β-ラクタム系抗生物質の重要中間体の合成プロセス開発

抄録

It is well-known that (3R, 4R) -4-acetoxy-3- [(R) -1'- ((t-butyldimethylsilyl) oxy) ethyl] -2-azetidinone (4-AA) and (3S, 4S) - [(R) -1'- (t-butyldimethylsilyl) oxyethyl] -4- (R) -1-carboxyethyl-2-azetidinone (1β-methylcarboxylic acid) are very important intermediates for the synthesis of carbapenems and 1β-methyl carbapenems.
We have developed the industrial processes for the syntheses of these intermediates. The synthesis of 4-AA was accomplished by the use of the ruthenium-BINAP complex catalyzed asymmetric hydrogenation of methyl 2-benzamidomethyl-3-oxobutanoate followed by the cyclization to β-lactam and the ruthenium catalyzed acetoxylation of β-lactam as the key technologies. In addition, for the synthesis of 1β-methylcarboxylic acid, we have developed three processes which involve a palladium catalyzed deallyloxycarbonylation, a rhodium catalyzed asymmetric hydroformylation and a magnesium enolate addition reaction as the key reaction, respectively.