In this study, we report the development of efficient synthetic strategies for the preparation of novel 2'-carboxyl isoflavones and their recyclization products, pyrazoles and oxazoles. Utilizing ...readily accessible starting materials and mild reaction conditions, the synthesis affords valuable compounds with good to excellent yields. The presence of diverse functional groups, including hydroxyl, carboxyl, and carboxamido moieties, renders these molecules attractive for biological screening and targeted structural modifications. This work unveils new avenues for the design of compounds exhibiting a wide range of beneficial properties and opens new opportunities for future research into intramolecular interactions of proximal functional groups.
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•A series of (spiro)pyranocoumarin oximes were successfully subjected to Beckmann rearrangement in the presence of PPA.•The rearrangement led to the efficient formation of unusual ...imines as major products via 2,3-alkyl migration.•The expected lactams were obtained as minor products with insignificant yields via 1,2-alkyl migration.•These findings demonstrate a new approach for the selective synthesis of complex and diverse imines with potential applications in synthetic organic chemistry and medicinal chemistry.
This paper presents the successful implementation of Beckmann rearrangement on a series of (spiro)pyranocoumarin oximes in polyphosphoric acid (PPA) medium. The method demonstrated excellent proficiency in the synthesis of unexpected imines as major products and amides as minor products. The labeled 15NH2OH·HCl control experiment yielded oxime and rearrangement products that incorporated the 15N label. Furthermore, we have proposed a possible rearrangement mechanism. NMR spectroscopy data (correlation HMBC and 15N NMR) confirmed the structure of the synthesized products. These findings provide a new and efficient approach for constructing complex imines with diverse applications in synthetic organic chemistry.
The aminomethylation of hydroxylated isoflavones with 2-aminoethanol, 3-amino-1-propanol, 4-amino-1-butanol, and 5-amino-1-pentanol in the presence of excess formaldehyde led principally to ...9-(2-hydroalkyl)-9,10-dihydro-4H,8H-chromeno8,7-e1,3-oxazin-4-ones 4 and/or the tautomeric 7-hydroxy-8-(1,3-oxazepan-3-ylmethyl)-4H-chromen-4-ones 5. The ratio of these tautomers was dependent on solvent polarity, electronic effects of aryl substituents in the isoflavone and the structure of the amino alcohol. NMR studies confirmed the interconversion of tautomeric forms.
The regioselective condensations of various 7‐hydroxyisoflavonoids with bis(N,N‐dimethylamino)methane in a Mannich reaction provided C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids in good ...yield. Similar condensations of 7‐hydroxy‐8‐methylisoflavonoids led to the C‐6‐substituted analogs. Thermal eliminations of dimethylamine from these C‐6 or C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids generated ortho‐quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho‐quinone methide intermediates trapped dienophiles including 2,3‐dihydrofuran, 3,4‐dihydro‐2H‐pyran, 3‐(N,N‐dimethylamino)‐5,5‐dimethyl‐2‐cyclohexen‐1‐one, 1‐morpholinocyclopentene, and 1‐morpholinocyclohexene to give various inverse electron‐demand Diels–Alder adducts. Several adducts derived from 8‐N,N‐dimethylaminomethyl‐substituted isoflavonoids displayed good activity in the 1–10 μm concentration range in an in vitro proliferation assay using the PC‐3 prostate cancer cell line.
Thermally generated ortho‐quinone methides from Mannich bases of 7‐hydroxyisoflavones or from 8‐methoxymethyl‐ or 8‐hydroxymethyl 7‐hydroxyisoflavones trapped a variety of electron‐rich dienophiles to give various inverse electron‐demand Diels–Alder adducts in good yields. Selected adducts displayed good activity in a proliferation assay using the PC‐3 prostate cancer cells.
