4-C-甲基-DAB和4-C-甲基-LAB（对映体烷基支链吡咯烷亚氨基糖）是特异性强效α-葡萄糖苷酶抑制剂；以丙酮作为唯一的保护基团。
4-C-Me-DAB and 4-C-Me-LAB - enantiomeric alkyl-branched pyrrolidine iminosugars - are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group.
作者信息
da Cruz Filipa P, Newberry Scott, Jenkinson Sarah F, Wormald Mark R, Butters Terry D, Alonzi Dominic S, Nakagawa Shinpei, Becq Frederic, Norez Caroline, Nash Robert J, Kato Atsushi, Fleet George W J
机构信息
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
出版信息
Tetrahedron Lett. 2011 Jan 12;52(2):219-223. doi: 10.1016/j.tetlet.2010.10.173.
Abstract
The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pK(a) of the salt around 8.4] is discussed and illustrates the need for care in analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K(i) 0.89 μM, IC(50) 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase K(i) 0.95 μM, IC(50) 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB, and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.
摘要
从l-赤藓糖内酯合成4-C-甲基-DAB[1,4-二脱氧-1,4-亚氨基-4-C-甲基-D-阿拉伯糖醇]以及从d-赤藓糖内酯合成4-C-甲基-LAB仅需一个丙酮叉保护基。讨论了pH对4-C-甲基-DAB（盐的pK(a)约为8.4）核磁共振谱的影响，这表明在分析耦合常数和化学位移时都需要谨慎。4-C-甲基-DAB（对大鼠肠道蔗糖酶的K(i)为0.89 μM，IC(50)为0.41 μM）是一种竞争性抑制剂，而4-C-甲基-LAB（对大鼠肠道蔗糖酶的K(i)为0.95 μM，IC(50)为0.66 μM）是一种非竞争性特异性强效α-葡萄糖苷酶抑制剂。文中给出了DAB、LAB、4-C-甲基-DAB、4-C-甲基-LAB和异-DAB（但不是异-LAB）抑制α-葡萄糖苷酶的原理。二者都是内质网（ER）驻留α-葡萄糖苷酶I和II的抑制剂。
相似文献
1
4-C-Me-DAB and 4-C-Me-LAB - enantiomeric alkyl-branched pyrrolidine iminosugars - are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group.4-C-甲基-DAB和4-C-甲基-LAB（对映体烷基支链吡咯烷亚氨基糖）是特异性强效α-葡萄糖苷酶抑制剂；以丙酮作为唯一的保护基团。
Tetrahedron Lett. 2011 Jan 12;52(2):219-223. doi: 10.1016/j.tetlet.2010.10.173.
2
Design, synthesis and glycosidase inhibition of C-4 branched LAB and DAB derivatives.C-4 支链 LAB 和 DAB 衍生物的设计、合成及糖苷酶抑制活性研究。
Eur J Med Chem. 2022 Apr 5;233:114230. doi: 10.1016/j.ejmech.2022.114230. Epub 2022 Feb 25.
3
Nanomolar β-glucosidase and β-galactosidase inhibition by enantiomeric α-1-C-alkyl-1,4-dideoxy-1,4-imino-arabinitol derivatives.对映体α-1-C-烷基-1,4-二脱氧-1,4-亚氨基阿拉伯糖醇衍生物对纳摩尔级β-葡萄糖苷酶和β-半乳糖苷酶的抑制作用
Eur J Med Chem. 2023 Feb 5;247:115056. doi: 10.1016/j.ejmech.2022.115056. Epub 2022 Dec 28.
4
C-branched iminosugars: α-glucosidase inhibition by enantiomers of isoDMDP, isoDGDP, and isoDAB-L-isoDMDP compared to miglitol and miglustat.C 支链亚氨基糖：与米格列醇和米格列汀相比，异-DMDP、异-DGDP 和异-DAB-L-异-DMDP 对映异构体对 α-葡萄糖苷酶的抑制作用。
J Org Chem. 2013 Aug 2;78(15):7380-97. doi: 10.1021/jo4005487. Epub 2013 Jun 5.
