[go: up one dir, main page]

CN112745288A - β-烷氧基醇二苯并呫吨类化合物及其应用 - Google Patents

β-烷氧基醇二苯并呫吨类化合物及其应用 Download PDF

Info

Publication number
CN112745288A
CN112745288A CN202011594679.3A CN202011594679A CN112745288A CN 112745288 A CN112745288 A CN 112745288A CN 202011594679 A CN202011594679 A CN 202011594679A CN 112745288 A CN112745288 A CN 112745288A
Authority
CN
China
Prior art keywords
compound
dibenzo
alcohol
solution
dibenzoxanthene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202011594679.3A
Other languages
English (en)
Other versions
CN112745288B (zh
Inventor
陈泳
潘文龙
李洁
李正全
罗枝伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute Of Testing And Analysis Guangdong Academy Of Sciences Guangzhou Analysis And Testing Center China
Original Assignee
Institute Of Testing And Analysis Guangdong Academy Of Sciences Guangzhou Analysis And Testing Center China
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institute Of Testing And Analysis Guangdong Academy Of Sciences Guangzhou Analysis And Testing Center China filed Critical Institute Of Testing And Analysis Guangdong Academy Of Sciences Guangzhou Analysis And Testing Center China
Priority to CN202011594679.3A priority Critical patent/CN112745288B/zh
Publication of CN112745288A publication Critical patent/CN112745288A/zh
Application granted granted Critical
Publication of CN112745288B publication Critical patent/CN112745288B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了式(Ⅰ)或式(Ⅱ)所示的β‑烷氧基醇二苯并呫吨类化合物。本发明提出的β‑烷氧基醇二苯并呫吨类化合物具有较高的抗肿瘤活性，在制备抗肿瘤药物中具有较好的前景。
Figure DDA0002869989370000011
其中：R为H、CH3或CH2CH3；R1为H、COOCH3或CONH(CH2)2OH，R2为H、COOCH3、CONH(CH2)2OH或CONH2。

