The vancomycin family of natural products have become increasingly important therapeutic agents in the treatment of Gram-positive bacterial infections caused by methicillin resistant Staphylococcus aureus and bacterial infections. In light of the recent emergence of vancomycin resistance in the clinic as well as the remarkable biological activity of the vancomycin family of antibiotics, the structural complexity, and the interest in elucidating the structure-biological activity relationships (SAR), the development of a practical synthetic approach to vancomycin is a highly desirable objective. The primary target is to discover novel general synthetic methods, in conjunction with reliable known protocols, to form the highly strained biaryl 12-membered AB ring in vancomycin, the most challenging aspect of any projected synthesis of this family of natural products. An additional goal is to elucidate the most efficient order for the installation of the AB, CD, and DE rings via biaryl and diphenyl ether linkages in vancomycin, an important and unexplored area. The ultimate aim is to accomplish the first total synthesis of the vancomycin aglycone in a convergent fashion.
| Wu, Jason; Young, Michael; Lewis, Amanda H et al. (2017) Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix. Cell Rep 21:2357-2366 |
