beta-Lactams as synthons to biologically relevant molecules

This dissertation describes a series of studies relating to the use of beta-lactams as synthons to various biologically relevant molecules/architectures. Additional studies toward the synthesis of novel beta-lactams and hydantoin systems are also described.;In chapter 2, a novel synthetic sequence is described for the conversion of simple beta-keto esters into enantiomerically enriched beta-amino acids. The key features of this sequence include the addition of azide to the C3 position of beta-keto ester derived N-tosyloxy-beta-lactams through a concomitant nucleophilic addition/N-O bond reduction reaction, a mild CsF induced N1 benzylation of alpha-azido monobactams, the preparation of alpha-keto-beta-lactams through a novel four step sequence from the corresponding 3-azido-1-benzyl-beta-lactams, and TEMPO mediated ring expansion of these compounds to the corresponding N-carboxy anhydrides (NCAs). In addition, the synthesis, isolation, and characterization of unusual 3-imino and 3-chloramino-beta-lactams is reported.;In chapter 3, methodology for the enantioselective synthesis of differentially protected erythro alpha,beta-diamino acids from N-tosyloxy beta-lactams is reported. The requisite N-tosyloxy beta-lactams are readily available from simple beta-keto esters. The synthetic utility of the method is demonstrated through its application to the preparation of an analog of the antifungal cyclic peptide rhodopeptin B5.;Chapter 4 focuses on the synthesis of N3-tosyloxy hydantoins and efforts toward the development a concomitant nucleophilic addition/N-O bond reduction reaction for these systems.;In chapter 5, methodology for the conversion of glucuronic acid glycosides to novel bicyclic beta-lactams is described. Using this strategy, two novel templates suitable for use in combinatorial chemistry strategies for the construction of a number of interesting beta-lactam motifs have been prepared. Key features of this strategy include a diastereoselective Ferrier reaction of a glucuronic acid glucal, selective beta-lactam ring formation using a cyclic allylic alcohol, and a chemoselective benzylic oxidation.