Description

β-烷氧基醇二苯并呫吨类化合物及其应用
技术领域：
本发明涉及具有抗癌活性的化合物及其应用领域，具体涉及一种β-烷氧基醇二苯并呫吨类化合物及其应用。
背景技术：
恶性肿瘤是一种严重威胁人类健康的常见病和多发病，因恶性肿瘤引起的死亡率在所有疾病中占第二位，仅次于心脑血管疾病。肿瘤的治疗，尤其是恶性肿瘤的治疗在很大程度上以化学治疗为主。苯并呫吨化合物属于二苯并吡喃或氧杂蒽类芳杂环化合物，研究表明该类化合物具有抗病毒、抗细菌、抗炎等广泛的药理作用。因此，近年来越来越多的化学和药物研究者对苯并呫吨化合物类的进行广泛研究。王秀珍等人报道合成二苯并呫吨化合物并发现该类化合物具有抗肿瘤活性以及诱导肿瘤细胞发生凋亡。说明二苯并[a,kl]呫吨化合物的抗肿瘤生物活性比较显著，具有良好的抗肿瘤药物开发与应用前景，但是目前该化合物还存在很多问题，水溶性和低毒性不够完善，因此需要解决此类问题使化合物能更好的开发应用。
发明内容：
本发明的目的是提供一种β-烷氧基醇二苯并呫吨类化合物及其应用，对二苯并[a,kl]呫吨 2，3位的双键环氧化化合物进行开环生成本发明提出的β-烷氧基醇二苯并呫吨类化合物，该化合物对肿瘤细胞具有比较显著的低毒。
本发明是通过以下技术方案予以实现的：
式(Ⅰ)或式(Ⅱ)所示的β-烷氧基醇二苯并呫吨类化合物：
Figure BDA0002869989360000021
其中：R为H、CH3或CH2CH3；R1为H、COOCH3或CONH(CH2)2OH，R2为H、COOCH3、 CONH(CH2)2OH或CONH2。本发明还保护所述的β-烷氧基醇二苯并呫吨类化合物的制备方法，包括以下步骤：将二苯并[a,kl]呫吨化合物溶解于溶剂中得到二苯并[a,kl]呫吨化合物溶液，所述的二苯并[a,kl]呫吨化合物溶液的摩尔浓度为0.06mol/L，加入FeCl3溶液，二苯并[a, kl]呫吨化合物与FeCl3的摩尔比为20:1，在35℃-40℃下搅拌反应3-47h，TLC跟踪至二苯并 [a,kl]呫吨化合物消失，加入HCl溶液和适量的水，乙酸乙酯萃取，有机相用无水硫酸钠干燥，旋干，所得粗产品进行硅胶柱层析分离和洗脱，得到β-烷氧基醇二苯并呫吨类化合物。
上述反应所涉及的反应方程式如下：
Figure BDA0002869989360000022
其中：R为H、CH3或CH2CH3；R1为H、COOCH3或CONH(CH2)2OH，R2为H、COOCH3、 CONH(CH2)2OH或CONH2，反应中所用的溶剂为醇溶液或DMSO与水体积比为1:1的混合溶液。
本发明还保护所述的β-烷氧基醇二苯并呫吨类化合物制备抗肿瘤药物的应用。特别是β- 烷氧基醇二苯并呫吨类化合物制备抗肿瘤药物的应用在制备抗肝癌药物、抗胃癌药物或抗肺癌药物中的应用。
本发明还保护所述的β-烷氧基醇二苯并呫吨类化合物及其药学上可接受的盐组合成的药学上可接受的药物组合物或制剂在制备抗肿瘤药物的应用。一种药物组合物，包含至少一种式I或式Ⅱ所示的β-烷氧基醇二苯并呫吨类化合物作为活性成分，单独或结合一种或几种药学上可接受的、惰性的、无毒的赋形剂或载体。
本发明的有益效果是：
(1)本发明的β-烷氧基醇类二苯并呫吨化合物具有较高的抗肿瘤活性，在制备抗肿瘤药物中具有较好的前景。
(2)β-烷氧基醇类二苯并呫吨化合物的制备方法简单，合成过程中使用醇和FeCl3作为溶剂和催化剂，催化剂简单易得且简化了操作步骤，催化效果突出，反应条件温和，后处理简单，产率较高。
具体实施方式：
以下是对本发明的进一步说明，而不是对本发明的限制。除特别说明，本发明中的实验材料和试剂均为本技术领域常规市购产品或自制产品。
反应方程式如下：
Figure BDA0002869989360000031
其中：R为H、CH3或CH2CH3；R1为H、COOCH3或CONH(CH2)2OH，R2为H、COOCH3、 CONH(CH2)2OH或CONH2，反应中所用的溶剂为醇溶液或DMSO与水体积比为1:1的混合溶液。
β-烷氧基醇类二苯并呫吨化合物的制备步骤如下：将1mmol原料溶解于15mL甲醇或者乙醇，再加入0.1mol/L的FeCl3溶液，加入量为0.5mL，在35℃-40℃下搅拌反应3-47h。TLC 跟踪至原料消失，加入少量质量分数为5％的HCl溶液和适量的水，乙酸乙酯萃取三次，有机相用无水硫酸钠干燥，旋干，所得粗产品进行硅胶柱层析分离，以石油醚和乙酸乙酯的混合物为洗脱剂，得到产物。
实施例1：
原料中R为CH3，R1为H，R2为H，溶剂为甲醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的1a1和1a2。
Figure BDA0002869989360000041
1-氧代-2-甲氧基-3-羟基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(1a1)
灰白色固体,Yield,52.97％,m.p.128.7-130.7℃,1H-NMR(500MHz,Acetone-d6)δ:8.16(d, J＝5.0Hz,1H),8.06(d,J＝5.0Hz,1H),8.04(d,J＝5.0Hz,1H),7.73(d,J＝15.0Hz,1H),7.60(d, J＝5.0Hz,1H),7.57(d,J＝5.0Hz,1H),7.53(d,J＝5.0Hz,1H),7.52(d,J＝5.0Hz,1H),7.43(d, J＝10.0Hz,1H),5.82(dd,J＝10.0Hz,1H),4.76(d,J＝5.0Hz,1H),4.52(d,J＝5.0Hz,1H),3.79(s, 3H),2.87(s,3H).13C-NMR(125MHz,Acetone-d6)δ:205.2,151.3,150.9,140.1,132.0,131.9, 131.1,131.0,128.6,126.7,126.4,124.6,120.4,117.2,115.3,112.3,107.7,78.7,77.7,69.5,57.3, 49.8.IR(KBr,cm-1)ν:3386,2930,2826,2361,1738,1582,1452,1349,1270,1089,1045,808, 773,605.HRMS calcd forC22H18NaO5[M+Na]+385.10519,found[M+Na]+385.10464.
Figure BDA0002869989360000051
1-氧代-2-羟基-3-甲氧基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(1a2)
灰白色固体,Yield,25.57％,m.p.154.7-156.2℃,1H-NMR(500MHz,DMSO-d6)δ:8.18(d, J＝5.0Hz,1H),8.15(d,J＝10.0Hz,1H),8.05(d,J＝5.0Hz,1H),7.67(d,J＝15.0Hz,1H),7.59(d, J＝5.0Hz,1H),7.58(d,J＝5.0Hz,1H),7.56(d,J＝5.0Hz,1H),7.52(d,J＝15.0Hz,1H),7.34(d, J＝5.0Hz,1H),5.80(d,J＝5.0Hz,1H),5.44(d,J＝10.0Hz,1H),4.00(dd,J＝15.0Hz,1H),3.89(s, 3H),2.96(s,3H).13C-NMR(125MHz,DMSO-d6)δ:202.9,151.2,150.8,140.6,132.5,131.7, 131.7,131.1,129.1,127.0,126.9,125.1,120.6,117.7,115.6,111.9,107.9,78.8,77.5,69.4,57.8, 50.6.IR(KBr,cm-1)ν:3461,3062,2929,2821,2362,1736,1452,1284,1267,1041,1023,814, 808,749.HRMS calcd forC22H18NaO5[M+Na]+385.10519,found[M+Na]+385.10464。
实施例2：
原料中R为CH3，R1为COOCH3，R2为COOCH3，溶剂为甲醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的1b1和 1b2。
Figure BDA0002869989360000061
1-氧代-2-甲氧基-3-羟基-5,11-二甲氧羰基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(1b1)
