxamine and cephalotaxine and the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist Dizocilpine, also known as MK-801. However, the synthesis of medium-sized rings is known to be rather cumbersome and no good generally applicable procedures have been described so far.¹ Some time ago we have elaborated an efficient synthesis of the 3-benzazepine framework via an intramolecular Heck reductive cyclization.² We have demonstrated that the application of microwave irradiation is beneficial for this process. As a result of these investigations we extended our research towards the synthesis of indoloazocines, dibenzoazocines, dibenzoazepines, 3-benzazepines and dibenzo[c,e]azepinones.³ To assure the generation of diversity we utilized multicomponent reactions as the aldehyde/amine/alkyne (A3) coupling⁴ and the Ugi 4CR⁵, which was run in an intramolecular fashion. The beneficial effect of the application of microwave irradiation in each of these processes will be commented.

Biologically active medium-sized ring compounds:

REFERENCES:

• Microwave-Assisted Synthesis of Medium-Sized Heterocycles, A. Sharma, P. Appukkuttan, E. Van der Eycken, Chem. Comm., 48, 1623 - 1637, 2012.        
• Efficient Synthesis of the 3-Benzazepine Framework via Intramolecular Heck Reductive Cyclization, P. A. Donets, E. Van der Eycken, Org. Lett., 9, 3017-3020, 2007.
• Diversity-Oriented Microwave-Assisted Synthesis of the 3-Benzazepine Framework, V. A. Peshkov, O. P. Pereshivko, P. A. Donets, V. P. Mehta, E. V. Van der Eycken, Eur. J. Org. Chem., 25, 4861-4867, 2010, and references cited.
• A walk around the A3-coupling reaction and related protocols, V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Chem. Soc. Rev., 41, 3790 - 3807, 2012.
• A Microwave-Assisted Diastereoselective Multicomponent Reaction to Access Dibenzo[c,e]azepinones : Synthesis and Biological Evaluation, V. P. Mehta, S. G. Modha, E. Ruijter, K. Van Hecke, L. Van Meervelt,  C. Pannecouque, J. Balzarini, R. V. A. Orru, E. Van der Eycken, J. Org. Chem., 76, 2828–2839, 2011.