Girija S. Singh

Recent progress in synthesis and bioactivity studies of indolizines.

The present review describes the recent progress in synthetic approaches to construct indolizine framework (including partially or wholly reduced ring) and the design of such compounds with potential biological activity. The methods of synthesis are classified as the Tschitschibabin reaction, 1,3-dipolar cycloadditions, cyclisation reactions depending on the position of bond formation, and other methods. The biological activities include antimicrobial activity, antioxidant activity, anti-inflammatory activity, anticonvulsant activity, enzymes inhibition activity and activity as calcium entry blocker. Consequently this review emphasizes the significant development in synthetic methods of indolizines during the current decade, and the importance of indolizines in drug discovery.

Azetidines, Azetines and Azetes: Monocyclic

The four-membered azaheterocycles, azetidines and azetidin-2-ones are thermally stable and easy to handle. Structures of many compounds have been established by X-ray crystallography. Azetidines react with electrophiles and nucleophiles. The ring opening affords useful amides, alkenes, and amines. Cyclic products such as piperidines, pyrrolidines, and pyrroles have been synthesized from azetidines. Oxidation of 3-hydroxyazetidines forms azetidin-3-ones. Azetidines are synthesized from acyclic precursors like γ-haloamines, γ-aminoalcohols, and β-aminoallenes. Reactions of 1,3-dielectrophiles with primary amines and cycloadditions are also used in the synthesis of azetidines. Reduction of β-lactams affords azetidines. Heterocycles like aziridines, oxetanes, and azabicyclobutanes are transformed into azetidines. Azetidin-2-ones (β-lactams) are precursors of β-amino acids, amides, 3,3-dichloroazetidines, and many other heterocyclic compounds. The syntheses of β-lactams involve cyclizations of β-amino acids, β-amino esters, β-functionalized amides, and cyclocondensations of isocyanates and alkenes, imines and enolates, imines and ketenes, and nitrones and alkynes. The application of chiral auxiliaries and catalysts has made considerable progress in asymmetric synthesis. Applications of microwaves and polymer supports are reported. Although β-lactams are mainly antibacterials, many compounds have been tested and shown promising results as cholesterol absorption inhibitors (CAIs), enzyme inhibitors, anticancer agents, and hypoglycemic agents. A monocyclic azetidin-2-one (ezetimibe) is now in clinical use as CAI. Azetines and azetes comprise a rare class of constrained azaheterocycles. Only a few stable compounds belonging to these classes are known. Azetines undergo ring opening and cycloaddition reactions. Azetines are synthesized by photochemical cyclization of amides and by partial reduction of azetes. Tri-t-butylazete is a kinetically stabilized compound, which undergoes reduction, cycloaddition, and cycloreversion. It is synthesized by photolysis of pyridazines, and by thermolysis or photolysis of Dewar pyridazines.

Evaluation of some classical hydrazones of ketones and 1,2-diketones as antileishmanial, antibacterial and antifungal agents

The paper describes the synthesis and antimicrobial (antileishmanial, antibacterial and antifungal) activity of some classical hydrazones of benzophenones and of 1,2-diketones. N-(Diaryl) acyl derivatives of these hydrazones have also been synthesized and evaluated. 4,4,-Demthoxybenzil monohydrazone and 4,4′-dimethoxybenzophenone hydrazone showed significant antileishmanial activity. The effect of substituents on the bioactivity is discussed.

Synthesis of N-(1-methyl-1H-indol-3-yl)methyleneamines and 3,3-diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones as potential antileishmanial agents

A series of N-(1-methyl-1H-indol-3-yl)methyleneamines and eight new 3,3-diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones have been synthesized and screened for their antileishmanial activity against Leishmania major. 3,3-Diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones have been synthesized by the Staudingers ketene-imine cycloaddition employing two 2-diazo-1,2-diarylethanones as the precursors of diarylketenes. A marked improvement in anti-parasitic activity is observed by transformation of the methyleneamines to azetidin-2-ones in seven out of eight compounds. Two compounds displayed antileishmanial activity comparable to that of the clinically used antileshmanial drug, amphotericine B.

