Synthesis of orthogonally reactive FK506 derivatives via olefin cross metathesis.

ABSTRACT: Chemical inducers of dimerization (CIDs) are employed in a wide range of biological applications to control protein localization, modulate protein-protein interactions and improve drug lifetimes. These bifunctional chemical probes are assembled from two synthetic modules, which each provide affinity for a distinct protein target. FK506 and its derivatives are often employed as modules in the syntheses of these bifunctional constructs, owing to the abundance and favorable distribution of their target, FK506-binding protein (FKBP). However, the structural complexity of FK506 necessitates multi-step syntheses and/or multiple protection-deprotection schemes prior to installation into CIDs. In this work, we describe an efficient, one-step synthesis of FK506 derivatives through a selective, micr

SUBMITTER: Marinec PS 

PROVIDER: S-EPMC2758530 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature