（R）-和（S）-波密辛A的全合成及细胞毒性
Total Syntheses and Cytotoxicity of (R)- and (S)-Boehmeriasin A.
作者信息
Leighty Matthew W, Georg Gunda I
机构信息
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045 and Department of Medicinal Chemistry and The Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, Minnesota 55414.
出版信息
ACS Med Chem Lett. 2011 Apr 14;2(4):313-315. doi: 10.1021/ml1003074.
Abstract
Both enantiomers of boehmeriasin A were synthesized in seven steps each, using a chiral pool approach. Key steps in the synthesis are a one-flask, two-step protocol to generate the quinolizine core and a C-H functionalization reaction between tetrahydroquinolizinones and an aryltrifluoroborate. The natural product (R)-boehmeriasin A demonstrated potent cytotoxicity against several cancer cell lines, whereas the unnatural (+)-(S)-isomer was significantly less potent.
摘要
采用手性源方法，以七步反应分别合成了波美草素A的两种对映体。合成的关键步骤包括：通过单瓶两步法生成喹嗪核心，以及四氢喹嗪酮与芳基三氟硼酸盐之间的C-H官能化反应。天然产物(R)-波美草素A对几种癌细胞系表现出强大的细胞毒性，而非天然的(+)-(S)-异构体活性则明显较弱。
相似文献
1
Total Syntheses and Cytotoxicity of (R)- and (S)-Boehmeriasin A.（R）-和（S）-波密辛A的全合成及细胞毒性
ACS Med Chem Lett. 2011 Apr 14;2(4):313-315. doi: 10.1021/ml1003074.
2
Asymmetric Total Syntheses of Both Enantiomers of Plymuthipyranone B and Its Unnatural Analogues: Evaluation of -MRSA Activity and Its Chiral Discrimination.普利木噻喃酮B对映体及其非天然类似物的不对称全合成：耐甲氧西林金黄色葡萄球菌活性评估及其手性识别
Pharmaceuticals (Basel). 2021 Sep 19;14(9):938. doi: 10.3390/ph14090938.
3
Total Synthesis of the Antitumor-Antitubercular 2,6'-Bijuglone Natural Product Diospyrin and Its 3,6'-Isomer.抗肿瘤-抗结核 2,6'-双二氢胡桃醌天然产物地奥司林及其 3,6'-异构体的全合成。
J Nat Prod. 2020 Dec 24;83(12):3623-3634. doi: 10.1021/acs.jnatprod.0c00800. Epub 2020 Dec 14.
4
Syntheses and cytotoxicity of (R)- and (S)-7-methoxycryptopleurine.
J Org Chem. 2015 Jan 16;80(2):1284-90. doi: 10.1021/jo502660r. Epub 2015 Jan 7.
5
Induction of G1 arrest and differentiation in MDA-MB-231 breast cancer cell by boehmeriasin A, a novel compound from plant.植物源新型化合物波叶大黄素 A 诱导 MDA-MB-231 乳腺癌细胞 G1 期阻滞及分化
Int J Gynecol Cancer. 2006 Jan-Feb;16(1):165-70. doi: 10.1111/j.1525-1438.2006.00291.x.
6
C-C Bond Cleavage of α-Pinene Derivatives Prepared from Carvone as a General Strategy for Complex Molecule Synthesis.α-蒎烯衍生物的 C-C 键裂解，由香芹酮制备，作为复杂分子合成的一般策略。
Acc Chem Res. 2022 Mar 1;55(5):746-758. doi: 10.1021/acs.accounts.1c00783. Epub 2022 Feb 16.
7
Total Synthesis of γ-Alkylidenebutenolides, Potent Melanogenesis Inhibitors from Thai Medicinal Plant Melodorum fruticosum.γ-烷基丁烯内酯的全合成，来自泰国药用植物 Melodorum fruticosum 的强效黑色素生成抑制剂。
J Org Chem. 2018 Aug 3;83(15):8250-8264. doi: 10.1021/acs.joc.8b00986. Epub 2018 Jul 17.
