Synthesis of homochiral tris(2-alkyl-2-aminoethyl)amine derivatives from chiral α-amino aldehydes and their application in the synthesis of water soluble chelators
Synthesis of homochiral tris(2-alkyl-2-aminoethyl)amine derivatives from chiral α-amino aldehydes and their application in the synthesis of water soluble chelators
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DOI：
10.1021/ic001021x
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发表时间：
2001-06-18
影响因子：
4.6
通讯作者：
Raymond, KN
中科院分区：
文献类型：
--
作者：
Hajela, SP;Johnson, AR;Raymond, KN
报道了一种三重对称的纯手性三（2-烷基-2-氨乙基）胺（TREN）衍生物的合成方法。该合成在范围上是通用的，从容易制备的手性α-氨基：醛开始。用旋光法和手性NMR化学位移实验确定了N-BOC保护的三（2-甲基-2-氨乙基）胺和三（2-羟甲基-2-氨乙基）胺衍生物的光学纯度。用X射线衍射法研究了三（2-甲基-2-氨乙基）胺的L-丙氨酸衍生物（3 HCl，L-Ala（3）-TREN）的晶体。是立方的，空间群P2（1）3，晶胞尺寸为a11.4807（2）埃，V = 1513.23（4）埃（3），Z = 4。三丝氨酸衍生的骨架tris的连接（2-羟甲基-2-氨基乙基）胺（L-Ser（3）-TREN）合成三个3-羟基-1-甲基-2（1H）-吡啶酸酯（3）部分，然后与Gd（III）络合，得到络合物Gd（L-Ser（3）-TREN-Me-3，2-HOPO）（H2O）（2），其比母体Gd更易溶于水（TREN-Me-3，2-HOPO）（H2O）（2）是磁共振成像（MRI）应用的有前途的候选物。手性铁配合物Fe（L-Ser（3）-TREN-Me-3，2-HOPO）的晶体为正交晶系，空间群为P2（1）2（1）2（1），晶胞参数a = 13.6290（2）埃，B = 18，6117（3）埃，c = 30.678963）埃; V = 7782.0（2）埃（3），Z = 8。用圆二色性光谱研究了铁配合物的溶液构象。用电位法和分光光度法研究了该配体及其铁（Ⅲ）和钆（Ⅲ）配合物的配位化学。与先前研究的多齿3，2-HOPO-4-甲酰胺配体的质子化常数相比，L-Ser（3）-TREN-Me-3，2-HOPO（24.78）的质子化常数之和（log β（014））比母体TREN-Me-3，2-HOPO酸性大1.13 log单位。用分光光度pH滴定法测定了铁（III）和钆（III）配合物的形成常数，分别为（log K）、26.3（1）和17.2（2）。
A novel synthesis of 3-fold symmetric, homochiral tris(2-alkyl-2-aminoethyl)amine (TREN) derivatives is presented. The synthesis is general in scope, starting from readily prepared chiral alpha -amino: aldehydes. The optical purity of the N-BOC protected derivatives of tris(2-methyl-2-aminoethyl)amine and tris(2-hydroxymethyl-2-aminoethyl) amine has been ascertained by polarimetry and chiral NMR:chemical shift experiments. An X-ray diffraction study of the L-alanine derivative of tris(2-methyl-2-aminoethyl)amine .3 HCl, L-Ala(3)-TREN) is presented:: crystals grown from ether diffusion into methanol. are cubic, space group P2(1)3 with unit cell dimensions a 11.4807(2) Angstrom, V = 1513.23(4) Angstrom (3), and Z = 4. Attachment of the triserine derived backbone tris(2-hydroxymethyl-2-aminoethyl)amine (L-Ser(3)-TREN) to three 3-hydroxp-1-methyl-2(1H)-pyridinonate(3 moieties, followed by complexation with Gd(III) gives the complex Gd(L-Ser(3)-TREN-Me-3,2-HOPO)(H2O)(2), which is more water soluble than the parent Gd(TREN-Me-3,2-HOPO)(H2O)(2) and a promising candidate for magnetic resonance imaging (MRI) applications. Crystals of the chiral ferric complex Fe(L-Ser(3)-TREN-Me-3,2-HOPO) grown from ether/ methanol are orthorhombic, space group P2(1)2(1)2(1), With unit cell dimensions a = 13.6290(2) Angstrom, b = 18,6117(3) Angstrom, c = 30.678963) Angstrom; V = 7782.0(2) Angstrom (3), and Z = 8. The solution conformation of the ferric complex has been investigated by circular dichroism spectroscopy. The coordination chemistry of this new ligand and its iron(III) and gadolinium(III) complexes has been studied by potentiometric and spectrophotometric methods. Compared to the protonation constants of previously studied polydentate 3,2-HOPO-4-carboxamide ligands, the sum of protonation constants (log beta (014)) Of L-Ser(3)-TREN-Me-3,2-HOPO (24.78) is more acidic by 1.13 log units than the parent TREN-Me-3,2-HOPO. The formation constants for the iron(III) and gadolinium(III) complexes have been evaluated by spectrophotometric pH titration to be (log K), 26.3(1) and 17.2(2), respectively.