Li Cong, Winnard Paul, Bhujwalla Zaver M
School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China, and JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Tetrahedron Lett. 2009 Jun 17;50(24):2929-2931. doi: 10.1016/j.tetlet.2009.03.198.
1-(acetic acid)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DOTA-Tris(t)Bu ester or 1) is a precursor chelating agent for lanthanide ions and can be efficiently labeled with various functional moieties or macromolecules to improve the targeting specificity, intracellular delivery, bio-compatibility, and pharmacokinetics of resulting contrast media used in molecular imaging. This compound is commercially available but the extremely high cost seriously limits its wide utilization. Thus, we sought a convenient and inexpensive synthesis of DOTA-Tris-(t)Bu ester that is readily adapted for use in any laboratory. The synthetic approach described here is straightforward and has an overall yield of 92%. Significantly, the product can be purified conveniently without using of a time- and labor-intensive column chromatography. Other advantages of this method, such as operational convenience, starting material availability, and atom efficiency make it very attractive to prepare DOTA-Tris-(t)Bu ester in large quantity with a reduced cost.
1-（乙酸）-4,7,10-三（叔丁氧羰基甲基）-1,4,7,10-四氮杂环十二烷（DOTA-三（叔丁基）酯或1）是一种镧系离子的前体螯合剂，可有效地用各种功能部分或大分子进行标记，以提高分子成像中所用造影剂的靶向特异性、细胞内递送、生物相容性和药代动力学。该化合物有商业供应，但极高的成本严重限制了其广泛应用。因此，我们寻求一种简便且廉价的DOTA-三（叔丁基）酯合成方法，该方法易于在任何实验室中使用。这里描述的合成方法简单直接，总产率为92%。重要的是，产物无需使用耗时费力的柱色谱法即可方便地纯化。该方法的其他优点，如操作便利性、起始原料可得性和原子经济性，使其非常适合以降低成本大量制备DOTA-三（叔丁基）酯。
