ABSTRACT
A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.
Subject(s)
Anti-Bacterial Agents , Indoles , Microbial Sensitivity Tests , Molecular Docking Simulation , Schiff Bases , beta-Lactams , Schiff Bases/chemistry , Schiff Bases/pharmacology , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , beta-Lactams/chemistry , beta-Lactams/pharmacology , beta-Lactams/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Ketones/chemistry , Ketones/pharmacology , Ketones/chemical synthesis , Ethylenes/chemistry , Ethylenes/pharmacology , Stereoisomerism , Selenium/chemistry , Selenium/pharmacology , Sulfur/chemistry , Dose-Response Relationship, DrugABSTRACT
BACKGROUND: A lot of advancement has been made in the area of ß-lactams in recent times. Most of the research is targeted towards the synthesis of novel ß-lactams, their functionalization and exploring their biological potential. The C-3 functionalization of ß-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 ß-lactams. OBJECTIVE: The present review aims to highlight recent advancement made in C-3 functionalization of ß - lactams. CONCLUSION: To summarize, functionalization of ß-lactams at C-3 is an essential aspect of ß-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 ß-lactam heterocycles which provides a wide range of ß-lactams viz. 3-alkylated ß-lactams, 3-aryl/heteroarylated ß-lactams, 3- alkoxylated ß-lactams. On the other hand, base mediated functionalization of ß-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-ß-lactams also emerged as interesting methods for the synthesis of functionalized ß-lactams having good yields and diastereoselectivities.
Subject(s)
beta-Lactams/chemical synthesis , Alkylation , Molecular Structure , StereoisomerismABSTRACT
Roses are one of the most important groups of ornamental plants and their fruits and flowers are used in a wide variety of food, nutritional products and different traditional medicines. The antioxidant activity of methanolic extracts from fresh flowers of three rose species (Rosa damascena, Rosa bourboniana and Rosa brunonii) was evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free-radical method. The ability to scavenge DPPH radical was measured by the discoloration of the solution. The methanolic extract from R. brunonii exhibited maximum free-radical-scavenging activity (64.5+/-0.38%) followed by R. bourboniana (51.8+/-0.46%) and R. damascena (43.6+/-0.25%) at 100 microg/ml. Simultaneously, ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was used to study phenolic composition in the methanolic extracts from the fresh flowers of rose species. The phenolic constituents were further investigated by direct infusion-ESI-QTOF-MS/MS in negative ion mode. Characteristic Electrospray ionization tandem mass spectrometry (ESI-MS/MS) spectra with other diagnostic fragment ions generated by retro Diels-Alder (RDA) fragmentation pathways were recorded for the flavonoids. Distinct similarities were observed in the relative distribution of polyphenolic compounds among the three species. The dominance of quercetin, kaempferol and their glycosides was observed in all the three species.