5
Docking study and biological evaluation of pyrrolidine-based iminosugars as pharmacological chaperones for Gaucher disease.基于吡咯烷的亚氨基糖作为戈谢病药理伴侣分子的对接研究及生物学评价
Org Biomol Chem. 2016 Jan 21;14(3):1039-48. doi: 10.1039/c5ob02223a. Epub 2015 Dec 3.
6
Characterizing the selectivity of ER α-glucosidase inhibitors.鉴定 ERα-葡萄糖苷酶抑制剂的选择性。
Glycobiology. 2019 Jul 1;29(7):530-542. doi: 10.1093/glycob/cwz029.
7
Strategy for Designing Selective Lysosomal Acid α-Glucosidase Inhibitors: Binding Orientation and Influence on Selectivity.设计选择性溶酶体酸性α-葡萄糖苷酶抑制剂的策略：结合取向和对选择性的影响。
Molecules. 2020 Jun 19;25(12):2843. doi: 10.3390/molecules25122843.
8
Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB).高效合成赖因丁糖和 1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇（DAB）的八种立体异构体。
Carbohydr Res. 2024 Nov;545:109280. doi: 10.1016/j.carres.2024.109280. Epub 2024 Sep 19.
9
1,4-Dideoxy-1,4-imino-d-arabinitol (DAB) Analogues Possessing a Hydrazide Imide Moiety as Potent and Selective α-Mannosidase Inhibitors.具有酰肼亚胺部分的1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇（DAB）类似物作为强效和选择性α-甘露糖苷酶抑制剂。
ACS Omega. 2020 Jul 15;5(29):18507-18514. doi: 10.1021/acsomega.0c02466. eCollection 2020 Jul 28.
10
Inhibition of glycogenolysis in primary rat hepatocytes by 1, 4-dideoxy-1,4-imino-D-arabinitol.1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇对原代大鼠肝细胞糖原分解的抑制作用
Biochem J. 1999 Sep 15;342 Pt 3(Pt 3):545-50.
引用本文的文献
1
Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy.硼酸化 2,3,4,5-四氯邻苯二甲酰亚胺及其 2,3,4,5-四氯苯甲酰胺类似物的合成、糖苷酶抑制活性及其在硼中子俘获治疗中的抗癌活性。
Molecules. 2022 May 26;27(11):3447. doi: 10.3390/molecules27113447.
2
Pharmacological Chaperone Therapy for Pompe Disease.药物伴侣治疗庞贝病。
Molecules. 2021 Nov 29;26(23):7223. doi: 10.3390/molecules26237223.
3
Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis.合成与应用在囊性纤维化治疗中的亚氨基糖
Int J Mol Sci. 2020 May 9;21(9):3353. doi: 10.3390/ijms21093353.
4
Synthesis and Glycosidase Inhibition of Broussonetine M and Its Analogues.布魯森酮 M 及其類似物的合成及糖苷酶抑制活性研究。
Molecules. 2019 Oct 15;24(20):3712. doi: 10.3390/molecules24203712.
5
Synthesis of bis-Phosphate Iminoaltritol Enantiomers and Structural Characterization with Adenine Phosphoribosyltransferase.双磷酸亚氨基阿卓糖醇对映体的合成及其与腺嘌呤磷酸核糖转移酶的结构表征
ACS Chem Biol. 2018 Jan 19;13(1):152-160. doi: 10.1021/acschembio.7b00601. Epub 2017 Dec 14.
6
Roscovitine is a proteostasis regulator that corrects the trafficking defect of F508del-CFTR by a CDK-independent mechanism.罗斯考维汀是一种蛋白质稳态调节剂，它通过一种不依赖细胞周期蛋白依赖性激酶的机制纠正F508del-CFTR的转运缺陷。
Br J Pharmacol. 2014 Nov;171(21):4831-49. doi: 10.1111/bph.12859.
7
Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.囊性纤维化支气管上皮细胞被膜棕榈酸酯蓄积导致脂毒性。
PLoS One. 2014 Feb 19;9(2):e89044. doi: 10.1371/journal.pone.0089044. eCollection 2014.
