Synthesis Of Tenatoprazole And Biapenem

Part 1 depict synthesis of Tenatoprazole and enantiomeric Tenatoprazole.Proton pump inhibitor is the enzyme responsible for the transport of gastric acid into the lumen of the stomach. Three proton pump inhibitors have been launched: omeprazole, lansoprazole and pantoprazole in 1988,1991 and 1994, respectively. Tenatoprazole chemical name is 5-methoxy-2-(4-methoxy-3,5-dimethylpyridin-2-yl-methylsulfinyl)imidazo[4,5-6]pyridine. Compared with other similar drugs, Tenatoprazole is showed to markedly inhibit H+/K+-ATPase activity in vitro, to be active in various experiment ulcer models, and to have excellent storage stability. We use a concise route to synthesize it. From 2,6-dichloropyridine as starting material, we can get the target molecule through nitration, substitution, reduction, cyclization, oxidation etc. After optimization, the yield of total synthesis reaches 40%. On the basis of completing synthesis of Tenatoprazole, we try to synthesize enantiomeric Tenatoprazole. After using different ratio of (S,S)-DET, water, (i-Pr)₂NEt, Ti(Oi-Pr)4 and CHP to asymmetrically oxide sulfide, the best result we got is 35% ee product, which hadn't been report yet by now .Part 2 depict synthesis of side chain of biapenem 2.In the late 1970s, a new class of β-lactams, the carbapenems, was identidied. It possesses antibacterial activities against a wide range of Gram-positive and negative bacteria. Biapenem [Lederle (Japan), Ltd] is a new 1β-methylcarbapenem whose chemical name is (1R,5S,6S )-2-[(6,7-dihydro-5H-pyrazolo[l,2-α][l,2,4]triazolium-6-yl)- thio] -6-[(R)-l-hydroxyethyl] -l-methylcarbapen-2-em-3-carboxylate. Compared with imipenem/ cilastatin, It is more stable to human renal dehydropeptidase-1 (DHP-1) and therefore does not require the co-administration of a DHP-1 enzyme inhibitor because of existence of 1(3 methyl. We had completed synthesis of side chain of biapenem 2 and optimized the original synthesis, which made operation easy and production convenient in industry. Moreover, we mention a new and concise route, which will greatly improve efficiency. This work is carrying out.