一种高效合成二氢黄酮类化合物的方法
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摘要
提出了一种以2'-羟基查尔酮及其衍生物为原料,以乙醇作溶剂,采用多聚磷酸(PPA)/浓盐酸体系高效合成二氢黄酮类化合物的方法.对化合物a进行了条件优化,考察了反应时间、PPA的物质的量、V(浓盐酸)/V(乙醇)对化合物a产率的影响,得出合成化合物a的最优条件:反应物量为30.0 mg (0.1 mmol)、PPA的物质的量6.0 mmol,V(浓盐酸)/V(乙醇)=1/1,氮气保护下回流反应3 h.采用该方法以产率90.2%～93.6%合成得到5个二氢黄酮类化合物(a～f),所有化合物结构通过MS、~1H NMR、~(13)C NMR进行表征.该方法具有反应条件温和、反应时间短、产率高的优点.
An efficient method for the synthesis of dihydroflavones from 2'-hydroxychalcones with polyphosphoric acid(PPA)/concentrated hydrochloric acid system using ethanol as solvent was reported. Synthesis conditions of compound a were optimized. Effects of reaction time, volume ratio of concentrated hydrochloric acid to ethanol and PPA equivalent on the yield were investigated. The optimum conditions for the synthesis of compound a are obtained: when reactant was 30.0 mg(0.1 mmol), the amount of PPA was 6.0 mmol,V(concentrated hydrochloric acid)/V(ethanol) was 1/1, the reflux reaction time was 3 h under the protection of nitrogen. Five products(a-f) were synthesised in yields of 90.2%～93.6%, and were confirmed by MS, ~1H NMR and ~(13)C NMR. The method has the advantages such as mild reaction conditions, short reaction time and excellent yield.
An efficient method for the synthesis of dihydroflavones from 2'-hydroxychalcones with polyphosphoric acid(PPA)/concentrated hydrochloric acid system using ethanol as solvent was reported. Synthesis conditions of compound a were optimized. Effects of reaction time, volume ratio of concentrated hydrochloric acid to ethanol and PPA equivalent on the yield were investigated. The optimum conditions for the synthesis of compound a are obtained: when reactant was 30.0 mg(0.1 mmol), the amount of PPA was 6.0 mmol,V(concentrated hydrochloric acid)/V(ethanol) was 1/1, the reflux reaction time was 3 h under the protection of nitrogen. Five products(a-f) were synthesised in yields of 90.2%～93.6%, and were confirmed by MS, ~1H NMR and ~(13)C NMR. The method has the advantages such as mild reaction conditions, short reaction time and excellent yield.
引文
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[2]石磊,班树荣,冯秀娥,等.二氢黄酮类衍生物的合成及抗肿瘤活性研究[J].中国药物化学杂志,2010,20(3):176-180.Shi L,Ban S R,Feng X E,et al.Synthesis and antitumor activity of flavanone derivatives[J].Chinese Journal of Medicinal Chemistry,2010,20(3):176-180.
[3]张茵,查晓明,尚靖,等.天然二氢黄酮类化合物研究进展[J].亚太传统医药,2013,9(8):65-70.DOI:10.3969/j.issn.1673-2197.2013.08.031.Zhang Y,Chang X M,Shang J,et al.Recent progress in naturally occurring flavanones[J].Asia-Pacific Traditional Medicine,2013,9(8):65-70.
[4]石磊.二氢黄酮类衍生物的合成及生物活性研究[D].太原:山西医科大学,2010.Shi L.Synthesis and bioactivities of flavanone derivatives[D].Taiyuan:Shanxi Medical University,2010.
[5]刘志平.构棘中黄酮类化合物的分离表征和二氢黄酮肟类、腙类衍生物的合成及活性研究[D].南宁:广西大学,2013.Liu Z P.Isolation,elucidation of flavonoids from Cudrania cochinchinensis and synthesis,cytotoxity of flavanone oximes,flavanone hydrazones[D].Nanning:Guangxi University,2013.
[6]丁薇娜.异戊烯查耳酮和异戊烯二氢黄酮抗糖尿病活性研究[D].天津:天津科技大学,2017.Ding W N.Anti-diabetic activity evaluation of prenylated chalcones and dihydroflavones[D].Tianjin:Tianjin University of Science and Technology,2017.
[7]Havsteen B.Flavonoids,a class of natural products of high pharmacological potency[J].Biochemical Pharmacology,1983,32(7):1 141-1 148.DOI:10.1016/0006-2952(83)90262-9.
[8]Bhattachaqryya A,Chaudhuri A.Synthesis of didymocarpina,a new flavanone isolated from didymocarpus pedicellata[J].Indian Journal of Chemistry Section B-Organic Chemistry Including Medical Chemistry,1988,27(5):462-463.
[9]Singh S,Sharma G D,Verma P K,et al.Association and path-coefficients in Plantago ovata Forsk[J].Indian Journal of Agricultural Sciences,1984,54(7):1 090-1 091.
[10]Drexler M T,Amiridis M D.Kinetic investigation of the heterogeneous synthesis of flavanone over MgO[J].Catalysis Letters,2002,79(14):175-181.
[11]Zheng L,Cortés-Concepción J A,Mustian M,et al.Effect of basic properties of MgO on the heterogeneous synthesis of flavanone[J].Applied Catalysis A General,2006,302(2):232-236.DOI:10.1016/j.apcata.2006.01.007.
[12]Yu H,Li Y,Feng Z,et al.Synthesis,crystal structure and antitumour activity evaluation of 1H-thieno[2,3-c]chromen-4(2H)-one derivatives[J].Journal of Chemical Research,2017,41(1):36-41.DOI:10.3184/174751917X14837116219573.
[13]汪秋安,周强,范华芳.7-羟基黄酮醇和7-羟基黄烷酮及其衍生物的合成[J].合成化学,2007,12(1):50-54.DOI:10.3969/j.issn.1005-1511.2007.01.012.Wang Q A,Zhou Q,Fan H F.Synthesis of 7-hydroxyflavonols and 7-hydroxyflavonones and their derivatives[J].Chinese Journal of Synthetic Chemistry,2007,12(1):50-54.
[14]Li Y,Cai S,He K,et al.Semisynthesis of polymethoxyflavonoids from naringin and hesperidin[J].Journal of Chemical Research,2014,38(5):287-290.DOI:10.3184/174751914X13966139490181.
[15]Dhar D N,Lal J B.Chalcones.Condensation of aromatic aldehydes with sesacetophenone.Ⅱ[J].The Journal of Organic Chemistry,1958,23(8):1 159-1 161.DOI:10.1021/jo01102a021.
[16]Vuppalapati S V N,Xia L K,Edayadulla N,et al.Mild and efficient one-pot synthesis of diverse flavanone derivatives via an organocatalyzed mannich-type reaction[J].Synthesis,2014,46(4):465-474.