黄色固体,Yield,34.35％,m.p.119.2-121.7℃,1H-NMR(500MHz,DMSO-d6)δ:8.71(s, 1H),8.36(d,J＝10.0Hz,1H),8.00(d,J＝10.0Hz,1H),7.96(s,1H),7.91(d,J＝10.0Hz,1H),7.87 (d,J＝5.0Hz,1H),7.61(d,J＝10.0Hz,1H),5.93(d,J＝10.0Hz,1H),5.64(dd,J＝10.0Hz,1H),4.70 (d,J＝5.0Hz,1H),3.94(s,6H),3.61(s,3H),2.66(s,3H).13C-NMR(125MHz,DMSO-d6)δ:202.8, 166.6,165.5,152.9,150.8,138.7,134.2,133.9,133.0,131.7,130.6,127.3,126.8,126.5,126.1, 121.4,118.7,116.9,108.1,88.4,77.5,74.7.IR(KBr,cm-1)ν:3448,2951,2850,2361,1724,1628, 1429,1291,1221,1201,1100,889,770.HRMS calcd for C26H22NaO9[M+Na]+501.11615,found [M+Na]+501.11560.
Figure BDA0002869989360000062
1-氧代-2-羟基-3-甲氧基-5,11-二甲氧羰基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(1b2)
黄色固体,Yield,34.35％,m.p.132.6-133.8℃,1H-NMR(500MHz,DMSO-d6)δ:8.69(s, 1H),8.35(d,J＝10.0Hz,1H),8.09(d,J＝15.0Hz,1H),7.98(d,J＝10.0Hz,1H),7.95(s,1H),7.89 (d,J＝5.0Hz,1H),7.68(d,J＝5.0Hz,1H),5.61(d,J＝5.0Hz,1H),5.59(d,J＝5.0Hz,1H),5.23(t, J＝10.0Hz,1H),3.92(s,6H),3.67(s,3H),2.76(s,3H).13C-NMR(125MHz,DMSO-d6)δ:204.2, 167.3,162.7,152.4,151.7,145.2,136.8,134.3,133.4,130.1,127.5,126.7,126.5,125.9,121.3, 119.3,116.6,109.3,86.3,76.5,75.4.IR(KBr,cm-1)ν:3457,2876,2439,1678,1580,1471,1397, 1201,1099,1040,986,817,756,664.HRMScalcd for C26H22NaO9[M+Na]+501.11615,found [M+Na]+501.11560.
实施例3：
原料中R为CH3，R1为H，R2为CONH2，溶剂为甲醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的1c1和1c2。
Figure BDA0002869989360000071
1-氧代-2-甲氧基-3-羟基-11-甲酰胺基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (1c1)
红褐色固体,Yield,50.54％,m.p.133.7-135.3℃,1H-NMR(500MHz,DMSO-d6)δ:8.51(s, 1H),8.16(d,J＝10.0Hz,1H),8.13(d,J＝10.0Hz,1H),7.91(d,J＝10.0Hz,1H),7.81(d,J＝10.0Hz, 1H),7.63(d,J＝15.0Hz,1H),7.52(d,J＝10.0Hz,1H),7.47(s,1H),7.40(s,1H),7.38(d,J＝5.0Hz, 1H),5.83(d,J＝10.0Hz,1H),5.59(dd,J＝10.0Hz,1H),4.58(d,J＝5.0Hz,1H),3.54(s,3H),2.62 (s,3H).13C-NMR(125MHz,DMSO-d6)δ:203.3,168.2,152.3,150.8,137.7,133.4,132.9,131.8, 130.9,129.1,126.7,125.4,118.4,117.0,116.4,108.3,89.0,77.7,75.5,74.7,60.5,57.0,50.5.IR (KBr,cm-1)ν:3356,2923,2850,2823,1739,1663,1930,1456,1394,1276,1092,1045,811,786, 578.HRMS calcd forC23H19NNaO6[M+Na]+428.11101,found[M+Na]+428.11046.
Figure BDA0002869989360000081
1-氧代-2-羟基-3-甲氧基-11-甲酰胺基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (1c2)
黄色固体,Yield,23.13％,m.p.137.3-139.6℃,1H-NMR(500MHz,DMSO-d6)δ:8.52(s, 1H),8.16(d,J＝10.0Hz,1H),8.13(d,J＝5.0Hz,1H),7.98(d,J＝10.0Hz,1H),7.92(d,J＝10.0Hz, 1H),7.59(d,J＝15.0Hz,1H),7.52(d,J＝5.0Hz,1H),7.48(s,1H),7.42(d,J＝10.0Hz,1H),7.32(d, J＝15.0Hz,1H),5.57(d,J＝10.0Hz,1H),5.49(d,J＝5.0Hz,1H),5.22(dd,J＝10.0Hz,1H),3.64(s, 3H),2.74(s,3H).13C-NMR(125MHz,DMSO-d6)δ:202.8,168.2,150.7,140.6,133.5,131.8, 130.9,130.3,129.0,126.8,125.4,120.8,118.5,115.7,111.8,108.0,78.6,77.3,69.3,57.8,50.6, 30.5,29.3,27.0.IR(KBr,cm-1)ν:3355,2924,2853,2361,1735,1663,1456,1396,1348,1264, 1045,813,793,753,705,577.HRMScalcd for C23H19NNaO6[M+Na]+428.11101,found[M+Na]+ 428.11046.
实施例4：
原料中R为CH3，R1为H，R2为COOCH3，溶剂为甲醇溶液，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的1d1和1d2。
Figure BDA0002869989360000091
1-氧代-2-甲氧基-3-羟基-11-甲氧羰基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (1d1)
黄白色固体,Yield,41.99％,m.p.157.8-159.4℃,1H-NMR(500MHz,DMSO-d6)δ:8.70(s, 1H),8.33(d,J＝10.0Hz,1H),7.98(d,J＝10.0Hz,1H),7.91(d,J＝10.0Hz,1H),7.65(d,J＝15.0Hz, 1H),7.57(d,J＝10.0Hz,1H),7.43(d,J＝5.0Hz,1H),7.41(d,J＝5.0Hz,1H),5.84(d,J＝5.0Hz, 1H),5.59(dd,J＝5.0Hz 5.0Hz,1H),4.60(s,1H),3.92(s,3H),3.56(s,3H),2.64(s,3H).13C-NMR (125MHz,DMSO-d6)δ:203.2,198.4,166.6,152.9,151.0,150.7,140.0,137.7,134.1,132.2,131.9, 127.6,126.9,120.7,118.9,117.0,108.5,107.7,81.4,78.1,77.6,74.7,57.1,50.6.IR(KBr,cm-1)ν: 3507,2987,2947,2820,1734,1629,1398,1291,1266,1095,1072,944,813,775,627.HRMS calcd for C24H20NaO7[M+Na]+443.11067,found[M+Na]+443.11012.
Figure BDA0002869989360000092
1-氧代-2-羟基-3-甲氧基-11-甲氧羰基-13c-甲氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(1d2)
黄白色固体,Yield,12.2％,m.p.182.2-184.4℃,1H-NMR(300MHz,DMSO-d6)δ:8.68(s, 1H),8.32(d,J＝9.0Hz,1H),8.05(d,J＝9.0Hz,1H),7.96(d,J＝9.0Hz,1H),7.61(d,J＝6.0Hz,1H), 7.57(d,J＝3.0Hz,1H),7.43(d,J＝9.0Hz,1H),7.32(d,J＝9.0Hz,1H),5.57(d,J＝9.0Hz,1H),5.53 (d,J＝9.0Hz,1H),5.21(dd,J＝12.0Hz,1H),3.92(s,3H),3.64(s,3H),2.74(s,3H).13C-NMR(125 MHz,DMSO-d6)δ:203.2,176.0,152.9,150.7,134.6,133.9,131.9,131.5,130.4,127.4,126.1, 125.5,125.9,120.9,118.9,115.7,111.7,108.2,106.9,78.6,77.3,69.3,57.8,52.7,50.7.IR(KBr, cm-1)ν:3421,2952,2840,2359,1743,1710,1629,1449,1293,1260,1123,1104,977,810,799, 565.HRMS calcd for C24H20NaO7[M+Na]+443.11067,found[M+Na]+443.11012.