This study explores the synthesis of a diverse series of linear (spiro)pyranocoumarins and their corresponding oximes, compounds known for their promising biological activities. Building on previous ...work, the authors expand the array of target compounds, adding structural features such as dimethyl groups and various cycloaliphatic rings. The novel synthetic procedure applied herein couples o-hydroxyacetyl coumarins with respective ketones via Kabbe condensation, yielding 16 derivatives, including 12 new compounds. A further step engages these (spiro)pyranocoumarins with hydroxylamine hydrochloride, leading to oximes, selectively at the exocyclic oxygen atom of the chroman-4-one fragment. Optimizing synthesis conditions has increased product yields and reduced reaction times. Acidic hydrolysis of select compounds introduces additional carbonyl groups and facilitates deprotection, while the subsequent reaction with hydroxylamine hydrochloride produces dual-oxime compounds. These findings contribute to the ongoing development of pyranocoumarin and oxime-based therapeutics, with potential applications in treating various diseases
The propensity of cyclic carboxylic anhydrides to undergo ring‐opening was exploited in a reaction with 2'‐hydroxy‐α‐heteroarylacetophenones leading to the formation of chromones. New simple method ...was developed for the synthesis of 2‐(ω‐carboxyalkyl)‐3‐heteroarylchromones without protecting either the phenolic or the carboxylic groups. Treatment with hydrazine led to the formation of 3(5)‐(ω‐carboxyalkyl)‐5(3)‐(2,4‐dihydroxyphenyl)‐4‐heteroarylpyrazoles.
This research presents a highly efficient method for synthesizing diverse aminomethylcoumarin libraries through the interaction of Mannich bases of coumarins and primary amines. The developed ...amination process demonstrated versatility and compatibility with various substituents. Reactions were completed within short timeframes, yielding high-purity products with substantial yields, as well as facilitating the scale-up of the process. The synthesized derivatives exhibited structural diversity, incorporating carboxylic and amino groups, as well as amide, hydrazide, and hydroxamic acid moieties. In silico ADME predictions highlighted the potential of these aminomethylcoumarins as promising candidates for further optimization in the development of oral chemotherapeutic agents
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•Efficient approach to enaminoketones of 2′-carboxamidodeoxybenzoins in good yields.•Efficient approach to otherwise not readily obtainable 3-aryl-4-formylisocoumarins.•Readily ...available reagents, simple procedures, and short reaction times.•N,N-Dimethylformamide dimethyl acetal serves both as a carbon source and solvent.
The efficient synthesis of enaminoketones of 2′-carboxamidodeoxybenzoins and subsequent transformation into 1-oxo-3-aryl-1H-isochromene-4-carbaldehydes via an intermolecular cyclization under weakly acidic conditions has been demonstrated. Mild reaction conditions, a simple work-up procedure, short reaction times and high yields are the advantages of the presented method.
Flavonoids and their derivatives have historically been a source of therapeutic agents. Every year, more and more data is published on new flavonoid compounds, both synthetic and isolated from ...natural sources, and their innumerable physiological and pharmacological activities. This review presents synthetic routes towards 3-(carboxyphenyl)chromones and evaluation of their biological activity as published in both journal and patent literature. We have focused specifically on the 3-(carboxyphenyl)chromones, because while methods of synthesis and biological activity of 2(3)-substituted and 2,3-disubstituted chromones are well studied, literature data on isoflavones containing a carboxyl, ester, or amide group in ring B is scarce and fragmentary. The presented generalization of synthetic strategies and biological activity of 3-(carboxyphenyl)chromone derivatives demonstrates that this class of compounds can be targeted for discovery of new drugs and can be readily prepared owing to recent advances in synthetic organic and medicinal chemistry
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All six possible stereoisomers of calix4arenes with four different substituents on the lower rim of the macrocycle have been synthesized by stepwise alkylation of the hydroxyl groups ...of tert-butylcalix4arene using (R)- or (S)-1-phenylethylamide groups as chiral auxiliaries. They form three enantiomeric pairs, as confirmed by the values of their specific rotation.