A novel class of potent tubulin polymerization inhibitors journal of medicinal chemistry. The mild reaction condition involves the removal of more acidic benzylic proton, which leads to a relatively cheap, nontoxic, metalfree method for the synthesis of 3aryl4substituted coumarins. Synthesis of 2azetidinones substituted coumarin derivative article pdf available in journal of the serbian chemical society 7710. General procedures for the preparation of 4substituted 1,2,3triazole coumarin derivatives. An efficient and simple procedure for the synthesis of 4. Original article synthesis of some 2, 6bis 1 coumarin 2yl44substituted phenyl pyridine derivatives as potent biological agents r. Substitution on coumarin nucleus leads to the search for more potent compounds. Upon activation with manganese powder, a cobaltcatalyzed ch bond activation of coumarins with aryl halides or pseudohalides in the presence of carbon monoxide provides various 3aroylcoumarin derivatives under mild conditions. Synthesis, cytotoxic evaluation, and in silico studies of. Moreover, they mostly lead to coumarins with subsistent in the 3 or 4position 14. Synthesis of 4heteroarylsubstituted coumarins by suzuki. Among these compounds 34, 39, 40, 43, 62, 65, and 67 exhibited significant antiproliferative activity toward a panel of tumor cell lines at subnanomolar ic 50 values. Cux 2 xcl, br are found to be efficient catalysts 10 mol% for the pechmann condensation reaction of phenols and.
The incorporation group as a fused component into parent coumarin alters the property of parent coumarin and converts it into a more useful product6. An efficient zrcl 4 catalyzed onepot solvent free protocol for the synthesis of 4substituted coumarins. Synthesis of 4substituted coumarins via the palladiumcatalyzed crosscouplings of 4tosylcoumarins with terminal acetylenes and organozinc reagents cheminform 2001, 32 38, nono. A convenient synthesis of 3behzyl, 3benzyl 4substituted coumarins and their benzo derivatives. Triethylammonium hydrogen sulfate et3nhhso4 has been studied to be an efficient ionic liquid catalyst for the synthesis of biologically potent coumarin derivatives. The intramolecular cyclization of the esters of salicylaldehyde, o hydroxyacetophenones, methyl salicylate, and 2.
A good alternative for the synthesis of 3,4unsubstituted coumarins is the. Sharma a, a department of chemistry, university of delhi, delhi 17, india. Synthesis of novel click coumarins and biological evaluation rajesh babu k. For example, coumarin derivatives, which have many advantages such as the feasible synthesis and favorable bioavailability, were mainly. General and efficient route for the synthesis of 3,4. Efforts have been carried out to synthesize new 4substituted coumarins by novel approaches using selective bromination of active methylene group of the coumarin 4methyl acetates and utilized both the active sites, thus formed for the synthesis of the novel heterocycles substituted at 4position of the coumarins5. An efficient synthesis of 4substituted coumarin derivatives via a palladiumcatalyzed suzuki crosscoupling reaction. Synthesis of substituted coumarin derivatives and their. In this paper, a series of novel 4substituted coumarin derivatives were synthesized. Structure activity relationship sar studies reveal that the electron donor group at position.
Onepot synthesis has been developed for 4carboethoxybenzo h coumarins starting from. Synthesis of heteroaryl substituted benzoccoumarins. Palladiumcatalyzed siteselective crosscoupling reactions of 3bromo4trifloxycoumarin or 3bromo4tosyloxycoumarin provide an efficient and facile route for the synthesis of 3,4disubstituted coumarins, which include 3,4diarylcoumarins, 3amino4arylcoumarins, and 3aryl4aminocoumarins. Accordingly, diverse 4carboethoxybenzocoumarins can be synthesized in moderatetoexcellent 31. Design, synthesis and biological evaluation of novel 4.
Request pdf recent developments of c4 substituted coumarin derivatives as. Coumarins coumarin 2hchromen2 one is a fragrant organic chemical compound in the benzopyrone chemical class, which is a colorless crystalline substance in its standard state it is found naturally in many plants families. Iron powder 8 gm was added portion wise with stirring to a hot mixture of 8nitro7hydroxy4 methyl coumarin 4. Onepot synthesis of 4carboalkoxysubstituted benzoh. An efficient and practical procedure for the synthesis of 4substituted coumarins surya k. Synthesis of novel click coumarins and biological evaluation. The yields of coumarin derivatives obtained via this new protocol, were equal or higher than those using the conventional method and the reaction time was reduced to a few minutes. Present work details the synthesis of substituted coumarin. Coumarin is plant flavonoids widely distributed in nature.
Herein, we repor t the highly efficient to tal synthesis of five naturally occurring coumarins, as well as a synthetic 3,4unsubstitute d coum arin figure 1. Coumarin syntheses via pechmann condensation in lewis acidic chloroaluminate ionic liquid. Compound 65 showed potent antiproliferative ability ic50 values of 747 nm and retained full activity in multidrug resistant cancer cells. Synthesis and evaluation of 4substituted coumarins as. A wide range of 4aryloxy coumarins bearing diverse electronic properties with substituents on either the phenyl ring of the coumarin nucleus or the c 4 substituted aryloxy smoothly participated in the intramolecular cdc reaction under palladium catalysis, providing a diverse set of coumestans generally in good to excellent yields 7399%. The synthesis involves initial oxidation of naphthols to the intermediary 1,2naphthoquinones with 2iodoxyben. Synthesis of coumarin and pyrazolyl substituted pyrido 3,2. Twenty 3phenyl coumarins were synthesized in 8090% yields. Synthesis of novel coumarin derivatives and its biological. Synthesis of 4substituted coumarins via the palladiumcatalyzed crosscouplings of 4tosylcoumarins with terminal acetylenes and organozinc reagents the journal of organic chemistry. Design, synthesis and biological evaluation of novel indolebenzimidazole. Synthesis, 18fradiolabeling and apoptosis inducing. A convenient synthesis of 3behzyl, 3benzyl 4substituted.
