合成具有DOTA官能基之含硼Ugi衍生物

因為我們的目標是通過使用Ugi四組分反應（Ugi 4-CR）來合成多種含硼類似物。這種目標產物物我們預計將使其具有一下四個關鍵特徵：（a）模擬di-peptide骨架的鹼性代謝過程（允許化合物通過POT途徑轉運）；（b）羰基組分（這將增加總體硼含量/分子）；（c）兩個硼酸基團（可以形成具有特殊親水性的硼酸-果糖複合物）；和（d）DOTA附屬物（允許Ugi-4CR類似物被放射性同位素標記，例如177Lu和111In）。這樣的一種設計思路可以讓我們的目標產物具有診斷與治療一體化的效果，最後我們通過合成含硼Ugi-4CR前體再與DOTA進行peptide coupling以合成多重含硼寡肽嘗試使用我們實驗室自己合成出的更為複雜的isocyanide進行合成，我們成功合成出了產物6（Fig 9），並且通過了MASS和NMR檢測。我也希望可以引入氟原子以便提高我們的目標產物的代謝效率，所以我們設計並合成了以下兩種目標物4.5分別在我們的Ugi起始物中的acid或aldehyde中加入F官能基。

關鍵字

Ugi四組分反應； DOTA

並列摘要

We aim to synthesize libraries of multiple boron-containing analogs by employing Ugi-four component reaction (Ugi 4-CR) (Scheme 1). These Ugi-4CR analogs would possess four key signatures: (a) a di-peptide skeleton that mimic basic metabolite (that allows the compound to be transported via POT pathway); (b) a carboranyl component (that would increase the overall boron-content/ molecule); (c) two boronic acids groups (that could form the boronic acid-fructose complex with exceptional hydrophilicity); and (d) a DOTA appendage (that allows the Ugi-4CR analogs to be labeled by radioactive isotopes, such as 177Lu and 111In).Such a design idea can make our target product have the effect of integration of diagnosis and treatment, Finally, we synthesized the boron-containing ugi-4cr precursor and then combined it with dota to synthesize multiple boron-containing oligopeptides We tried to use the more complex isocyanide synthesized by our own laboratory to synthesize. We successfully synthesized the product 6 (Fig. 9), and passed the mass and NMR test. I also hope to introduce fluorine atoms to improve the metabolic efficiency of our target products, so we designed and synthesized the following two targets 4.5 to add f functional groups to acid or aldehyde in our UGI initiator respectively.

並列關鍵字

Ugi-four component reaction ； DOTA

參考文獻

[1] Zhang Zizhu,Jin Congjun,Liu Kai.Neutron capture therapy clinical development in the world[J].Enngineering science,2012,9(8);100-105

Google Scholar

[2]Cruickshank G S,Ngoga D.Detta A,et al.A cancer research UK pharma-cokinetic study of BPA-mannitol in patients with high grade glioma of optimize uptake parameters of clinical trials of BNCT[J].Apple Rabit Isot,2009,67(7-8 Suppl);S31-S33