脱氢枞基伯胺衍生物的合成及其抗癌活性研究

doi:10.3969/j.issn.0253-2417.2018.06.016

林产化学与工业 ›› 2018, Vol. 38 ›› Issue (6): 117-123.doi: 10.3969/j.issn.0253-2417.2018.06.016

脱氢枞基伯胺衍生物的合成及其抗癌活性研究

齐志文^1,2, 王成章¹, 蒋建新²

1. 中国林业科学研究院林产化学工业研究所;生物质化学利用国家工程实验室;国家林业局林产化学工程重点开放性实验室;江苏省生物质能源与材料重点实验室, 江苏南京 210042;
2. 北京林业大学材料科学与技术学院, 北京 100083

收稿日期:2018-05-16 出版日期:2018-12-25 发布日期:2018-12-27
通讯作者: 王成章,研究员,博士,博士生导师,主要从事天然产物研究;E-mail:wangczlhs@sina.com。 E-mail:wangczlhs@sina.com
作者简介:齐志文(1989-),男,湖北襄阳人,博士生,从事天然产物化学研究;E-mail:angelkissgod@163.com
基金资助:
国家自然科学基金资助项目（31570564）；江苏省生物质能源与材料重点实验室基本科研业务费项目（JSBEM-S-201509）

Synthesis and Anticancer Activity of Dehydroabietyl Primary Amine Derivatives

QI Zhiwen^1,2, WANG Chengzhang¹, JIANG Jianxin²

1. Institute of Chemical Industry of Forest Products, CAF;National Engineering Lab. for Biomass Chemical Utilization;Key and open Lab. of Forest Chemical Engineering, SFA;Key Lab. of Biomass Energy and Material, Jiangsu Province, Nanjing 210042, China;
2. College of Materials Science and Technology, Beijing Forestry University, Beijing 100083, China

Received:2018-05-16 Online:2018-12-25 Published:2018-12-27

摘要/Abstract

摘要： 以左旋海松酸（0.3 mmol）为原料、三乙胺（TEA）为碱、1-（3-二甲胺基丙基）-3-乙基碳二亚胺盐酸盐（EDCI）为脱水剂、1H-苯并三唑-1-基氧三吡咯烷基六氟磷酸盐/4-二甲氨基吡啶（n（PyBOP）：n（DMAP）=0.03 mmol：0.01 mmol）为催化剂、乙腈（MeCN）为溶剂，简单、高效地合成了脱氢枞基伯胺衍生物：脱氢枞酰胺甲酸（1），脱氢枞酰胺乙酸（2），脱氢枞酰胺丙酸（3），脱氢枞酰胺丁酸（4），并对其结构进行了表征，其中化合物3产率可达78%。经伯胺酰胺化后的化合物3对人胃癌MKN-45细胞株具有较高的增殖抑制活性，IC₅₀值为31.26 μmol/L。

关键词: 左旋海松酸, 脱氢枞酸, 羧基, 位阻, 伯胺, 酰胺化

Abstract: The primary amine derivatives of dehydroabietic acid:dehydroabietic amide formic acid (1), dehydroabietic amide acetic acid (2), dehydroabietic amide propionic acid (3) and dehydroabietic amide butyric acid (4) were synthesized by a simple and efficient one-pot method with levopimaric acid (0.3 mmol) as raw material, triethylamine (TEA) as base, 1-(3-dimethylamino propyl)-3-ethyl carbodiimide hydrochloride (EDCI) as dehydrant, 1H benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate/4-dimethylamino pyridine (n(PyBOP):n(DMAP)=0.03 mmol:0.01 mmol) as catalyst and acetonitrile as solvent. The yield of the compound 3 were up to 78%. The compound 3 modified by primary amine had a high proliferation inhibitory activity toward human gastric cancer MKN-45 cell line with the IC₅₀ of 31.26 μmol/L.

Key words: levopimaric acid, dehydroabietic acid, carboxyl group, steric resistance, primary amine, amidation

中图分类号:

TQ35

齐志文, 王成章, 蒋建新. 脱氢枞基伯胺衍生物的合成及其抗癌活性研究[J]. 林产化学与工业, 2018, 38(6): 117-123.

QI Zhiwen, WANG Chengzhang, JIANG Jianxin. Synthesis and Anticancer Activity of Dehydroabietyl Primary Amine Derivatives[J]. Chemistry and Industry of Forest Products, 2018, 38(6): 117-123.