实施例5：
原料中R为CH3，R1为CONH(CH2)2OH，R2为CONH(CH2)2OH，溶剂为甲醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的1e1和1e2。
Figure BDA0002869989360000101
1-氧代-2-甲氧基-3-羟基-11-(N-羟乙基甲酰胺基)-13c-甲氧基-1,2,3,13c-四氢-二苯并[a, kl]-呫吨(1e1)
黄白色固体,Yield,43.21％,m.p.130.0-131.1℃,1H-NMR(500MHz,DMSO-d6)δ:8.50(s, 1H),8.15(d,J＝10.0Hz,1H),7.96(s,1H),7.95(d,J＝5.0Hz,1H),7.92(t,J＝5.0Hz,1H),7.63(d, J＝10.0Hz,1H),7.48(d,J＝10.0Hz,1H),7.42(d,J＝10.0Hz,1H),7.35(d,J＝5.0Hz,1H),5.69(d, J＝5.0Hz,1H),4.46(d,J＝5.0Hz,1H),4.60(d,J＝5.0Hz,1H),3.86(s,1H),3.73(t,J＝10.0Hz,2H), 3.66(s,3H),3.57-3.54(q,J＝15.0Hz,2H),2.75(s,3H).13C-NMR(125MHz,DMSO-d6)δ:202.6, 166.8,152.3,151.0,137.5,132.8,131.6,131.1,130.4,128.0,126.8,126.3,124.6,120.3,118.0, 117.9,115.9,89.3,77.3,76.2,74.9,61.0,56.5,49.7,42.7.IR(KBr,cm-1)ν:3355,2933,2823,2360, 1740,1541,1455,1267,1071,1054,810,750,624.HRMS calcd for C25H23NNaO7[M+Na]+ 472.13722,found[M+Na]+472.13667.
Figure BDA0002869989360000111
1-氧代-2-羟基-3-甲氧基-11-(N-羟乙基甲酰胺基)-13c-甲氧基-1,2,3,13c-四氢-二苯并[a, kl]-呫吨(1e2)
白色固体,Yield,11.16％,m.p.156.2-158.1℃,1H-NMR(500MHz,DMSO-d6)δ:8.60(q, J＝15.0Hz,1H),8.48(s,1H),8.17(d,J＝10.0Hz,1H),7.99(d,J＝10.0Hz,1H),7.90(dd,J＝5.0Hz 5.0Hz,1H),7.59(q,J＝15.0Hz,1H),7.52(d,J＝10.0Hz,1H),7.42(d,J＝10.0Hz,1H),7.30(d, J＝10.0Hz,1H),5.57(d,J＝10.0Hz,1H),5.49(d,J＝10.0Hz,1H),5.21(t,J＝10.0Hz,1H), 4.80-4.77(dd,J＝5.0Hz 5.0Hz,1H),3.64(s,3H),3.57-3.54(q,J＝15.0Hz,2H),3.36-3.34(q, J＝10.0Hz,2H),2.73(s,3H).13C-NMR(125MHz,DMSO-d6)δ:201.7,166.5,153.5,152.3,138.7, 132.6,131.8,130.9,130.2,128.8,126.9,126.4,126.2,123.9,118.2,117.4,115.4,92.1,78.8,76.6, 72.2,65.4,56.5,47.3,40.4.HRMScalcd for C25H23NNaO7[M+Na]+472.13722,found [M+Na]+472.13667.
实施例6：
原料中R为CH2CH3，R1为H，R2为H，溶剂为乙醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的2a1和2a2。
Figure BDA0002869989360000121
1-氧代-2-乙氧基-3-羟基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(2a1)
灰白色固体,Yield,46.22％,m.p.118.6-119.7℃,1H-NMR(500MHz,DMSO-d6)δ:8.38(d, J＝9.0Hz,1H),8.28(d,J＝9.0Hz,1H),8.16(d,J＝9.0Hz,1H),7.91(d,J＝16.0Hz,1H),7.82(d, J＝8.5Hz,1H),7.80(d,J＝8.5Hz,1H),7.75(d,J＝9.0Hz,1H),7.67(d,J＝6.5Hz,1H),7.65(d, J＝9.5Hz,1H),6.09(d,J＝8.0Hz,1H),5.89(dd,J＝2.0Hz2.0Hz,1H),4.95(d,J＝2.0Hz,1H), 4.16-4.12(m,J＝23.5Hz,1H),4.09-4.05(m,J＝16.5Hz,1H),3.18-3.15(q,J＝15.5Hz,1H), 2.95-2.92(q,J＝15.5Hz,1H),1.56-1.53(t,J＝15.0Hz,3H),1.15-1.12(t,J＝15.0Hz,3H).13C-NMR (125MHz,DMSO-d6)δ:206.0,153.3,153.1,140.4,134.7,134.0,133.8,133.5,131.5,129.3,129.2, 128.8,127.5,120.2,120.0,118.6,111.4,90.1,79.6,77.6,66.9,61.1,18.3,17.7.IR(KBr,cm-1)ν: 2975,2925,1732,1474,1307,1268,1086,1049,1011,815,798,607.HRMS calcd for C24H22KO5 [M+K]+429.11043,found[M+K]+429.10988.
Figure BDA0002869989360000131
1-氧代-2-羟基-3-乙氧基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(2a2)
灰白色固体,Yield,23.24％,m.p.153.5-155.7℃,1H-NMR(500MHz,DMSO-d6)δ:8.05(d, J＝5.0Hz,1H),7.98(d,J＝10.0Hz,1H),7.95(d,J＝5.0Hz,1H),7.55(d,J＝15.0Hz,1H),7.48(d, J＝5.0Hz,1H),7.46(d,J＝5.0Hz,1H),7.42(d,J＝5.0Hz,1H),7.40(d,J＝10.0Hz,1H),7.25(d, J＝10.0Hz,1H),5.70(d,J＝5.0Hz,1H),5.37(d,J＝5.0Hz,1H),5.13-5.11(dd,J＝5.0Hz 5.0Hz, 1H),3.99-3.96(q,J＝15.0Hz,1H),3.73-3.70(q,J＝15.0Hz,1H),2.94-2.91(q,J＝15.0Hz,1H), 2.75-2.72(q,J＝15.0Hz,1H),1.33-1.30(t,J＝15.0Hz,3H),0.88-0.85(t,J＝15.0Hz,3H).13C-NMR (125MHz,DMSO-d6)δ:205.1,153.3,152.9,141.7,134.8,133.9,133.5,131.5,129.3,129.8,127.5, 123.0,120.1,121.7,119.7,118.0,111.1,80.7,78.3,72.2,67.8,61.5,18.1,18.0.IR(KBr,cm-1)ν:3484,2974,2924,2854,1740,1475,1459,1364,1265,1249,1145,1065,1005,809,743.HRMScalcd for C24H22KO5[M+K]+429.11043,found[M+K]+429.10988.
实施例7：
原料中R为CH2CH3，R1为COOCH3，R2为COOCH3，溶剂为乙醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的2b1和2b2。
Figure BDA0002869989360000141