8
2-N-Benzyl-2,6-dide-oxy-2,6-imino-3,4-O-isopropyl-idene-3-C-methyl-d-allono-nitrile.2-N-苄基-2,6-二脱氧-2,6-亚氨基-3,4-O-异丙叉基-3-C-甲基-D-阿洛糖腈
Acta Crystallogr Sect E Struct Rep Online. 2012 May 1;68(Pt 5):o1474. doi: 10.1107/S1600536812016273. Epub 2012 Apr 21.
9
6-De-oxy-3,4-O-isopropyl-idene-2-C-methyl-l-galactono-1,5-lactone.6-脱氧-3,4-O-异亚丙基-2-C-甲基-L-半乳糖-1,5-内酯
Acta Crystallogr Sect E Struct Rep Online. 2011 Sep 1;67(Pt 9):o2531-2. doi: 10.1107/S1600536811034957. Epub 2011 Aug 31.
本文引用的文献
1
Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors.开发 GlcNAc 启发的亚氨基环糖醇作为有效且选择性的 N-乙酰-β-己糖苷酶抑制剂。
ACS Chem Biol. 2010 May 21;5(5):489-97. doi: 10.1021/cb100011u.
2
Cystic fibrosis transmembrane conductance regulator modulators for personalized drug treatment of cystic fibrosis: progress to date.囊性纤维化跨膜电导调节因子调节剂在囊性纤维化个体化药物治疗中的应用：最新进展。
Drugs. 2010 Feb 12;70(3):241-59. doi: 10.2165/11316160-000000000-00000.
3
The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine.Lentiginosine 非天然对映异构体的新型促凋亡活性。
Glycobiology. 2010 May;20(5):500-6. doi: 10.1093/glycob/cwp202. Epub 2010 Jan 5.
4
Synthesis and biological characterisation of novel N-alkyl-deoxynojirimycin alpha-glucosidase inhibitors.新型N-烷基-脱氧野尻霉素α-葡萄糖苷酶抑制剂的合成及生物学特性研究
Chembiochem. 2009 Apr 17;10(6):1101-5. doi: 10.1002/cbic.200900025.
5
Glycomimetics at the mirror: medicinal chemistry of L-iminosugars.镜像中的糖模拟物：L-亚氨基糖的药物化学
Curr Med Chem. 2009;16(4):473-505. doi: 10.2174/092986709787315540.
6
Sugar-mimicking glycosidase inhibitors: bioactivity and application.模拟糖的糖苷酶抑制剂：生物活性与应用
Cell Mol Life Sci. 2009 May;66(9):1479-92. doi: 10.1007/s00018-008-8522-3.
7
A cystic fibrosis respiratory epithelial cell chronically treated by miglustat acquires a non-cystic fibrosis-like phenotype.用米格列醇长期治疗的囊性纤维化呼吸道上皮细胞呈现出非囊性纤维化样表型。
Am J Respir Cell Mol Biol. 2009 Aug;41(2):217-25. doi: 10.1165/rcmb.2008-0285OC. Epub 2009 Jan 8.
8
Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases.五元糖类似物对哺乳动物糖原降解酶和各种糖苷酶的影响。
Bioorg Med Chem. 2008 Mar 15;16(6):2734-40. doi: 10.1016/j.bmc.2008.01.032. Epub 2008 Jan 26.
9
Glucosylated free oligosaccharides are biomarkers of endoplasmic- reticulum alpha-glucosidase inhibition.糖基化游离寡糖是内质网α-葡萄糖苷酶抑制作用的生物标志物。
Biochem J. 2008 Jan 15;409(2):571-80. doi: 10.1042/BJ20070748.
10
Discovery of pyrrolo[2,3-b]pyrazines derivatives as submicromolar affinity activators of wild type, G551D, and F508del cystic fibrosis transmembrane conductance regulator chloride channels.吡咯并[2,3 - b]吡嗪衍生物作为野生型、G551D和F508del囊性纤维化跨膜传导调节因子氯离子通道亚微摩尔亲和力激活剂的发现。
J Pharmacol Exp Ther. 2006 Oct;319(1):349-59. doi: 10.1124/jpet.106.104521. Epub 2006 Jul 7.
Zotero 插件