1448706-36-2Relevant articles and documents
Practical Gram-Scale Synthesis of Iboxamycin, a Potent Antibiotic Candidate
Mason, Jeremy D.,Myers, Andrew G.,Pote, Aditya R.,Terwilliger, Daniel W.
supporting information, p. 11019 - 11025 (2021/08/03)
A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation-oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp3-sp2 Negishi coupling, and a one-pot transacetalization-reduction reaction to form the target compound's oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its in vivo profiling in murine models of infection.
FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF
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Page/Page column 107-108, (2020/05/29)
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
Scale-up Synthesis of Tesirine
Tiberghien, Arnaud C.,Von Bulow, Christina,Barry, Conor,Ge, Huajun,Noti, Christian,Collet Leiris, Florence,McCormick, Marc,Howard, Philip W.,Parker, Jeremy S.
, p. 1241 - 1256 (2018/09/06)
This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.