1-氧代-2-乙氧基-3-羟基-5,11-二甲氧羰基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(2b1)
黄白色固体,Yield,35.48％,m.p.81.3-83.7℃,1H-NMR(500MHz,DMSO-d6)δ:8.63(s, 1H),8.27(d,J＝10.0Hz,1H),7.91(s,1H),7.88(d,J＝10.0Hz,1H),7.76(d,J＝5.0Hz,1H),7.51(d, J＝10.0Hz,1H),5.82(d,J＝10.0Hz,1H),5.54-5.52(dd,J＝5.0Hz 5.0Hz,1H),4.67(s,1H), 4.15-4.13(q,J＝10.0Hz,1H),3.78-3.76(q,J＝10.0Hz,1H),2.77-2.74(q,J＝15.0Hz,1H), 2.66-2.63(q,J＝15.0Hz,1H),1.20-1.17(t,J＝15.0Hz,3H),0.78-0.76(t,J＝10.0Hz,3H).13C-NMR (125MHz,DMSO-d6)δ:203.1,166.6,165.5,152.5,152.5,144.6,134.0,132.9,131.6,130.5,127.2, 126.7,126.0,122.0,118.7,116.8,108.9,87.1,76.9,75.1,64.9,59.2,53.2,52.8,19.9,15.2.IR(KBr, cm-1)ν:3448,2924,2368,1725,1629,1473,1429,1290,1221,1100,770,754.HRMS calcd for C28H26KO9[M+K]+545.12139,found[M+K]+545.12084.
Figure BDA0002869989360000142
1-氧代-2-羟基-3-乙氧基-5,11-二甲氧羰基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (2b2)
黄白色固体,Yield,12.98％,m.p.102.2-104.1℃,1H-NMR(500MHz,DMSO-d6)δ:8.32(s, 1H),8.27(d,J＝5.0Hz,1H),8.07(s,1H),7.99(d,J＝15.0Hz,1H),7.97(d,J＝10.0Hz,1H),7.56(d, J＝10.0Hz,1H),5.37(d,J＝5.0Hz,1H),5.32(d,J＝5.0Hz,1H),4.48-4.47(q,J＝5.0Hz,1H), 4.23-4.21(dd,J＝5.0Hz 5.0Hz,1H),4.08-4.06(q,J＝10.0Hz,1H),2.98-2.94(q,J＝20.0Hz,1H), 2.79-2.76(q,J＝15.0Hz,1H),1.37-1.34(t,J＝15.0Hz,3H),0.91-0.88(t,J＝15.0Hz,3H).13C-NMR (125MHz,DMSO-d6)δ:202.1,166.2,165.0,152.9,152.6,146.3,133.4,131.8,131.3,130.2,128.2, 127.0,126.2,123.4,117.1,116.2,107.9,85.4,72.4,70.2,63.8,59.2,53.5,51.7,21.1.IR(KBr,cm-1) ν:3436,2895,1678,1567,1466,1322,1285,1222,988,771,738,590.HRMS calcd for C28H26KO9[M+K]+545.12139,found[M+K]+545.12084.
实施例8：
原料中R为CH2CH3，R1为H，R2为CONH2，溶剂为乙醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的2c1和2c2。
Figure BDA0002869989360000151
1-氧代-2-乙氧基-3-羟基-11-甲酰胺基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (2c1)
黄白色固体,Yield,41.14％,m.p.109.4-111.3℃,1H-NMR(300MHz,DMSO-d6)δ:8.52(s, 1H),8.21(d,J＝9.0Hz,1H),8.16(d,J＝9.0Hz,1H),7.94(d,J＝9.0Hz,1H),7.90(d,J＝6.0Hz,1H), 7.60(d,J＝6.0Hz,1H),7.52(d,J＝6.0Hz,1H),7.49(d,J＝6.0Hz,1H),7.39(d,J＝9.0Hz,1H),6.78 (d,J＝6.0Hz,1H),5.83(d,J＝9.0Hz,1H),5.60-5.58(dd,J＝3.0Hz 3.0Hz,1H),4.66(d,J＝3.0Hz, 1H),3.87-3.85(q,J＝6.0Hz,1H),3.79-3.76(q,J＝9.0Hz,1H),2.76-2.73(q,J＝9.0Hz,1H), 2.52-2.50(q,J＝6.0Hz,1H),1.27-1.23(t,J＝12.0Hz,3H),0.86-0.82(t,J＝12.0Hz,3H).13C-NMR (125MHz,DMSO-d6)δ:203.5,168.2,150.6,138.0,133.3,133.0,131.7,130.8,130.3,129.1,126.7, 125.3,118.4,117.6,116.3,109.1,87.6,77.1,75.2,64.6,58.8,15.4,15.3.IR(KBr,cm-1)ν:3357, 3198,2975,2925,2854,1664,1584,1472,1392,1348,1265,1049,817,791,770.HRMS calcd forC25H23NNaO6[M+Na]+456.14231,found[M+Na]+456.14176.
Figure BDA0002869989360000161
1-氧代-2-羟基-3-乙氧基-11-甲酰胺基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (2c2)
黄白色固体,Yield,8.53％,m.p.122.9-125.7℃,1H-NMR(500MHz,DMSO-d6)δ:8.65(s, 1H),8.52(d,J＝10.0Hz,1H),8.25(s,1H),8.23(s,1H),7.93(d,J＝10.0Hz,1H),7.87(d,J＝10.0 Hz,1H),7.84(d,J＝10.0Hz,1H),7.62(d,J＝10.0Hz,1H),7.60(d,J＝10.0Hz,1H),7.11(d,J＝5.0 Hz,1H),5.32(d,J＝9.0Hz,1H),4.18-4.16(dd,J＝5.0Hz 5.0Hz,1H),4.14(d,J＝5.0Hz,1H), 4.09-4.06(m,J＝15.0Hz,2H),2.02-1.96(m,J＝30.0Hz,2H),1.08-1.05(t,J＝15.0Hz,3H), 0.86-0.84(t,J＝10.0Hz,3H).13C-NMR(125MHz,DMSO-d6)δ:202.2,179.8,168.6,157.6,155.7, 140.9,138.9,134.7,132.4,132.0,130.1,130.0,129.3,128.4,126.0,121.5,119.1,81.5,61.5,35.6, 29.6,27.0,25.6,22.6,14.4.HRMScalcd for C25H23NNaO6[M+Na]+456.14231,found [M+Na]+456.14176.
实施例9：
原料中R为CH2CH3，R1为H，R2为COOCH3，溶剂为乙醇，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的2d1和2d2。
Figure BDA0002869989360000171
1-氧代-2-乙氧基-3-羟基-11-甲氧羰基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (2d1)
黄白色固体,Yield,30.71％,m.p.141.3-143.6℃,1H-NMR(500MHz,DMSO-d6)δ:8.67(s, 1H),8.29(d,J＝10.0Hz,1H),7.96(d,J＝5.0Hz,1H),7.94(d,J＝5.0Hz,1H),7.61(d,J＝15.0Hz, 1H),7.53(d,J＝5.0Hz,1H),7.38(d,J＝15.0Hz,1H).5.80(d,J＝5.0Hz,1H),5.56-5.54(dd,J＝5.0 Hz 5.0Hz,1H),4.64(s,1H),3.90(s,3H),3.79-3.76(q,J＝15.0Hz,1H),3.68-3.65(q,J＝15.0Hz, 1H),2.88-2.85(q,J＝15.0Hz,1H),2.64-2.61(q,J＝15.0Hz,1H),1.24-1.22(t,J＝5.0Hz,3H), 0.83-0.82(t,J＝5.0Hz,3H).13C-NMR(125MHz,DMSO-d6)δ:198.5,166.7,152.3,150.7,140.4, 139.1,135.3,134.8,132.1,131.5,130.3,129.0,125.4,119.5,118.8,115.9,112.8,108.5,79.6,75.1, 67.9,61.6,59.0,52.9,16.0,14.5.IR(KBr,cm-1)ν:3427,2975,2926,2826,1275,1630,1467,1291,1197,1115,1050,820,802,782,723,633.HRMS calcd for C26H24KO7[M+K]+487.11591,found [M+K]+487.11536.