参考文献

[1] HELFENSTEIN A,VAHERMO M,NAWROT D A,et al. Antibacterial profiling of abietane-type diterpenoids[J]. Bioorganic & Medicinal Chemistry,2017,25(1):132-137.
[2] VAFINA G F,UZBEKOV A R,ZARUBAEV V V,et al. Search for antiviral agents among quinopimaric acid scaffold derivatives[J]. Chemistry of Natural Compounds,2015,51(1):103-107.
[3] TRETYAKOVA E V,SMIRNOVA I E,KAZAKOVA O B,et al. Synthesis and anticancer activity of quinopimaric and maleopimaric acids' derivatives[J]. Bioorganic & Medicinal Chemistry,2014,22(22):6481-6489.
[4] TRETYAKOVA E V,SMIRNOVA I E,SALIMOVA E V,et al. Synthesis and antiviral activity of maleopimaric and quinopimaric acids' derivatives[J]. Bioorganic & Medicinal Chemistry,2015,23(20):6543-6550.
[5] 孙曙光. 左旋海松酸分离方法的改进[J]. 林产化工通讯,1992,26(3):20-21. SUN S G. Levopimaric acid purification optimization[J]. Journal of Chemical Indurstry of Forest Products,1992,26(3):20-21.
[6] HUANG X C,HUANG R Z,LIAO Z X,et al. Synthesis and pharmacological evaluation of dehydroabietic acid thiourea derivatives containing bisphosphonate moiety as an inducer of apoptosis[J]. European Journal of Medicinal Chemistry,2016,108:381-391.
[7] XING Y H,ZHANG W,SONG J J,et al. Anticancer effects of a novel class rosin-derivatives with different mechanisms[J]. Bioorganic & Medicinal Chemistry Letter,2013,23(13):3868-3872.
[8] WASOWSKI C,MARDER M. Central nervous system activities of two diterpenes isolated from Aloysia virgata[J]. Phytomedicine,2011,18(5):393-401.
[9] BERDY J. Thoughts and facts about antibiotics:Where we are now and where we are heading[J]. The Journal of Antibiotics,2012,65(8):385-395.
[10] SHAN W G,WANG H G,CHEN Y,et al. Synthesis of 3-and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities[J]. Bioorganic & Medicinal Chemistry Letter,2017,27(15):3450-3453.
[11] SOMMERWERK S,HELLER L,KERZIG C,et al. Rhodamine B conjugates of triterpenoic acids are cytotoxic mitocans even at nanomolar concentrations[J]. European Journal of Medicinal Chemistry,2017,127:1-9.
[12] VILUMS M,ZWEEMER A J,BARMARE F,et al. When structure-affinity relationships meet structure-kinetics relationships:3-((Inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as CCR2 antagonists[J]. European Journal of Medicinal Chemistry,2015,93:121-134.
[13] JIANG F,WANG H J,BAO Q C,et al. Optimization and biological evaluation of celastrol derivatives as hsp90-cdc37 interaction disruptors with improved druglike properties[J]. Bioorganic & Medicinal Chemistry,2016,24(21):5431-5439.
[14] WANG Z M,LI J P,ZENG X D,et al. Synthesis and pharmacological evaluation of novel benzenesulfonamide derivatives as potential anticonvulsant agents[J]. Molecules,2015,20(9):17585-17600.
[15] SHI H,FANG L C,TAN C H,et al. Total syntheses of drimane-type sesquiterpenoids enabled by a gold-catalyzed tandem reaction[J]. Journal of the American Chemical Society,2011,133(38):14944-14947.
[16] AIHARA Y,CHATANI N. Nickel-catalyzed reaction of C-H bonds in amides with I₂:Ortho-iodination via the cleavage of C(sp2)-H bonds and oxidative cyclization to β-lactams via the cleavage of C(sp3)-H bonds[J]. ACS Catalysis,2016,6(7):4323-4329.
[17] GOU Q,YANG Y W,LIU Z N,et al. Intermolecular amination of unactivated C(sp3)-H bonds with cyclic alkylamines:Formation of C(sp3)-N bonds through copper/oxygen-mediated C(sp3)-H/N-H activation[J]. Chemistry,2016,22(45):16057-16061.
[18] SHANG R,ILIES L,MATSUMOTO A,et al. β-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation[J]. Journal of the American Chemical Society,2013,135(16):6030-6032.
[19] LUO F X,XU X,WANG D,et al. Cu-Catalyzed alkynylation of unactivated C(sp(3))-X bonds with terminal alkynes through directing strategy[J]. Organic Letters,2016,18(9):2040-2043.
[20] YE X H,PETERSEN J L,SHI X D. Nickel-catalyzed directed sulfenylation of sp(2) and sp(3) C-H bonds[J]. Chemical Communications,2015,51(37):7863-7866.
[21] WANG Z,NI J Z,KUNINOBU Y,et al. Copper-catalyzed intramolecular C(sp(3))-H and C(sp(2))-H amidation by oxidative cyclization[J]. Angewandte Chemie (International ed. in English),2014,53(13):3496-3499.
[22] UM S J,PARK M S,PARK S H,et al. Synthesis of new glycyrrhetinic acid (GA) derivatives and their effects on tyrosinase activity[J]. Bioorganic & Medicinal Chemistry,2003,11(24):5345-5352.
[23] STRAGIES R,OSTERKAMP F,ZISCHINSKY G,et al. Design and synthesis of a new class of selective integrin α5β1 antagonists[J]. Journal of Medicinal Chemistry,2007,50(16):3786-3794.
[24] RODRIGUEZ A L,TAMRAZI A,COLLINS M L,et al. Design,synthesis,and in vitro biological evaluation of small molecule inhibitors of estrogen receptor alpha coactivator binding[J]. Journal of Medicinal Chemistry,2003,47(3):600-611.
[25] MARCHAND P,PUGET A,BAUT G L,et al. Palladium(Ⅱ)-catalyzed heterocyclisation of 8-arylethynyl-1,2,3,4-tetrahydroquinolines:A facile route to 2-aryl-5,6-dihydro-4H-pyrrolo[3,2,1-ij] quinoline derivatives[J]. Tetrahedron,2005,61(16):4035-4041.

脱氢枞基伯胺衍生物的合成及其抗癌活性研究

Synthesis and Anticancer Activity of Dehydroabietyl Primary Amine Derivatives

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