Synthetic Approaches toward Monocyclic 3‐Amino‐β‐lactams

Abstract

Due to the emerging resistance against classical β‐lactam‐based antibiotics, a growing number of bacterial infections has become harder to treat. This alarming tendency necessitates continued research on novel antibacterial agents. Many classes of β‐lactam antibiotics are characterized by the presence of the 3‐aminoazetidin‐2‐one core, which resembles the natural substrate of the target penicillin‐binding proteins. In that respect, this Review summarizes the different synthetic pathways toward this key structure for the development of new antibacterial agents. The most extensively applied methods for 3‐amino‐β‐lactam ring formation are discussed, in addition to a few less common strategies. Moreover, approaches to introduce the 3‐amino substituent after ring formation are also covered.

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

“…A large number of nitrogencontaining saturated cyclic compounds are known as antibiotics, analgesics, antidepressants, anticancer, anti-HIV, and anti-HCV agents. [1][2][3] According to the medicinal chemistry literature, there are two main fields of interest with respect to the structures of the present drug candidates: the popularity of organofluorine scaffolds and of azaheterocycles. [4][5][6][7][8][9] Saturated N-heterocycles are building blocks in synthetic bioactive products and medicinal compounds.…”

“…In the development of new pharmaceuticals three-dimensional, functionalized scaffolds with saturated building blocks, especially saturated N-heterocycles, are used preferably. [1][2][3] Figure 1 shows some representative N-heterocyclic structures with biological relevance. [10][11][12][13][14] Fluorine-containing organic molecules (except only a few representatives) are practically absent in nature, but they have received significant interest in drug research.…”

“…Taking into consideration of the high biorelevance of saturated N-heterocycles [1][2][3][4][5][6][7][8][9] and organofluorine molecules, [15][16][17] the combination of these molecular structures is a hot topic in synthetic and medicinal chemistry. The synthetic methods…”

Chemodiscrimination of Olefin Bonds Through Cross‐Metathesis Reactions – Synthesis of Functionalized β‐Lactam and β‐Amino Acid Derivatives

“…applications of functionalized -lactams [25][26][27][28][29][30][31][32] or some fused bicyclic -lactams. [33][34][35][36][37][38][39] For example, opening of the azetidinone ring of various -lactam derivatives is considered to be one of the most convenient pathways for the stereocontrolled synthesis of open-chain or cyclic 2,3 -amino acid derivatives.…”

Synthesis and reactivity of 4-(trifluoromethyl)azetidin-2-ones

“…In addition to their well-known significance as antibacterial agents, β-lactams have been attracting considerable interest as building blocks and valuable intermediates from a synthetic point of view as well [11]. Because of the high ring strain associated with the four-membered ring system, β-lactams represent prominent substrates susceptible to ring-opening and ring-transformation reactions en route to a variety of nitrogen-containing acyclic and heterocyclic compounds [11][12].…”