Synfacts 2020; 16(06): 0619
DOI: 10.1055/s-0040-1707529
DOI: 10.1055/s-0040-1707529
Synthesis of Natural Products and Potential Drugs
Synthesis of Monobactam Antibiotic LYS228
Cheung CM.
* et al. Suzhou Novartis Pharma Technology Co. Ltd., Changshu, P. R. of China
Process Development for the Synthesis of a Monobactam Antibiotic – LYS228.
Org. Process Res. Dev. 2020;
24: 363-370
Process Development for the Synthesis of a Monobactam Antibiotic – LYS228.
Org. Process Res. Dev. 2020;
24: 363-370
Further Information
Publication History
Publication Date:
15 May 2020 (online)
Key words
LYS228 - monobactam antibiotic - asymmetric synthesis - [2+2] cycloaddition - Staudinger β-lactam synthesis
Significance
LYS228 is a monobactam antibiotic that inhibits cell-wall synthesis in Gram-negative bacteria through covalent modification of the active-site serine of penicillin-binding protein 3. It is active in vitro and in vivo against Enterobacteriaceae, and it is stable to most serine-β-lactamases and all metallo-β-lactamases profiled to date.
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Comment
The key step in the manufacturing process for LYS228 depicted is the asymmetric Staudinger β-lactam synthesis involving a [2+2] cycloaddition of a ketene derived from C with aldimine B derived from (S)-glyceraldehyde acetonide A (C. Hubschwerlen, J.-L. Specklin Org. Synth. 1995, 72, 14). For the discovery synthesis, see: Bioorg. Med. Chem. Lett. 2018, 28, 7748.
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