Synthesis of Substrates and Biochemical Probes for Study of the Peptidoglycan Biosynthetic Pathway

Several widely used antibiotics such as beta-lactams, glycopeptides, and lipoglycopeptides exhibit their activity by interfering with peptidoglycan biosynthesis. Ever-increasing resistance to these and other agents has placed a renewed emphasis on the need to understand the reactions in this bio-synthetic pathway at the molecular level. While efficient access to many of the biosynthetic enzymes has been gained, the isolation of their natural substrates has proven difficult. Chemical synthesis has provided valuable tools to circumvent this problem and has allowed convenient access to several key intermediates and analogs thereof. Recent advances in the synthesis of the late-stage intermediates, including the Park nucleotide, lipid I, lipid II, fragments of the bacterial cell wall, along with other biochemical probes are reviewed. A brief discussion on the use of these substrates in study of this important biosynthetic pathway is also included.