An Alternative Focus for Route Design for the Synthesis of Antibody–Drug Conjugate Payloads
2019
Tiberghien, Arnaud C. | Howard, Philip W. | Goundry, William R. F. | McCormick, Marc | Parker, Jeremy S.
An analysis of Antibody–Drug Conjugate Payload manufacturing has revealed that the majority of the cost is associated with the use of high-containment facilities for the latter stages of the synthesis. To make a significant reduction in the Cost of Goods (CoGs), a new approach to route design has been introduced which focuses on minimizing the number of steps that require high containment. This approach has been exemplified in a new synthesis of tesirine, including the first application of a ring-closing copper(I)/TEMPO aerobic oxidation to the pyrrolobenzodiazepine ring system, affording a 60% reduction in CoGs.
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