Synthesis of a Next-Generation Taxoid by Rapid Methylation Amenable for 11C-Labeling
| Autor: | Tadashi Honda, Jacob G. Vineberg, Tao Wang, Joshua D. Seitz, Iwao Ojima |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Organic Chemistry. 83:2847-2857 |
| ISSN: | 1520-6904 0022-3263 |
| Popis: | Next-generation taxoids, such as SB-T-1214, are highly potent cytotoxic agents that exhibit remarkable efficacy against drug-resistant tumors in vivo, including those that overexpress the P-glycoprotein (Pgp) efflux pump. As SB-T-1214 is not a substrate for Pgp-mediated efflux, it may exhibit a markedly different biodistribution and tumor-accumulation profile than paclitaxel or docetaxel, which are both Pgp substrates. To investigate the biodistribution and tumor-accumulation levels of SB-T-1214 using positron emission tomography (PET), a new synthetic route has been developed to allow the incorporation of 11C, a commonly employed positron-emitting radionucleide, via methyl iodide at the last step of chemical synthesis. This synthetic route features a highly stereoselective chiral ester enolate–imine cyclocondensation, regioselective hydrostannation of the resulting β-lactam, and the Stille coupling of the novel vinylstannyl taxoid intermediate with methyl iodide. Conditions have been established to allow... |
| Databáze: | OpenAIRE |
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