Aztreonam, Corus-1020, SQ-26776, Primbactam, Azactam

合成路线: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.

参考文献标题:Aztreonam
文献作者:Castar,J.; Blancafort,P.; Serradell,M.N.
参考来源:Drugs Fut 1983,8(4),295


合成路线: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.
参考文献标题:Regioselective activation of aminothiazole(iminoxyacetic acid)acetic acid: An efficient synthesis of the monobactam aztreonam
文献作者:Fox,R.; Denzel,T.W.; Singh,J.; et al.
参考来源:Org Process Res Dev 2002,6(6),863


产品链接: CAS No. 78110-38-0››