Versatile synthesis of pathogen specific bacterial cell wall building blocks

Full details on the design, strategies and tactics for development of a novel synthetic sequence to farnesyl lipid I and II analogs is reported. The modular route was based on a three coupling strategy involving an efficient solid phase synthesis of the elaborate peptide fragment, which proceeded with excellent yield and stereoselectivity and was efficiently applied for the convergent synthesis of 3-lipid I and II. Furthermore, the generality of this route was demonstrated by synthesis of 3-lipid I congeners that are characteristic for S. aureus and E. faecalis . All 3-lipid I and II building blocks were obtained in high purity revealing high spectroscopic resolution. A modular three coupling strategy involving a versatile solid phase peptide synthesis enables access to pathogen specific lipid analogs in high yield, revealing high spectroscopic resolution of these key bacterial cell wall building blocks.