The synthesis of an aza-cryptophycin analogue is described, featuring a highly trans-selective ring-closing metathesis reaction and an asymmetric Corey−Chaykovsky-type reaction to install the epoxide function. This latter reaction is an answer to the long-standing synthetic challenged posed by the efficient formation of the epoxide function of the cryptophycin family of compounds in a diastereoselective manner. It allows for a one-third reduction in the number of steps compared with the previously used synthesis (27 to 19 steps) and increases the overall yield of the longest linear sequence by a factor of 27 (0.6% to 16%). This fit-forpurpose synthesis allowed the production of a steady supply of the material for the early phase of a cryptophycin-based antibody− drug conjugate program.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.