8
Synthesis of new derivatives of boehmeriasin A and their biological evaluation in liver cancer.新型 Boehmeriasin A 衍生物的合成及其在肝癌中的生物学评价。
Eur J Med Chem. 2019 Mar 15;166:243-255. doi: 10.1016/j.ejmech.2019.01.056. Epub 2019 Jan 24.
9
Enantioselective and Synergetic Toxicity of Axial Chiral Herbicide Propisochlor to SP2/0 Myeloma Cells.轴手性除草剂丙酯草醚对 SP2/0 骨髓瘤细胞的对映选择性和协同毒性。
J Agric Food Chem. 2015 Sep 16;63(36):7914-20. doi: 10.1021/acs.jafc.5b03027. Epub 2015 Sep 2.
10
A Concise Enantioselective Synthesis and Cytotoxic Evaluation of the Anticancer Rotenoid Deguelin Enabled by a Tandem Knoevenagel/Conjugate Addition/Decarboxylation Sequence.通过串联Knoevenagel/共轭加成/脱羧序列实现的抗癌类柠檬苦素鱼藤素的简洁对映选择性合成及细胞毒性评估
Chem Sci. 2013 Aug;4(8):3304-3309. doi: 10.1039/C3SC50424G.
引用本文的文献
1
On the application of 3d metals for C-H activation toward bioactive compounds: The key step for the synthesis of silver bullets.3D金属在用于生物活性化合物的C-H活化方面的应用：合成“银弹”的关键步骤。
Beilstein J Org Chem. 2021 Jul 30;17:1849-1938. doi: 10.3762/bjoc.17.126. eCollection 2021.
2
Sequential C-H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor.连续 C-H 芳基化和对映选择性氢化可实现理想的非对映选择性进入 11β-HSD-1 抑制剂的茚并哌啶核心。
J Am Chem Soc. 2016 Nov 30;138(47):15473-15481. doi: 10.1021/jacs.6b09764. Epub 2016 Nov 17.
3
Synthesis of Enantioenriched 2-Alkyl Piperidine Derivatives through Asymmetric Reduction of Pyridinium Salts.通过吡啶盐的不对称还原合成对映体富集的2-烷基哌啶衍生物
Org Lett. 2016 Oct 7;18(19):4920-4923. doi: 10.1021/acs.orglett.6b02401. Epub 2016 Sep 23.
4
Regioselective C5-alkylation and C5-methylcarbamate formation of 2,3-dihydro-4-pyridones and C3-alkylation and C3-methylcarbamate formation of 4-(pyrrolidin-1-yl)furan-2(5)-one.2,3-二氢-4-吡啶酮的区域选择性C5-烷基化和C5-甲基氨基甲酸酯形成以及4-(吡咯烷-1-基)呋喃-2(5)-酮的C3-烷基化和C3-甲基氨基甲酸酯形成。
Tetrahedron Lett. 2015 Oct 21;56(43):5874-5877. doi: 10.1016/j.tetlet.2015.09.004.
5
Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid: Proposed Structure of a Castoreum Component.一种睡莲生物碱的对映体特异性合成及生物学研究：海狸香成分的推测结构
European J Org Chem. 2014 Jun 1;2014(18):3777-3783. doi: 10.1002/ejoc.201402232.
6
Preparation of dibenzo[e,g]isoindol-1-ones via Scholl-type oxidative cyclization reactions.通过肖尔型氧化环化反应制备二苯并[e,g]异吲哚-1-酮
J Org Chem. 2014 Sep 5;79(17):8049-58. doi: 10.1021/jo501185f. Epub 2014 Aug 25.
7
Biomimetic Aerobic C-H Olefination of Cyclic Enaminones at Room Temperature: Development toward the Synthesis of 1,3,5-Trisubstituted Benzenes.室温下环状烯胺酮的仿生需氧C-H烯基化反应：迈向1,3,5-三取代苯合成的进展
Adv Synth Catal. 2014 Apr 14;356(6):1359-1369. doi: 10.1002/adsc.201300904.
