Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics

Abstract

Muraymycins, isolated from a culture broth of Streptomyces sp., are members of a class of naturally occurring nucleoside antibiotics. They are strong inhibitors of the phospho-MurNAc-pentapeptide translocase (MraY), which is responsible for the peptidoglycan biosynthesis. Since MraY is an essential enzyme among bacteria, muraymycins are expected to be a novel antibacterial agent. In this review, our efforts to synthesize muraymycin D2, simplify the chemical structure, improve antibacterial spectrum, and solve the X-ray crystal structure of the muraymycin D2/MraY complex are described.

Genome Mining and Metabolomics Uncover a Rare d-Capreomycidine Containing Natural Product and Its Biosynthetic Gene Cluster

“…One such motif, represented by the cyclic guanidino-amino acids, l -capreomycidine ( 1 ) and l - epi -capreomycidine ( 2 ), has been previously identified within a limited range of actinomycete natural products (Figure ). − For example, l -capreomycidine ( 1 ) is incorporated into the tuberactin antibiotics capreomycin IA ( 3 ) and viomycin ( 4 ), while l - epi -capreomycidine ( 2 ) is found within the protease inhibitor chymostatin ( 5 ) and the nucleoside-containing antibiotic muraymycin C4 ( 6 ). Guanidino functionalized metabolites generally have increased membrane permeability, and cyclization of the arginine to generate cyclic urea structures such as 1 and 2 is hypothesized to confer resistance to degradation pathways, thus making molecules possessing such motifs desirable targets for discovery. , …”

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents

“… Some potent cyclic and acyclic nucleoside analogues used as potent anti-viral agents [ 19 , 20 , 21 , 22 , 23 ]. …”

“…The chemical structures of some of the drugs mentioned above, together with other potent anti-viral agents belonging to the class of cyclic and acyclic nucleoside analogues, are discussed in Figure 1. [19][20][21][22][23]. Figure 1.…”