Synthesis Of Novel Β-lactams Research Articles

Synthesis of novel β-lactams: Antioxidant activity, acetylcholinesterase inhibition and computational studies

A convenient synthesis of some novel β-lactam derivatives with interesting pharmacological activities was described. Some of the synthesized compounds exhibited excellent antioxidant activity and showed acetylcholinesterase inhibition. Theoretical studies were carried out on the most potent compounds 5a and 5b to compare their potential interaction with crystal structure of recombinant human acetylcholinesterase in complex with Donepezil (PDB ID: 4EY7) and binary complex of native hAChE with Donepezil (PDBID:6O4W). The comprehensive theoretical and experimental mechanical studies of compounds 5b were compatible with its FT-IR, 1H NMR,13C NMR and Mass spectral data. The optimized molecular structure and the harmonic vibrational frequencies were examined DFT/B3LYP/6–31G(d) and Hartree-Fock HF/6–31G(d) energies and the difference in bond length and energies between compounds 5a and 5b was confirmed via theoretical studies.

Monocyclic β-Lactam: A Review on Synthesis and Potential Biological Activities of a Multitarget Core.

A monocyclic ring in their structure characterizes monobactams, a subclass of β-lactam antibiotics. Many of these compounds have a bactericidal mechanism of action and acts as penicillin and cephalosporins, interfering with bacterial cell wall biosynthesis. The synthesis of novel β-lactams is an emerging area of organic synthesis research due to the problem of increasing bacterial resistance to existing β -lactam antibiotics, and, in this way, new compounds have been presented with several structural modifications, aiming to improve biological activities. Among the biological activities studied, the most outstanding are antibacterial, antitubercular, anticholesterolemic, anticancer, antiinflammatory, antiviral, and anti-enzymatic, among others. This review explores the vast number of works related to monocyclic β-lactams, compounds of great importance in scientific research.

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

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. The present review aims to highlight recent advancement made in C-3 functionalization of β - lactams. 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.

Synthesis of novel β-lactams and in vitro evaluation against the human malaria parasite Plasmodium falciparum

The use of three-component four-center Ugi reactions to afford the synthesis of novel β-lactams is described. Three series of compounds have been made using this reaction in combination with the Mannich reaction. All compounds formed are racemic mixtures and were tested against the chloroquine sensitive D10 strain of Plasmodium falciparum in an in vitro assay. All compounds showed low to moderate microMolar range activity with the most active compounds 2.6 and 3.1 showing IC50 values 16 μM and 15 μM respectively

Synthesis of novel β-lactams bearing an anthraquinone moiety, and evaluation of their antimalarial activities

A novel series of β-lactams bearing an anthraquinone moiety have been synthesized from imines derived from anthraquinone-2-carbaldehyde and ketenes by a [2+2] cycloaddition reaction. The cycloadducts were fully characterized and evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain and showed moderate to excellent EC50 values varying from 9 to 50 μM.

Asymmetric synthesis of anticancer β-lactams via Staudinger reaction

This study describes the symmetric synthesis of novel β-lactams derived from chrysene directed towards their SAR, as well as their biological activities against several cancer cell lines in vitro. To our knowledge, this is the first report on the synthesis and biological evaluation of optically active anticancer β-lactams. That these anticancer effects are not uniform against all tumor lines suggests that the target of the action of these compounds is highly specific.

Asymmetric synthesis of anticancer β-lactams via Staudinger reaction

This study describes the symmetric synthesis of novel β-lactams derived from chrysene directed towards their SAR, as well as their biological activities against several cancer cell lines in vitro. To our knowledge, this is the first report on the synthesis and biological evaluation of optically active anticancer β-lactams. That these anticancer effects are not uniform against all tumor lines suggests that the target of the action of these compounds is highly specific.

Stereocontrolled synthesis of anticancer β-lactams via the Staudinger reaction

Stereocontrolled synthesis of novel β-lactams using polyaromatic imines following the Staudinger reaction has been accomplished. The effects of domestic microwave irradiation on this type of reaction have been investigated. Formation of trans-β-lactams has been explained through isomerization of the enolates formed during the reaction of acid chloride (equivalent) with imines in the presence of triethylamine. A donor–acceptor complex pathway is believed to be involved in the formation of cis-β-lactams. The effect of a peri hydrogen has been found to be significant in controlling the stereochemistry of the resulting β-lactams. SAR has identified β-lactams with anticancer activity. The presence of an acetoxy group has proven obligatory for their anticancer activity.

Alkene metathesis in the synthesis of novel β-lactams

Both monocyclic and bicyclic β-lactams systems are prepared via alkene metathesis reactions using Mo(CHC-Me2Ph)(NC6H3Pr2i-2,6)[OCMe(CF3)2]2 or Ru(HPh)-Cl2(PCy3)2.