Strohfeldt Katja, Tacke Matthias
School of Pharmacy, The University of Reading, PO Box 224, Whiteknights, Reading, Berkshire, UK.
Chem Soc Rev. 2008 Jun;37(6):1174-87. doi: 10.1039/b707310k. Epub 2008 Apr 2.
6-Substituted fulvenes are interesting and easily accessible starting materials for the synthesis of novel substituted titanocenes via reductive dimerisation, carbolithiation or hydridolithiation reactions, which are followed by a transmetallation reaction with titanium tetrachloride in the latter two cases. Depending on the substitution pattern, these titanocenes prove to be bioorganometallic anti-cancer drugs, which have significant potential against advanced or metastatic renal-cell cancer. Patients bearing these stages of kidney cancer have a poor prognosis so far and therefore real progress in the area of metal-based anti-cancer drugs may come from this simple and effective synthetic approach. This tutorial review provides an insight into the synthesis of fulvene-derived titanocenes and their activity in preclinical experiments.
6-取代富烯是有趣且易于获得的起始原料，可通过还原二聚、碳锂化或氢锂化反应来合成新型取代二茂钛，在后两种情况下，随后会与四氯化钛进行金属转移反应。根据取代模式，这些二茂钛被证明是生物有机金属抗癌药物，对晚期或转移性肾细胞癌具有显著潜力。患有这些阶段肾癌的患者迄今为止预后较差，因此金属基抗癌药物领域的真正进展可能来自这种简单有效的合成方法。本教程综述深入介绍了富烯衍生二茂钛的合成及其在临床前实验中的活性。
