Library carbodiimides

Supported reagents have found application in many areas of synthesis including the construction of small peptides, the traditional foundation stone of solid phase synthesis. For example a recent paper describes the preparation of dipeptide p-nitroanilide and phosphonate libraries by supported carbodiimide coupling and scavenger purification (Scheme 2.52) [79]. 

In the initial carbodiimide research the valuable contributions of Prof. Dr W. von Eggers-Doering of Harvard University are acknowledged, and special thanks go to Prof. Dr D.M. Crothers, the former Chairman of the Chemistry Department of Yale University in New Haven, Connecticut, who allowed my access to Yale s fine technical libraries, which helped immensely in the compilation of the literature to this book. 

The synthesis of an 88-membered combinatorial library 24 based upon the natural product 25 was reported by Nesterenko et al. in their search for small molecules that selectively induce apoptosis in cancer cells. The key amide bond-forming reaction was performed in parallel using a polymer-supported carbodiimide as the dehydrating agent. 

An application of artificially imparted molecular recognition [79] is shown in Figure 13. A small model library (six discretes) of aminoketones was obtained by Moffatt oxidation of hydroxyethylamines using dichloroacetic acid in DMSO and the tertiary amine-tagged EDC as a carbodiimide. After 24 h at room temperature, the sulfonic acid resin 3 and the tertiary amine resin 2 were added, the mixtures were stirred for 20 h, and the resulting solutions contained the pure library components (yields from 48% to 91%, HPLC purities around 90%) with no diimide or urea or dichloroacetic acid left. While resin 2 acted as a molecu-... 

A hydantoin library of 800 compounds has been reported by Dress-mann et al. [61]. In this approach, 20 different amino acids and over 80 primary amines were incorporated. Selected amino acids were attached via their iV-terminus to hydroxymethyl polystyrene resin by using a carbamate linker. This enabled generation of the free acid resin-bound intermediates, which could then be converted to their corresponding amides by standard carbodiimide coupling reactions and excess primary amine. Concomitant... 

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