Synthesis and Crystal Structure of Tianagliflozin Triacetate

The title compound tianagliflozin triacetate 1 was synthesized and its crystal structure was determined by single-crystal X-ray diffraction.The crystal belongs to monoclinic system(C27H31ClO8,Mr = 518.97),space group P21 with a = 5.3913(11),b = 16.137(2),c = 15.411(3) ,β = 94.15(3)°,V = 1337.3(5) 3,Z = 2,Dc = 1.289 g/cm3,F(000) = 548,μ = 0.190 mm-1,the final R = 0.0374 and wR = 0.0809 for 3981 observed reflections(I 2σ(I)).The structure of 1,triacetate of a highly potent SGLT2 inhibitor tianagliflozin,was unambiguously determined by single-crystal X-ray diffraction,which helped to confirm the desired β configuration at the anomeric center and the position where the deoxylation occurred.The two benzene rings in the lattice are basically orthogonal to each other.There are four intermolecular hydrogen bonds in the crystal,which helps to further stabilize the crystal.     

基于基础化学知识切入的药理学课程改革探索与实践*

由于基础化学知识强、医学知识弱,药学专业的学生在学习药理学知识时更易出现难记忆、难理解、难应用的问题。为此,教学团队基于药学专业学生的知识背景,从基础化学知识切入展开药理学教学,着重从药理学知识掌握和应用、分析解决问题的能力以及课程思政等方面进行课程改革,并从课堂趣味性、学生参与度、能力培养、辩证思维和知识水平测试初步评价课改效果。结果显示,基于基础化学知识切入的药理学授课能够有效提升药理学教学效果和质量。     

Synthesis and Crystal Structure of 2,3,4,6-tetra-O-Acetyl-1-{4-chloro-3-[1-（4-ethoxyphenyl）-1-methylethyl]phenyl}-1-deoxy-β-D-glucopyranose

The title compound was synthesized and its crystal structure was determined by single-crystal X-ray diffraction.The crystal is of monoclinic system(C31H37ClO10,Mr = 605.06),space group P21 with a = 11.882(5),b = 10.106(5),c = 13.816(6),V = 1545.9(12)3,Z = 2,Dc = 1.300 g/cm3,F(000) = 640,μ = 0.179 mm-1,the final R = 0.0430 and wR = 0.0595 for 4960 observed reflections(I > 2σ(I)).The title compound was confirmed to be a β-anomer by single-crystal X-ray diffraction and 1H NMR.The proximal benzene ring is nearly orthogonal to the glucopyranoside ring,and the two benzene rings are also almost orthogonal to each other.Four non-classical intermolecular hydrogen bonds observed in the crystal lattice help to stabilize the crystal.     

基于葛根素结构的SGLT2抑制剂的设计、合成与体外生物活性研究

合成了一系列葛根素衍生物,采用稳定表达钠-葡萄糖协同转运蛋白2(human sodium-dependent glucose cotransporter 2,h SGLT2)的中国仓鼠卵巢细胞(Chinese hamster ovary,CHO)和~(14)C-甲基葡萄糖苷为底物评价衍生物体外抑制SGLT2的活性.葛根素衍生物具有显著的抑制SGLT2的活性,部分葛根素双取代衍生物的IC_(50)(hSGLT2)可达20~30 nmol·L~(-1),是葛根素活性的40~60倍.单取代衍生物如正己基葛根素(1i)、正辛基葛根素(1j)、对甲基苄基葛根素(1l)和对甲氧基苄基葛根素(1m)也表现出很强的抑制SGLT2活性,且保留了7-OH结构,可能保留了母核葛根素抗氧化、调血脂的药理活性,这对糖尿病及其心血管并发症的治疗是有利的.     

6-羟基脱氧Canagliflozin的合成及其生物活性

以Canagliflozin(1)为起始原料,经7步反应合成了其6-OH脱氧产物4-(6-脱氧-β-D-吡喃葡萄糖基)-2-[5-(4-氟苯基)噻吩-2-甲基]-1-甲基苯(8),8是与母体1相似的新型SGLT2抑制剂,总收率21%,其结构经1H NMR,13C NMR和MS表征。体外生物活性测试结果显示,1和8对hSGLT2的IC50分别为3.9 nM和4.8nM,对SGLT1的选择性(SGLT2/SGLT1)分别为178和194。在大鼠尿糖排泄实验(UGE)中8具有很强的尿糖排泄作用,与母体1并无显著性差异。