Xanthones and Anthranoids from the Medicinal Plants of Africa

Xanthones or xanthen-9H-ones (dibenzo-gamma-pirone) comprise an important class of oxygenated heterocycles whose role is well known in medicinal chemistry. The biological activities of this class of compounds are associated with their tricyclic scaffold but vary depending on the nature and/or position of the different substituents. In this chapter, the biosynthetic pathways of xanthones and anthrones (or anthronoids) are examined, and we summarize the occurrence of these two classes of compounds in African plants, together with their biological/pharmacological activities. It appears that most xanthones identified so far in plants of the continent were isolated from the family Guttiferae. The present literature review revealed 97 compounds (86 xanthones and 11 anthranoids), of which 46 were reported for the first time. The biological activity reported for such compound includes antimicrobial, cytotoxic, and enzyme inhibitory effects.

Recent applications of Cinchona alkaloid-based catalysts in asymmetric addition reactions

The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Antimicrobial, Crown Gall Tumor Inhibitory and Cytotoxicity Assays of N-[(1-methyl-1H-indole-3-yl)methylene]amines Synthesized by an Improved Protocol

The present paper reports an easy preparation of imines of N-methyl-1H-indole-3-carboxaldehyde by its condensation with alkyl and aromatic amines in ethanol without using any catalyst or dehydrating agent. The compounds have been screened for their antibacterial, antifungal, crown gall tumor inhibitory, and cytotoxic activities. As a major finding some of the compounds exhibited potential biological activity. The imine containing a 4-chlorophenyl group exhibits potential antitumor activity and brine shrimp lethality against crown gall tumor and brine shrimps, respectively. Furthermore, this imine containing a 4-chlorophenyl group also exhibits significant antifungal activity against Candida albicans fungal strains. The compound containing N-diphenylmethyl group has been observed most active against the Gram-positive bacteria.

Azetidin‐2‐one Versus Chroman‐2‐one: Application of 1H‐13C COSY NMR and Mass Spectroscopy in Structure Elucidation–Class of Compounds

Abstract Azetidin‐2‐ones, commonly known as β‐lactams, constitute a biologically important class of compound. Treatment of azetidin‐2‐ones with alkali is known to form diverse types of compounds depending on the stability of the ring. In many cases, the ring is retained in the product at the cost of transformation of substituents. Spectroscopy is the most important tool to characterize the organic compounds. However, in some cases the structures of the products are so closely related that simple IR, 1H NMR, and 13C NMR spectra do not lead to unambiguous structure elucidation. This article reports a novel application of 1H‐13C COSY NMR and mass spectroscopy in determining unequivocally an azetidin‐2‐one ring structure instead of a chroman‐2‐one ring structure for the product obtained by treatment of 1‐benzhydryl‐3,3‐bis(4‐methylphenyl)‐4‐[2‐(o‐dip‐tolylacyl)hydroxyphenyl]‐2‐azetidinone with ethanolic sodium hydroxide at room temperature.

Assignment of E–Z-configurations of spiro-oxirane-oxindoles synthesized by rhodium(II) acetate-catalyzed reaction of ethyl diazoacetate with N-methylisatin

ABSTRACT The rhodium(II) acetate [Rh2(OAc4)]-catalyzed reaction of ethyl diazoacetate with N-methylisatin leads to the formation of diastereomeric oxiranes spiro-fused to N-methyl-2-oxindole together with 1,3-dioxolane bis-spiro-fused to N-methyl-2-oxindole. The formation of ylide from the reaction of rhodium-carbenoid with C-3 carbonyl group of the N-methylisatin undergoing a 1,3-cyclization, and a [3 + 2]-dipolar cycloaddition with another molecule of N-methylisatin, respectively, explains the formation of products. The application of nuclear overhauser effect spectroscopy to determine the E–Z-configurations of the spiro-oxirane-oxindoles is demonstrated.

Chemoselective Reaction of Benzoylisothiocyanates with Hydroxyl Group of Salicylamide: a New and Convenient Entry Into 2-Aryl-4H-benzo[e][1,3]oxazin-4-ones

Abstract The reactions of benzoylisothiocyanates with salicylamide in pyridine-xylene solution occurs chemoselectively at the hydroxyl group of the salicylamide to afford the corresponding O-benzoyl derivatives. The latter products, on prolonged heating in pyridine-xylene solution, undergo cyclodehydration to give 2-aryl-4H-benzo[e][1,3]oxazin-4-ones in good yields. These compounds could also be synthesized by a direct one-pot reaction of benzoylisothiocyanates with salicylamide by slow addition of benzoylisothiocyanates into a solution of salicylamide in xylene-pyridine solution under reflux. The products have been characterized on the basis of satisfactory analytical and spectral data. GRAPHICAL ABSTRACT