合成路线1

The reaction of N-tert-butoxycarbonylthreonin (I) with O-benzylhydroxylamine (II) by means of N-hydroxybenzotriazole acid dicyclohexylcarbodiimide in THF gives N-tert-butoxycarbonyl-N-benzyloxythreoninamide (III), which is cyclized by means of triphenylphosphine and diethyl azodicarboxylate in THF yielding N-benzyloxy-3-(tert-butoxycarbonylamino)-4-methylazetidin-2-one (IV). The hydrogenolysis of (IV) with H2 over Pd/C in ethanol affords 3-(tert-butoxycarbonylamino)-4-methyl-N-hydroxyazetidin-2-one (V), which is reduced with TiCl3 in ethanol - aqueous ammnonium acetate giving 3-(tert-butoxycarbonylamino)-4-methylazetidin-2-one (VI). The hydrolysis of (VI) with trifluoroacetic acid in CH2Cl2 anisole, followed by reaction with benzyl chloroformate in acetone yields 3-(benzyloxycarbonylamino)-4-methylazetidin-2-one (VII). The sulfonation of (VII) with SO3 in DMF, and treatment of the resulting product with tetrabutylammonium sulfate in CH2Cl2 affords 3-(benzyloxycarbonylamino)-4-methyl-2-oxoazetidin-1-sulfonic acid tetrabutylammonium salt (VIII), which is debenzylated by hydrogenolysis with H2 over Pd/C in DMF giving 3-amino-4-methyl-2-oxoazetidin-1-sulfonic acid tetrabutylammonium salt (IX). The condensation of (IX) with alpha-[[(1-diphenylmethoxycarbonyl)-1-methylethoxy]imino]-(2-amino-4-thiazolyl)acetic acid (X), by means of N-hydroxybenzotriazole or N-hydroxysuccinimide and dicyclohexylcarbodiimide in acetone yields 3-[[(2-amino-4-thiazolyl)[[1-(diphenylmethoxycarbonyl]-1-methylethoxy]imino]acetyl]amino]-4-methyl-2-oxoazetidine-1-sulfonic acid (XI), which is finally hydrolyzed with trifluoroacetic acid.