Highly Efficient Synthesis of a Staphylococcus aureus Targeting Payload to Enable the First Antibody-Antibiotic Conjugate.
Chemistry
; 24(12): 2837-2840, 2018 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-29164727
ABSTRACT
A practical synthesis of the complex payload for an anti-Staphylococcus aureus THIOMABTM antibody-antibiotic conjugate (TAC) is described. The route takes advantage of a delicate oxidative condensation, achieved using a semi-continuous flow procedure. It allows for the generation of kilogram quantities of a key intermediate to enable a mild nucleophilic aromatic substitution to the tertiary amine free drug. The linker component is introduced as a benzylic chloride, which allows formation of the quaternary ammonium salt linker-drug. This chemical process surmounts numerous synthetic challenges and navigates deeply colored and unstable compounds to support clinical studies to counter S. aureus bacterial infections.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Staphylococcus aureus
/
Imunoconjugados
/
Antibacterianos
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos