178250-23-2Relevant academic research and scientific papers
Synthesis of a Next-Generation Taxoid by Rapid Methylation Amenable for 11C-Labeling
Seitz, Joshua D.,Wang, Tao,Vineberg, Jacob G.,Honda, Tadashi,Ojima, Iwao
, p. 2847 - 2857 (2018/03/09)
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 the rapid methylation and HPLC purification of the target compound in a time frame amenable to 11C-labeling for applications to PET studies.
Syntheses and structure-activity relationships of the second-generation antitumor taxoids: Exceptional activity against drug-resistant cancer cells
Ojima, Iwao,Slater, John C.,Michaud, Evelyne,Kuduk, Scott D.,Bounaud, Pierre-Yves,Vrignaud, Patricia,Bissery, Marie-Christine,Veith, Jean M.,Pera, Paula,Bernacki, Ralph J.
, p. 3889 - 3896 (2007/10/03)
A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the β-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synth
