胸苷和尿苷衍生物的三羰基铼核心配合物

Rhenium tricarbonyl core complexes of thymidine and uridine derivatives.

作者信息

Wei Lihui, Babich John, Eckelman William C, Zubieta Jon

机构信息

Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA.

出版信息

Inorg Chem. 2005 Apr 4;44(7):2198-209. doi: 10.1021/ic048301n.

DOI:10.1021/ic048301n

PMID:15792454

Abstract

Thymidine and uridine were modified at the C2' and C5' ribose positions to form amine analogues of the nucleosides (1 and 4). Direct amination with NaBH(OAc)3 in DCE with the appropriate aldehydes yielded 1-{5-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L1), 1-{5-[(bis(quinolin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L2), and 1-[3-(bis(pyridin-2-ylmethyl)amino)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione (L5), while standard coupling procedures of 1 and 4 with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (2) and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid (3) in the presence of HOBT-EDCI in DMF provided a second novel series of bifunctional chelators: 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L3), 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L4), 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L6), and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L7). The rhenium tricarbonyl complexes of L1-L4, L6, and L7, [Re(CO)3(LX)]Br (X=1-4, 6, 7: compounds 5-10, respectively), have been prepared by reacting the appropriate ligand with [NEt4][Re(CO)3Br3] in methanol. The ligands and their rhenium complexes were obtained in good yields and characterized by common spectroscopic techniques including 1D and 2D NMR, HRMS, IR, cyclic voltammetry, UV, and luminescence spectroscopy and X-ray crystallography. The crystal structure of complex 6.0.5NaPF6 displays a facial geometry of the carbonyl ligands. The nitrogen donors of the tridentate ligand complete the distorted octahedral spheres of the complex. Crystal data: monoclinic, C2, a = 24.618(3) A, b = 11.4787(11) A, c = 15.5902(15) A, beta = 112.422(4) degrees , Z = 4, D(calc) = 1.562 g/cm3.

摘要

胸腺嘧啶核苷和尿嘧啶核苷在核糖的C2'和C5'位进行修饰，形成核苷的胺类似物（1和4）。在二氯乙烷中用NaBH(OAc)3与适当的醛直接胺化，得到1-{5-[(双(吡啶-2-基甲基)氨基)甲基]-4-羟基四氢呋喃-2-基}-5-甲基-1H-嘧啶-2,4-二酮（L1）、1-{5-[(双(喹啉-2-基甲基)氨基)甲基]-4-羟基四氢呋喃-2-基}-5-甲基-1H-嘧啶-2,4-二酮（L2）和1-[3-(双(吡啶-2-基甲基)氨基)-4-羟基-5-(羟甲基)四氢呋喃-2-基]-1H-嘧啶-2,4-二酮（L5），而在DMF中，1和4与5-(双(吡啶-2-基甲基)氨基)戊酸（2）和5-(双(喹啉-2-基甲基)氨基)戊酸（3）在HOBT-EDCI存在下的标准偶联程序提供了第二个新型双功能螯合剂系列：5-(双(吡啶-2-基甲基)氨基)戊酸[(3-羟基-5-(5-甲基-4-氧代-3,4-二氢-2H-嘧啶-1-基)四氢呋喃-2-基)甲基]酰胺（L3）、5-(双(喹啉-2-基甲基)氨基)戊酸[(3-羟基-5-(5-甲基-4-氧代-3,4-二氢-2H-嘧啶-1-基)四氢呋喃-2-基)甲基]酰胺（L4）、5-(双(吡啶-2-基甲基)氨基)戊酸[2-(2,4-二氧代-3,4-二氢-2H-嘧啶-1-基)-4-羟基-5-(羟甲基)四氢呋喃-3-基]酰胺（L6）和5-(双(喹啉-2-基甲基)氨基)戊酸[2-(2,4-二氧代-3,4-二氢-2H-嘧啶-1-基)-4-羟基-5-(羟甲基)四氢呋喃-3-基]酰胺（L7）。L1-L4、L6和L7的三羰基铼配合物[Re(CO)3(LX)]Br（X = 1 - 4、6、7：分别为化合物5 - 10），是通过使适当的配体与[NEt4][Re(CO)3Br3]在甲醇中反应制备的。配体及其铼配合物以良好的产率获得，并通过包括1D和2D NMR、HRMS、IR、循环伏安法、UV和发光光谱以及X射线晶体学等常用光谱技术进行表征。配合物6·0.5NaPF6的晶体结构显示羰基配体的面式几何构型。三齿配体的氮供体完成了配合物的扭曲八面体球。晶体数据：单斜晶系，C2，a = 24.618(3) Å，b = 11.4787(11) Å，c = 15.5902(15) Å，β = 112.422(4)°，Z = 4，D(calc) = 1.562 g/cm3。