Novel Synthesis of Thioflavones and Their Pyridyl Analogs from 2-Mercaptobenzoic(nicotinic) Acid

IF 0.3 Q4 CHEMISTRY, MULTIDISCIPLINARY
Jae In Lee
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引用次数: 1

Abstract

Thioflavones have the skeleton of a thiochromen-4-one ring, which serves as a building block for biologically active molecules. Thioflavones have drawn much attention because of their various pharmacological activities such as antimalarial, antiviral, and antimicrobial activity. They also inhibit the proliferation of tumor cells while thioflavonoids, such as 3’,4’-dimethoxythioflavone, relax vascular contraction by activation of the EGF receptor. Several types of synthetic reactions for thioflavones and their heterocyclic analogs have been described in the literature. Among them, a tandem reaction using 2’-substituted chalcones and ynones allows for the efficient synthesis of thioflavones and their heterocyclic analogs. Three types of 2’-substituted chalcones, which were prepared from the condensation of arylaldehydes and 2’-substituted acetophenones, were converted to thioflavones by the following methods (Scheme 1(a)): (i) Treatment of 3-aryl-1-[2-(t-butylsulfanyl)phenyl]prop-2-en-1-ones with 3 equiv. iodine and NaHCO3 at reflux in EtCN. 7 (ii) Cyclization of 2’-tosyloxychalcones with 5 equiv. sulfur in the presence of Et3N in DMSO at 80 °C. This method produced thioflavones together with (Z)-thioaurones as byproducts. (iii) Cu-catalyzed cyclization of 2’-iodo(bromo)chalcones using 2 equiv. potassium ethyl xanthogenate followed by the sequential oxidation of thioflavanone intermediates using H2SO4 in DMSO at 80 °C. The coupling of 2-(methylthio)benzoyl chlorides and arylacetylenes with 2.5 equiv. AlCl3 in CH2Cl2, followed by the addition of chloride, afforded the 2’-(methylthio)β-chlorochalcone intermediates. These intermediates underwent sequential 1,4-addition of sulfur atom and demethylation by chloride anion to yield the thioflavones (Scheme 1(b)). Similarly, sequential addition of NaSH-elimination-SNAr reaction to 2’-halo-β-chlorochalcones, in the presence of 2 equiv. Cs2CO3 in DMSO at 140 °C, also afforded the thioflavones (Scheme 1(b)). On the other hand, the 1,4-addition of 1-(2-methoxyphenyl)-3-phenylprop-2-yn-1-ones with sodium sulfide nonahydrate produced 3-mercapto-1-(2-methoxyphenyl)-3-
以2-巯基苯甲酸(烟酸)为原料合成硫代黄酮及其吡啶基类似物的新方法
硫代黄酮类化合物具有硫铬-4- 1环的骨架,它是生物活性分子的组成部分。硫代黄酮类化合物因其具有抗疟、抗病毒、抗菌等多种药理活性而受到广泛关注。它们还抑制肿瘤细胞的增殖,而硫黄酮,如3 ',4 ' -二甲氧基硫黄酮,通过激活EGF受体来放松血管收缩。文献中描述了几种类型的硫黄酮及其杂环类似物的合成反应。其中,利用2′取代查尔酮和炔酮的串联反应可以有效地合成硫黄酮及其杂环类似物。由芳醛和2′取代苯乙酮缩合而成的3种2′取代查尔酮,通过以下方法(方案1(a))转化为硫黄酮:(i)在EtCN中用3等碘和NaHCO3回流处理3-芳基-1-[2-(t-丁基磺酸基)苯基]2-烯-1-酮。7 (ii)在80℃的DMSO中,在Et3N存在下,2′-甲氧基查尔酮与5个等硫环化。该方法与副产物(Z)-硫酮一起制备了硫黄酮。(iii)用2等量乙基黄原酸钾铜催化2′-碘(溴)查尔酮环化,然后用H2SO4在DMSO中连续氧化硫黄酮中间体,温度为80℃。2-(甲基硫代)苯甲酰氯和芳基乙炔与2.5等量的AlCl3在CH2Cl2中偶联,然后加入氯,得到2 ' -(甲基硫代)β-氯查尔酮中间体。这些中间体依次经过硫原子的1,4加成和氯阴离子的去甲基化,得到硫黄酮(方案1(b))。同样,在140°C的DMSO中,在2等量的Cs2CO3存在下,纳什-消除- snar反应顺序加入到2 ' -halo-β-氯查尔酮中,也得到了硫黄酮(方案1(b))。另一方面,1-(2-甲氧基苯基)-3-苯基丙-2-炔-1- 1与非水合硫化钠的1,4加成反应生成3-巯基-1-(2-甲氧基苯基)-3-
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来源期刊
CiteScore
0.60
自引率
40.00%
发文量
0
期刊介绍: The Journal of Korean Chemical Society has been published since 1949 as the official research journal of the Korean Chemical Society. It is now published bimonthly. The Journal of Korean Chemical Society accepts creative research papers in all fields of pure and applied chemistry including chemical education written by in Korean and English. - Physical Chemistry - Inorganic Chemistry - Analytical Chemistry - Organic Chemistry - Biochemistry - Macromolecular Chemistry - Industrial Chemistry - Materials Chemistry - Chemical Education
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