Publication: Bazı polihidroksikumarin türevi makrohalkalı eterlerin sentezi
Abstract
Kumarin (2H-1-benzopiran-2-on) birçok bitki hücresinde sentezlenen, parfümeri, diş macunu ve tütün ürünlerinde katkı maddesi olarak kullanılan bir bileşiktir. Kumarin ve hidroksil türevleri, bitkilerde sekonder metabolit olarak sentezlenen izoflavonoid sınıfı bileşiklerdir ve bitkilerde serbest veya glikozidleri halinde bulunurlar. Çok sayıda hidroksil kumarin bileşiği, örneğin; o-dihidroksikumarin türevleri, enzim inhibisyonu, panzehir, karsınojen, antikuagulant ve antibiyotik etki gösterir. Kumarin bileşiğinin 3. pozisyonunda aromatik substituent bulunduran kumarin türevleri; antikuagulan, koroner damarları iyi yönde etkileyen özelliğe sahip bileşiklerdir. Bunlar mükemmel floresans özellik gösterdiklerinden ağartıcı olarak da kullanılabilirler. Bu nedenle kumarin türevlerinin sentezine ilgi devam etmektedir. Daha önce gerçekleştirdiğimiz çalışmaların bir bölümünde farklı o-dihidroksikumarin birimi içeren taç eter türevleri sentezledik ve bunların asetonitril çözeltisinde floresans spektroskopik yöntemi kullanılarak katyon kompleks kararlılıklarını inceledik. Yapılan bu çalışmada ise, 7,8-dihidroksi-3-(3,4-dimetoksifenil)kumarin (1) , 7,8-dihidroksi-3-(3,4-dihidroksifenil)kumarin (3) ve 6,7-dihidroksi-3-(3,4-dihidroksifenil)kumarin (6) türevleri sentezlenmiştir. 7,8-dihidroksi-3-(3,4-dimetoksifenil)kumarin (1) bileşiğinden, 7,8-[12-taç-4]-3-(3,4-dimetoksifenil)kumarin (8), 7,8-[15-taç-5]-3-(3,4-dimetoksifenil)kumarin (9) ve 7,8-[18-taç-6]-3-(3,4-dimetoksifenil)kumarin (10) taç eter türevleri, 7,8-dihidroksi-3-(3,4-dihidroksifenil)kumarin (3) bileşiğinden de 7,8-[12-taç-4]-3-{3,4-[12-taç-4]fenil}kumarin (11) ve 7,8-[15-taç-5]-3-{3,4-[15-taç-5]fenil}kumarin (12) taç eter türevleri sentezlenmiştir. Kumarin taç eterleri; polietilenglikolditosilat ile 7,8-dihidroksi-3-fenilkumarin türevlerinin CH3CN / K2CO3 varlığında çözülmesi, geri soğutucu altında, inert atmosferde, mekanik karıştırıcı ile 70-80oC'de 35 saat karıştırılmasıyla hazırlanmıştır. Saflaştırma işlemi ise, silikajel kolon kromatografisinde yapılmıştır. Yapıları 1H-NMR ve 13C-NMR spektrumları ile karakterize edilmiştir.
