Regioselective Activation of Aminothiazole(iminoxyacetic acid)acetic Acid: An Efficient Synthesis of the Monobactam Aztreonam
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- 作者：Janak Singh ; Theodor W. Denzel ; Rita Fox ; Thomas P. Kissick ; Rolf Herter ; Joseph Wurdinger ; Peter Schierling ; Chris G. Papaioannou ; Jerome L. Moniot ; Richard H. Mueller ; and Christopher M. Cimarusti
- 刊名：Organic Process Research & Development
- 出版年：2002
- 出版时间：November 2002
- 年：2002
- 卷：6
- 期：6
- 页码：863 - 868
- 全文大小：114K
- 年卷期：v.6,no.6(November 2002)
- ISSN：1520-586X
文摘
An efficient synthesis of the monobactam aztreonam [[2S-[2
,3
(Z)]]-3[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-methyl-4-oxo-1-azetidinesulfonic acid](1) by acylation of -aminoazetidinone 22 with the regioselectively activated aminothiazoleiminoxyacetic diacid 15 or 18 isdescribed. Reaction of benzhydryl ester 10 with N-hydroxybenzotriazole and dicyclohexylcarbodiimide followed by esterdeprotection formed the monoacid amide 15. Alternatively,chemoselective transient silylation of the diacid 9 followed byactivation with N-hydroxysuccinimide formed active ester 18.Acylation of -aminoazetidinone 22 with amide 15 or ester 18produced aztreonam (1) in 75-85% yield.
,3(Z)]]-3[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-methyl-4-oxo-1-azetidinesulfonic acid](1) by acylation of -aminoazetidinone 22 with the regioselectively activated aminothiazoleiminoxyacetic diacid 15 or 18 isdescribed. Reaction of benzhydryl ester 10 with N-hydroxybenzotriazole and dicyclohexylcarbodiimide followed by esterdeprotection formed the monoacid amide 15. Alternatively,chemoselective transient silylation of the diacid 9 followed byactivation with N-hydroxysuccinimide formed active ester 18.Acylation of -aminoazetidinone 22 with amide 15 or ester 18produced aztreonam (1) in 75-85% yield.