Process Development for the Synthesis of a Monobactam Antibiotic - LYS228

ABSTRACT: A scalable process for a novel monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in multiple kilograms scale. An alternative approach to compound 7 without protecting group exchange has been demonstrated to enable a shortened synthesis. A scalable process for the side chain 20 which used an alternative reagent to mitigate a safety risk from the initial med-chem approach was performed. The final assembling to LYS228 to a stable isolated product was identified and executed in multiple kilogram scale.