10.1021/acs.orglett.8b02900
The research describes the total synthesis of (±)-quinagolide, a D2 receptor agonist used for treating elevated prolactin levels. The synthesis was achieved through a ceric ammonium nitrate (CAN)-mediated regioselective azidoalkoxylation of enol ether route, which allowed for the rapid construction of the piperidine ring and the nitrogen-containing side chain of quinagolide. Key steps in the process included the PPTS-catalyzed one-pot acetal deprotection followed by a diastereoselective Henry reaction, which enabled the construction of the required trans ring junction. The study also highlighted the first-of-its-kind synthesis of the 3-azidopiperidine skeleton using CAN-mediated regioselective azidoalkoxylation of enol ether. Chemicals used in the process included meta-hydroxybenzaldehyde, allyl bromide, K2CO3, dimethyl sulfate, 2,2-dimethyl-1,3-propanediol, OsO4-NMO, NaIO4, Wittig reagents, DBU, nitromethane, PPTS, FeCl3, PTSA, pyridine, DIBAL-H, MOM Wittig salt, potassium t-butoxide, NaN3, and various other reagents and solvents necessary for the reactions and purification steps. The synthesis concluded with the demethylation of compound 20 to afford quinagolide 4, with the analytical and spectral data obtained for quinagolide 4 being in complete agreement with the reported data.
10.1021/op400317z
The study presents an improved route for the synthesis of a MET kinase inhibitor, LY2801653, which is a small molecule with potential therapeutic applications in various types of cancers. The new synthesis process is more efficient, yielding a 22% overall yield over eight steps, compared to the initial 12-step process with a 5.4% yield. Key steps in the process include a Cu-catalyzed cyclization to form an N1-methylindazole ring, selective nitro reduction, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection. The chemicals used in the study serve various purposes: 3-hydroxybenzaldehyde as the starting material, copper catalyst for cyclization, nitrobenzene for the formation of aryl ether, and Boc-protected pyrazole as a key intermediate. The study also addresses safety concerns and optimizes the synthesis for multikilogram operations, focusing on minimizing the use of hazardous chemicals and improving the overall efficiency of the process.
Xi
Xi:Irritant;
