A Comprehensive Review on C-3 Functionalization of β-Lactams

Abstract

Background: A lot of advancement has been made in the area of β-lactams in recent times. Most of the research is targeted towards the synthesis of novel β-lactams, their functionalization and exploring their biological potential. The C-3 functionalization of β-lactams has continued to attract considerable interest of the scientific community due to their utility as versatile intermediates in organic synthesis and their therapeutic applications. This has led to the significant increase in efforts towards developing efficient and economic strategies for C-3 functionalized β-lactams. Objective: The present review aims to highlight recent advancement made in C-3 functionalization of β-lactams. Conclusion: To summarize, functionalization of β-lactams at C-3 is an essential aspect of β-lactam chemistry in order to improve/modify its synthetic utility as well as biological potential. The C-3 carbocation equivalent method has emerged as an important and convenient strategy for C-3 functionalization of β-lactam heterocycles which provides a wide range of β-lactams viz. 3-alkylated β-lactams, 3-aryl/heteroarylated β-lactams, 3- alkoxylated β-lactams. On the other hand, base mediated functionalization of β-lactams via carbanion intermediate is another useful approach but their scope is limited by the requirement of stringent reaction conditions. In addition to this, organometallic reagent mediated α-alkylation of 3-halo/3-keto-β-lactams also emerged as interesting methods for the synthesis of functionalized β-lactams having good yields and diastereoselectivities.

Designed synthetic pathway of stereoselective novel monocyclic cis‐bis‐β‐lactams including a 1,3,4‐thiadiazole‐2,5‐dithiol constituent: Antimicrobial activity, molecular docking

“…Various work has been done on the synthesis and modification of β-lactams to increase their antimicrobial activities. The most tremendous significance of the β-lactams nucleus in the field of medicinal chemistry is the various synthetic procedures that have been reported for forming the β-lactams [21][22][23][24][25][26][27]. The most commonly used synthetic procedure is [2 + 2] cycloaddition ketene-imine, that is, Staudinger reaction [28][29][30].…”

Synthesis, Characterisation and Mechanism of Action of Anticancer 3-Fluoroazetidin-2-ones

“…Among the heterocyclic structures reported, the β-lactam ring has been explored in the design of CA-4 analogues as it provides a rigid scaffold for the CA-4 aryl rings, preventing the undesired conversion to the inactive trans isomer while maintaining the essential cis geometry between rings A and B of CA-4 and resulting in potent antimitotic compounds [31][32][33][34]. β-Lactam derivatives are versatile and attractive chemical scaffolds for drug discovery [35][36][37], and the β-lactam structure is a useful template for the design of novel anticancer agents [38]. Microtubule-targeting agents (MTAs) are among the most frequently prescribed antitumour chemotherapeutic agents.…”

Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands

“…N-thiolated monocyclic β-lactam derivatives and polyaromatic rings that contain βlactam ring have been identified as stimulators of tumorigenesis and inhibitors of tumor cell growth [45,46]. The most significant importance of the β-lactam containing moiety in the field of pharmacology is the diverse synthetic procedures that have been reported for forming the β-lactam derivatives [47][48][49][50][51][52][53].…”