The mild reaction conditions and the high efficiency of the ni0pcy 3 catalyst make it very useful in the synthesis of 4. Studies and research in industrial chemistry, school of chemical science, jnanasahyadri. Synthesis of substituted coumarins via bronsted acid mediated. Department of chemistry and biochemistry, texas tech university, lubbock, tx 794091061, usa article info article. Synthesis of 2azetidinones substituted coumarin derivative. Pdf coumarins an important class of phytochemicals. An efficient and practical procedure for the synthesis of 4substituted coumarins s. Among these compounds 34, 39, 40, 43, 62, 65, and 67 exhibited significant antiproliferative activity toward a panel of tumor cell lines at subnanomolar ic50 values. Coumarins are widely used as additives in food, perfumes.
A novel organozinc reagent 4coumarinylzinc bromide. Many of these compounds have proven to be active as antibacterial 57, antifungal, antiinflammatory, anticoagulant, antihiv and antitumor agents. A novel class of potent tubulin polymerization inhibitors. Synthesis of 4substituted coumarins via the palladiumcatalyzed crosscouplings of 4tosylcoumarins with terminal acetylenes and organozinc reagents. Research group biopolymersgreen chemistry, centre of expertise biobased economy, avans university of applied science. Synthesis of 4substituted coumarins via the palladiumcatalyzed cross couplings of.
Among them, ensaculine is a coumarin derivative containing piperazine ring with three atom linker, which slows down or prevents the progression of the neurodegradation and alzheimers disease. Synthesis and evaluation of antiproliferative and src kinase inhibitory activities abha kathuria, a sarah jalal, a rakesh tiwari, b amir nasrolahi shirazi, b shilpi gupta, a shiv kumar, a keykavous parang, b, sunil k. Coumarins owe their class name to coumarou, the vernacular name of the tonka bean dipteryx odorata willd, fabaceae, from which coumarin, it was isolated in 1820 bruneton, 1999. Pechmann condenation is one of them which is the only method for the synthesis of 3benzyl4methyl coumarins. Chapter 4, section 2 heteroaryl substituted benzoccoumarins department of chemistry, sardar patel university 197 t h harris and j v hay39 have synthesized 1methyl3,7,9 trihydroxy benzoc coumarin alternariol from 3,5,7,9,11,hexaoxotetradecanoic acid by. Synthesis of 8amino7hydroxy4methyl coumarin procedure.
Novel c7substituted coumarins as selective monoamine oxidase. Synthesis of 4substituted coumarins via the palladium. The oxidation of phenols and naphthols by ibx to 1,2quinones is a wellknown reaction. Design, synthesis, and evaluation of in vitro and in vivo. An efficient and practical procedure for the synthesis of. Depending on the substituent pattern of allenes employed, the general synthetic method of 4substituted and 3,4disubstituted 3arylcoumarins.
A number of methods are known in the literature to access coumarin scaffolds. These 4arylcoumarins can also be obtained in good yields 7097% by treatment of 4trifluoromethylsulfonyloxycoumarins 3538. Coumarin and its derivatives represent one of the most active classes of compound possessing a wide spectrum of biological activity 14. The antioxidant activity of new coumarin derivatives. Keeping this in view, useful biological activity of 4substituted coumarins with the. Synthesis of 4substituted coumarins via the palladiumcatalyzed. Design, synthesis, and evaluation of in vitro and in vivo anticancer activity of 4substituted coumarins. Substituted coumarins, docking studies, and dhodh inhibitory activity coumarins are the important class.
Synthesis of some novel 4substituted coumarins having. Palladiumcatalysed coupling of the 4chloro or 4bromo coumarins 14 with arylboronic acids 5 under the suzuki reaction conditions constitutes an efficient access to 4arylcoumarins. In another pechmann condensation synthesis, the ionic liquid 1butyl3methylimidazolium chloroaluminate bmimcl. An efficient and practical procedure for the synthesis of 4substituted coumarins. Temperature dependent green synthesis of 3carboxycoumarins and 3,4unsubstituted coumarins volume. These include perkin,3a pechmann,3b knoevenagel,3c reformatsky3d and wittig3e reactions. H pw o catalyzed efficient synthesis of 4substituted. Furthermore, the 4substituted coumarin linked with benzoyl 3,4dimethoxyaniline through 1,2,3triazole compound 5e displayed the most prominent antiproliferative activities with an ic50 value of 0.
Synthesis and antimicrobial activity of 4substituted 1,2. Jack van schijndel, dennis molendijk, luiz alberto canalle, erik theodorus rump and jan meuldijk affiliation. Facile metalfree synthesis of 3aryl4substituted coumarins from. The order of reactivity of the pseudohalide substituents in the coumarins. Pdf total synthesis of six 3,4unsubstituted coumarins.
Intramolecular cross dehydrogenative coupling of 4. A convenient synthesis of 3behzyl, 3benzyl4substituted. Compound 65 showed potent antiproliferative ability ic 50 values of 747 nm. Rudradas and mereyala hari babu organic chemistry division iii, fine chemical laboratory, indian institute of chemical technology, 500 007hyderabad, india. Dz, substituted at 4position of coumarin were established by their elemental analyses and spectral data table ii. M, about 5000 times stronger than 4hydroxycoumarin ic50 100.