8
Enantioselective synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from β-substituted β-hydroxyaminoaldehydes.β-取代β-羟氨基醛的对映选择性合成 3,4-二氢-1,2-噁嗪-5(2H)-酮和 2,3-二氢吡啶-4(1H)-酮。
J Org Chem. 2014 Feb 7;79(3):984-92. doi: 10.1021/jo402445r. Epub 2014 Jan 13.
9
Boron-Heck reaction of cyclic enaminones: regioselective direct arylation via oxidative palladium(II) catalysis.环状烯胺酮的硼-赫克反应：通过氧化钯（II）催化的区域选择性直接芳基化反应。
Org Lett. 2014 Mar 21;16(6):1574-7. doi: 10.1021/ol500105d. Epub 2014 Mar 3.
10
Palladium-catalyzed direct C-H arylation of cyclic enaminones with aryl iodides.钯催化的环状烯胺酮与芳基碘化物的直接 C-H 芳基化反应。
J Org Chem. 2013 Jun 21;78(12):6163-9. doi: 10.1021/jo400830t. Epub 2013 Jun 10.
本文引用的文献
1
Synthesis of tylocrebrine and related phenanthroindolizidines by VOF3-mediated oxidative aryl-alkene coupling.通过 VOF3 介导的氧化芳基-烯烃偶联反应合成泰洛菌素和相关的菲并吲哚里嗪。
Org Lett. 2011 Jan 21;13(2):196-9. doi: 10.1021/ol1023954. Epub 2010 Dec 14.
2
Synthesis of 6- and 7-membered cyclic enaminones: scope and mechanism.合成 6- 和 7-元环烯胺酮：范围和机理。
J Org Chem. 2010 Oct 15;75(20):6793-805. doi: 10.1021/jo100907u.
3
Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine.阿林吲哚里西啶生物碱 (+)-异波林碱和 (+)-安托啡的全合成。
J Org Chem. 2010 Sep 3;75(17):6019-22. doi: 10.1021/jo101051w.
4
Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy.菲并吲哚里西啶和菲并喹诺里西啶：用于抗癌治疗的有前景的生物碱。
Curr Bioact Compd. 2009 Mar 1;5(1):2-19. doi: 10.2174/157340709787580928.
5
Microwave-assisted Suzuki-Miyaura couplings on α-iodoenaminones.α-碘代烯胺酮上的微波辅助铃木-宫浦偶联反应
Tetrahedron Lett. 2007 Dec 10;48(50):8811-8814. doi: 10.1016/j.tetlet.2007.10.078.
6
Palladium(II)-catalyzed direct arylation of enaminones using organotrifluoroborates.钯（II）催化的烯胺酮与有机三氟硼酸盐的直接芳基化反应。
J Am Chem Soc. 2008 Mar 26;130(12):3708-9. doi: 10.1021/ja710221c. Epub 2008 Mar 6.
7
Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones.6,7-二芳基-2,3,8,8a-四氢中氮茚-5(1H)-酮的合成、体外和体内细胞毒性
Bioorg Med Chem Lett. 2007 Aug 15;17(16):4703-7. doi: 10.1016/j.bmcl.2007.05.103. Epub 2007 Jun 13.
8
Total syntheses of the tylophora alkaloids cryptopleurine, (-)-antofine, (-)-tylophorine, and (-)-ficuseptine C.娃儿藤生物碱隐脉娃儿藤碱、（-）-安托非宁、（-）-娃儿藤碱和（-）-榕藤碱C的全合成。
Chemistry. 2006 Sep 25;12(28):7398-410. doi: 10.1002/chem.200600592.
9
Amino acid-derived enaminones: a study in ring formation providing valuable asymmetric synthons.氨基酸衍生的烯胺酮：关于环形成的研究，提供有价值的不对称合成子。
J Am Chem Soc. 2006 Jul 12;128(27):8702-3. doi: 10.1021/ja0609046.
10
Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents.抗肿瘤药物251：新型抗肿瘤药物菲基娃儿藤碱衍生物（PBTs）的合成、细胞毒性评价及构效关系研究
Bioorg Med Chem. 2006 Oct 1;14(19):6560-9. doi: 10.1016/j.bmc.2006.06.009. Epub 2006 Jun 30.
Zotero 插件