Novel Aspects on the Preparation of Spirocyclic and Fused Unusual β-Lactams

Abstract

β-Lactam antibiotics have occupied a central role in the fight against pathogenic bacteria and the subsequent rise in quality of life for the world population as a whole. However, the extensive use of common β-lactam antibiotics such as penicillins and cephalosporins in medicine has resulted in an increasing number of resistant strains of bacteria through mutation and βlactamase gene transfer. The resistance of bacteria to the classical β-lactam antibiotics can be overcome, e.g., by using novel β-lactam moieties in drugs which show much higher stability towards these resistance bacteria. In addition, there are many important nonantibiotic uses of 2azetidinones in fields ranging from enzyme inhibition to gene activation. These biological activities, combined with the use of these products as starting materials to prepare αand β-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest, provide the motivation to explore new methodologies for the synthesis of substances based on the β-lactam core. The aim of this chapter is to provide a survey of the types of reactions used to prepare non-conventional spirocyclic and fused β-lactams, concentrating on the advances that have been made in the last decade, and in particular in the last five years. We will draw special attention to radical cyclizations, cycloaddition reactions, and transition metal-catalyzed reactions.

Variable-Sized bis(4-spiro-fused-β-lactam)-Based Unsaturated Macrocycles: Synthesis and Characterization

“…Among azaheterocyclic ring systems, C3 and C4 spiro-fused β-lactams (azetidin-2-one) (Figure ) − are uniquely important for their presence in a family of marine natural products, e.g., chartellines and chartelamides, for their prominence in synthetic chemistry as versatile building blocks in the synthesis of α/β-amino acids, alkaloids, heterocycles, toxoids, and other relevant molecular structures and for their medicinal chemistry in synthesis of many biologically vital materials that behave as β-turn mimetics, enzyme inhibitors, and precursors of α,α-disubstituted β-amino acids, as well as their biological activities including antibacterial agents, active against HIV-1 and plasmodium, along with cholesterol absorption inhibitors …”

Sequential Diimination, Staudinger [2 + 2] Ketene–Imine Cycloaddition, and Ring-Closing Metathesis (RCM) Reactions: In Route to Bis(4-spiro-fused-β-lactams)-Based Macrocycles

“…Generally, the synthesis, chemistry, and biological activity of C3 and C4 spiro-fused 2-azetidinones (Figure ) have gained great interest over the years, which is evident from their increasing number of publications in literature. − The spirocyclic β-lactam center has been fruitfully explored in the synthesis of many biologically important compounds that behave as β-turn mimetics, enzyme inhibitors, and precursors of α,α-disubstituted β-amino acids (Figure ). As well to this, C4 spiranic β-lactam center presents in a family of marine natural products, namely chartellines and chartelamides (Figure ).…”

Microwave-Induced Synthesis of Enantiopure β- Lactams

“…They were used as promising inhibitors of serine protease [4] and acyl coenzyme A cholesterol transferases (ACAT) [5]. These types of molecules were the key substrates for the preparation of various heterocycles of biological and pharmacological significances [6]. Hydroxy beta-lactam derivatives were the crucial fragments in the semi-synthesis of anticancer drug, Taxol and Taxotere [7].…”