Site-Selective Derivatization and Remodeling of Erythromycin A by Using Simple Peptide-Based Chiral Catalysts

摘要

Medicinal chemistry relies on the efficient generation of analogs of lead compounds. Natural products represent a special class of leads since they have survived eons of natural selection and generally evolved to perform a specific function.[1] Yet, natural products are difficult to modify efficiently by chemical methods because of their complexity and multifunctional nature.[2] Enzymatic catalysts have been applied in this context.[3] However, the range of reactions that may be employed, and the specificities they exhibit, often lead to a limited set of natural-product analogs. Using peptide-based catalysts, we report herein unique examples of small-molecule, chiral catalyst-dependent, site-selective modifications of a natural product polyol, erythromycin A.