John M. Nuss

Alkylation of Rink's amide linker on polystyrene resin: A reductive amination approach to modified amine-linkers for the solid phase synthesis of N-substituted amide derivatives

Reductive amination of aldehydes and ketones using sodium cyanoborohydride and Rinks 4-(2′,4′-dimethoxyphenyl-aminomethyl)-phenoxymethyl-linked polystyrene resin [Rinks amine linker on copoly-(styrene-1%-divinylbenzene)]1 2 affords high yields of linker-bound, N-alkyl amines with excellent chemical selectivity. Subsequent coupling with acid derivatives gave derivatized N-substituted amides in excellent yields after cleavage from the solid-support.

Utilization of Fukuyama’s sulfonamide protecting group for the synthesis of N-substituted α-amino acids and derivatives

Abstract A novel and general route for the solid phase synthesis of N -substituted α-amino acids has been developed. This synthesis employs Fukuyamas 2-nitrobenzenesulfonamide protecting group for preparation of secondary amines. The versatility of this methodology is demonstrated by the facile synthesis of a trisubstituted diketopiperazine (DKP) skeleton.

Developing a general strategy for the solid supported synthesis of heterocycles: Applications to the generation of molecular diversity and drug discovery

The development of a general strategy for the generation of molecular diversity in the form of novel, non-amide based heterocyclic structures is described. The generation of diverse peptide and peptidomimetic libraries, the automation of these strategies and computational approaches to diversity generation are also discussed. The main focus of this lecture is the the progression of these concepts into a strategy for small molecule library generation, and hence the generation of small molecule therapeutic leads.

Solid phase synthesis of β-lactams via the Staudinger reaction

Abstract The synthesis of cis-azetidinones on solid support via the Staudinger reaction is described. The final products are obtained in high purity with no purification required.

Solid and solution phase synthesis of α-keto amides via azetidinone ring-opening: Application to the synthesis of poststatin

Abstract 3,3-Diethoxy-N-sulfonyl and carbamoyl azetidin-2-ones undergo efficient ring-opening reaction with various amine nucleophiles. Subsequent acid hydrolysis of the ketal moiety generated α-keto amides in excellent overall yields. The naturally occurring serine protease inhibitor poststatin was synthesized using this ring-opening reaction as the key step.