Figure BDA0002869989360000181
1-氧代-2-羟基-3-乙氧基-11-甲氧羰基-13c-乙氧基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨 (2d2)
黄白色固体,Yield,17.02％,m.p.170.1-172.4℃,1H-NMR(500MHz,DMSO-d6)δ:8.27(s,1H), 8.08(d,J＝20.0Hz,1H),7.96(d,J＝15.0Hz,1H),7.71(d,J＝15.0Hz,1H),7.58(d,J＝10.0Hz,1H), 7.54(d,J＝15.0Hz,1H),7.42(d,J＝5.0Hz,1H).7.28(d,J＝10.0Hz,1H),5.69(d,J＝5.0Hz,1H), 5.55(d,J＝5.0Hz,1H),5.13-5.10(t,J＝15.0Hz,1H),3.98-3.96(q,J＝10.0Hz,1H),3.90(s,1H), 3.75-3.73(q,J＝10.0Hz,1H),2.96-2.92(q,J＝20.0Hz,1H),2.76-2.72(q,J＝20.0Hz,1H), 1.33-1.30(t,J＝15.0Hz,3H),0.89-0.85(t,J＝20.0Hz,3H).13C-NMR(75MHz,DMSO-d6)δ:199.7, 166.7,152.6,150.4,140.9,134.7,133.8,131.7,131.5,130.3,127.5,126.0,125.8,118.9,115.7, 108.9,78.1,75.8,69.7,65.3,59.3,52.7,15.7,15.6.IR(KBr,cm-1)ν:3495,2948,2869,1742,1718, 1467,1303,1264,1105,1069,1048,976,822,751.HRMS calcd for C26H24KO7[M+K]+487.11591,found[M+K]+487.11536.
实施例10：
原料中R为H，R1为H，R2为H，溶剂为DMSO与水体积比为1:1的混合溶液15mL，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的3a。
Figure BDA0002869989360000191
1-氧代-2-羟基-3-羟基-13c-羟基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(3a)
白色固体,Yield,52.36％,m.p.102.5-104.8℃,1H-NMR(500MHz,DMSO-d6)δ:7.99(d, J＝10.0Hz,1H),7.93(d,J＝10.0Hz,1H),7.82(d,J＝10.0Hz,1H),7.51(d,J＝15.0Hz,1H),7.47(d, J＝10.0Hz,1H),7.44(d,J＝10.0Hz,1H),7.39(d,J＝10.0Hz,1H),7.34(d,J＝5.0Hz,1H),7.24(d, J＝10.0Hz,1H),7.21(s,1H),6.17(d,J＝5.0Hz,1H),5.56-5.54(dd,J＝10.0Hz,1H),5.50(d, J＝10.0Hz,1H),4.72-4.70(dd,J＝10.0Hz,1H).13C-NMR(125MHz,DMSO-d6)δ:205.4,149.0, 149.0,141.3,131.6,131.3,131.1,130.8,128.9,127.7,126.4,125.0,124.7,121.4,117.8,115.6, 113.5,80.1,77.4,71.0,60.3,21.3,14.6.IR(KBr,cm-1)ν:3456,2923,2852,1736,1584,1457, 1269,1230,1053,1007,981,815,749.HRMS calcd for C20H14KO5[M+K]+373.04783，found [M+K]+373.04728.
实施例11：
原料中R为H，R1为H，R2为COOCH3，溶剂为DMSO与水体积比为1:1的混合溶液 15ml，反应温度为40℃，加入的催化剂为0.1mol/L的FeCl3溶液，加入量为0.5mL，原料经开环反应生成下述的3b。
Figure BDA0002869989360000201
1-氧代-2-羟基-3-羟基-11-甲氧羰基-13c-羟基-1,2,3,13c-四氢-二苯并[a,kl]-呫吨(3b)
红褐色固体,Yield,30.77％,m.p.148.4-151.6℃,1H-NMR(500MHz,DMSO-d6)δ:8.76(s, 1H),8.34(d,J＝5.0Hz,1H),8.06(d,J＝10.0Hz,1H),8.00(d,J＝10.0Hz,1H),7.66(d,J＝10.0Hz, 1H),7.62(d,J＝10.0Hz,1H),7.53(s,1H),7.49(d,J＝10.0Hz,1H),7.39(d,J＝10.0Hz,1H),6.48 (d,J＝5.0Hz,1H),5.78(d,J＝5.0Hz,1H),5.70-5.68(dd,J＝10.0Hz,1H),4.83-4.81(dd,J＝10.0Hz, 1H),4.03(s,1H).13C-NMR(75MHz,DMSO-d6)δ:205.2,166.7,150.8,148.9,141.3,134.5,132.8, 131.5,131.0,130.3,128.1,125.7,125.4,125.3,121.2,119.0,115.8,113.7,80.0,77.4,70.9,60.3, 52.7.IR(KBr,cm-1)ν:3357,2922,2852,1728,1689,1655,1469,1290,1261,990,822,790,669, 624.HRMS calcdfor C22H16KO7[M+K]+431.05331,found[M+K]+431.05276.
实施例1-11对取代环氧化二苯并[a,kl]呫吨化合物的开环条件进行了探讨，发现以 FeCl3为催化剂，取代环氧化二苯并[a,kl]呫吨化合物可以在醇溶剂中发生开环反应，生成β- 烷氧基醇二苯并呫吨类化合物。实验反应结果及参数列表如表1所示。
表1
Figure BDA0002869989360000202
Figure BDA0002869989360000211
实施例12：β-烷氧基醇二苯并呫吨类化合物抗肿瘤活性试验
采用MTT实验对实施例1-11得到的部分β-烷氧基醇二苯并呫吨类化合物体外抑制肿瘤细胞生长进行检测。
取代二苯并[a,kl]呫吨化合物：我们采用MTT实验对化合物体外抑制肿瘤细胞生长进行检测，分别选取人肝癌细胞株HepG2、人肝癌细胞株BEL-7402、人胃癌细胞株SGC-7901、人肺癌细胞株A549分别进行了筛选。具体方法为：将处于对数生长期的各肿瘤细胞株按8× 104个/孔的细胞量接种至96孔板中，放置于培养箱中孵育24h，更换培养液后加入浓度梯度的各药物，使药物终浓度为10-6-10-4mol/L，每组设置3个平行复孔，且设置培养液空白对照孔。然后在培养箱中孵育48h，各孔都加入不含血清的培养基90μL和浓度为5mg/mL的MTT溶液10μL，然后在培养箱中培养4h，加入100μL DMSO微量振荡器中震荡15min后，采用酶标仪490nm处测定吸光度值。按下式计算细胞成活率：
Figure BDA0002869989360000212
Figure BDA0002869989360000213
将各组药物的浓度与所对应的细胞成活率绘制出细胞生长曲线，从曲线图中读出当细胞成活率为50％时所对应的化合物浓度，该浓度即为IC50值。结果参见表2。
表2部分β-烷氧基醇类二苯并呫吨的体外细胞毒性(IC50，μmol/L)
Figure BDA0002869989360000221
由表2可以看到，测试化合物对四种肿瘤细胞均显示较高的毒性；特别是化合物2a2，对 SGC-7901的毒性为5.3μmol/L，2d1对Bel-7402和A549的光毒性分别为9.3μmol/L和6.3μmol/L。以上结果表明，β-烷氧基醇二苯并呫吨类化合物是潜在的抗肿瘤药物。
上列详细说明是针对本发明可行实施例的具体说明，该实施例并非用以限制本发明的专利范围，凡未脱离本发明所为的等效实施或变更，均应包含于本案的专利保护范围中。