THE SYNTHESIS OF SOME CROWN ETHER DERIVATIVES OF POLYHYDROXYCOUMARINS Coumarin (2H-1-benzopyran-2-one) is a naturally-occurring coustituents of many plants wich is added to parfumes, toothpastes and tabacco products. Coumarin and its hydroxy derivatives belong to the isoflovonoid class and are found in the subfamily leguminosae in the free state or as glucosides. Many oxygenated coumarins, e.g., o-dihydroxycoumarin derivatives, show marked biological activity, such as enzym inhibition, hypotoxicity, carcinogenicity, anticoagulant and antibiotic action. Coumarins substituted at 3-position form a very important class of compounds. 3-Phenylcoumarins are known as anticoagulant and coronary constricting agent and a fluorescent brighteners. Therefore, there has been continuing interest in the synthesis of coumarin derivatives on account of their biological activity. We have previously synthesised the various crown ethers with different o-dihydroxycoumarin moieties and reported the cation-complex stabilities using steady state fluoresceuce spectroscopy in acetonitril. In this study, we synthesized 7,8-dihydroxy-3-(3,4-dimethoxyphenyl)coumarin (1), 7,8-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (3) and 6,7-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (6). We also prepared 7,8-[12-crown-4]-3-(3,4-dimethoxyphenyl)coumarin (8), 7,8-[15-crown-5]-3-(3,4-dimethoxyphenyl)coumarin (9) and 7,8-[18-crown-6]-3-(3,4-dimethoxyphenyl)kumarin (10) from 7,8-dihydroxy-3-(3,4-dimethoxyphenyl) coumarin (1) and 7,8-[12-crown-4]-3-{3,4-[12-crown-4]phenyl}coumarin (11) and 7,8-[15-crown-5]-3-{3,4-[15-crown-5]phenyl}coumarin (12) from 7,8-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (3). For the synthesis of coumarin-crown compounds; polyethylenglycolditosylate, 7,8-dihydroxycoumarin derivatives are dissolved in CH3CN / K2CO3, the mixture is heated in the N2 inert atmosphere and stirred mechanically under reflux for 35 hours at 70-80 oC. The purification is performed by using silica gel column chromatography. Finally, the structures of crown compounds are determined based on the results of spectroscopic methods such as 1H-NMR and 13C-NMR.
THE SYNTHESIS OF SOME CROWN ETHER DERIVATIVES OF POLYHYDROXYCOUMARINS Coumarin (2H-1-benzopyran-2-one) is a naturally-occurring coustituents of many plants wich is added to parfumes, toothpastes and tabacco products. Coumarin and its hydroxy derivatives belong to the isoflovonoid class and are found in the subfamily leguminosae in the free state or as glucosides. Many oxygenated coumarins, e.g., o-dihydroxycoumarin derivatives, show marked biological activity, such as enzym inhibition, hypotoxicity, carcinogenicity, anticoagulant and antibiotic action. Coumarins substituted at 3-position form a very important class of compounds. 3-Phenylcoumarins are known as anticoagulant and coronary constricting agent and a fluorescent brighteners. Therefore, there has been continuing interest in the synthesis of coumarin derivatives on account of their biological activity. We have previously synthesised the various crown ethers with different o-dihydroxycoumarin moieties and reported the cation-complex stabilities using steady state fluoresceuce spectroscopy in acetonitril. In this study, we synthesized 7,8-dihydroxy-3-(3,4-dimethoxyphenyl)coumarin (1), 7,8-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (3) and 6,7-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (6). We also prepared 7,8-[12-crown-4]-3-(3,4-dimethoxyphenyl)coumarin (8), 7,8-[15-crown-5]-3-(3,4-dimethoxyphenyl)coumarin (9) and 7,8-[18-crown-6]-3-(3,4-dimethoxyphenyl)kumarin (10) from 7,8-dihydroxy-3-(3,4-dimethoxyphenyl) coumarin (1) and 7,8-[12-crown-4]-3-{3,4-[12-crown-4]phenyl}coumarin (11) and 7,8-[15-crown-5]-3-{3,4-[15-crown-5]phenyl}coumarin (12) from 7,8-dihydroxy-3-(3,4-dihydroxyphenyl)coumarin (3). For the synthesis of coumarin-crown compounds; polyethylenglycolditosylate, 7,8-dihydroxycoumarin derivatives are dissolved in CH3CN / K2CO3, the mixture is heated in the N2 inert atmosphere and stirred mechanically under reflux for 35 hours at 70-80 oC. The purification is performed by using silica gel column chromatography. Finally, the structures of crown compounds are determined based on the results of spectroscopic methods such as 1H-NMR and 13C-NMR.