Claims (7)

1.式(Ⅰ)或式(Ⅱ)所示的β-烷氧基醇二苯并呫吨类化合物：
Figure FDA0002869989350000011
其中：R为H、CH3或CH2CH3；R1为H、COOCH3或CONH(CH2)2OH，R2为H、COOCH3、CONH(CH2)2OH或CONH2。
2.权利要求1所述的β-烷氧基醇二苯并呫吨类化合物的制备方法，其特征在于，包括以下步骤：将二苯并[a,kl]呫吨化合物溶解于溶剂中得到二苯并[a,kl]呫吨化合物溶液，所述的二苯并[a,kl]呫吨化合物溶液的摩尔浓度为0.06mol/L，加入FeCl3溶液，二苯并[a,kl]呫吨化合物与FeCl3的摩尔比为20:1，在35℃-40℃下搅拌反应3-47h，TLC跟踪至二苯并[a,kl]呫吨化合物消失，加入HCl溶液和适量的水，乙酸乙酯萃取，有机相用无水硫酸钠干燥，旋干，所得粗产品进行硅胶柱层析分离和洗脱，得到β-烷氧基醇二苯并呫吨类化合物。
3.根据权利要求2所述的β-烷氧基醇二苯并呫吨类化合物的制备方法，其特征在于，所述的溶剂为醇溶液或DMSO与水体积比为1:1的混合溶液。
4.根据权利要求3所述的β-烷氧基醇二苯并呫吨类化合物的制备方法，其特征在于，所述的醇溶液为乙醇溶液。
5.权利要求1所述的β-烷氧基醇二苯并呫吨类化合物在制备抗肿瘤药物中的应用。
6.根据权利要求5所述的β-烷氧基醇二苯并呫吨类化合物在制备抗肿瘤药物中的应用，其特征在于，β-烷氧基醇二苯并呫吨类化合物制备抗肿瘤药物的应用在制备抗肝癌药物、抗胃癌药物或抗肺癌药物中的应用。
7.含有权利要求1所述的β-烷氧基醇二苯并呫吨类化合物及其药学上可接受的盐组合成的药学上可接受的药物组合物或制剂在制备抗肿瘤药物的应用。
CN202011594679.3A 2020-12-29 2020-12-29 β-烷氧基醇二苯并呫吨类化合物及其应用 Active CN112745288B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011594679.3A CN112745288B (zh) 2020-12-29 2020-12-29 β-烷氧基醇二苯并呫吨类化合物及其应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011594679.3A CN112745288B (zh) 2020-12-29 2020-12-29 β-烷氧基醇二苯并呫吨类化合物及其应用

Publications (2)

Publication Number Publication Date
CN112745288A true CN112745288A (zh) 2021-05-04
CN112745288B CN112745288B (zh) 2022-09-16

Family

ID=75647724

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011594679.3A Active CN112745288B (zh) 2020-12-29 2020-12-29 β-烷氧基醇二苯并呫吨类化合物及其应用

Country Status (1)

Country Link
CN (1) CN112745288B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116102530A (zh) * 2023-02-03 2023-05-12 广东省科学院测试分析研究所(中国广州分析测试中心) 氰基取代二苯并呫吨化合物及其应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108727329A (zh) * 2018-06-12 2018-11-02 广东省测试分析研究所（中国广州分析测试中心） N-羟乙基甲酰胺基取代二苯并呫吨及其应用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108727329A (zh) * 2018-06-12 2018-11-02 广东省测试分析研究所（中国广州分析测试中心） N-羟乙基甲酰胺基取代二苯并呫吨及其应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JI-YAN PANG ET AL.: "13c-Methoxy-1,2,3,13c-tetrahydrodibenzo[a,kl]-xanthan-1-one", 《ACTA CRYSTALLOGRAPHICA SECTION E》 *
YU-HENG LIU ET AL.: "Amberlyst-15 as a new and reusable catalyst for regioselective ring-opening reactions of epoxides to β-alkoxy alcohols", 《JOURNAL OF MOLECULAR CATALYSIS A: CHEMICAL》 *
陈之朋 等: "二苯并呫吨类化合物的环氧化反应研究", 《有机化学》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116102530A (zh) * 2023-02-03 2023-05-12 广东省科学院测试分析研究所(中国广州分析测试中心) 氰基取代二苯并呫吨化合物及其应用
CN116102530B (zh) * 2023-02-03 2024-06-11 广东省科学院测试分析研究所(中国广州分析测试中心) 氰基取代二苯并呫吨化合物及其应用

Also Published As

Publication number Publication date
CN112745288B (zh) 2022-09-16

Similar Documents

Publication Publication Date Title
WO2007082475A1 (fr) Nouveau composé diterpène ent-kaurène et ses dérivés, leur préparation et leur utilisation
CN102397269A (zh) 查尔酮类化合物在制备抗炎药物中的应用
CN109897021B (zh) 葡萄藤戊素衍生物、其制法以及药物组合物与用途
CN114315855A (zh) 莪术醇类衍生物、制备方法及其在制备抗炎药物中的应用
CN101463058B (zh) 羊毛脂烷型三萜化合物海莲酸、其衍生物及其制备方法和用途
CN112745288B (zh) β-烷氧基醇二苯并呫吨类化合物及其应用
Zhou et al. Design, synthesis and anti-tumor activities of carbamate derivatives of cinobufagin
Min et al. Glycosylation of ent-kaurene derivatives and an evaluation of their cytotoxic activities
CN114656438A (zh) 一种5,7-二羟基-2,2-二甲基-6-乙酰基-色满及其合成方法和应用
CN108752404B (zh) 一种三氮唑糖修饰的小檗碱盐衍生物及其制备方法和用途
CN115073406B (zh) 一种桉烷型倍半萜内酯类tba衍生物及其用途
CN108929353B (zh) 一种鼠李糖或核糖修饰的小檗碱盐衍生物及其制备方法和用途
CN115057839B (zh) 一种桉烷型倍半萜烯内酯化合物及其制备和用途
CN113501773B (zh) 羧酸类药物的β-酮亚砜衍生物及其制备方法和应用
CN101570524A (zh) 取代的穿心莲内酯衍生物及其制备方法和用途
CN114957169A (zh) 一种紫杉醇棕榈酸酯的制备方法
CN104327034B (zh) 5位和7位酯基儿茶素分子选择性制备方法
US20090054516A1 (en) Composition for treating cancer cells and synthetic method for the same
CN108358879B (zh) 灯盏乙素苷元醚类衍生物及其制备方法与应用
CN116925021A (zh) 去氢木香烃内酯烷基化衍生物及其盐、药物组合物及其用途
CN109704925B (zh) 一种吉马酮衍生物及其制备方法与应用
CN115246802B (zh) 一类葡萄素衍生物、其制法及药物组合物与用途
EP1731522A1 (en) Process for producing flavone c glycoside derivatives
CN112010791B (zh) 含苯磺酰胺结构单元的新型苯乙酸紫草宁酯类衍生物及其合成方法和应用
CN111960995A (zh) 含类肉桂酸骨架紫草宁羧酸酯类衍生物及其合成方法和应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant