4 research outputs found
Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YCâ17
YCâ17 is a 12âmembered ring macrolide antibiotic produced from Streptomyces venezuelae ATCC 15439 and is composed of the polyketide macrolactone 10âdeoxymethynolide appended with Dâdesosamine. In order to develop structurally diverse macrolactam analogues of YCâ17 with improved therapeutic potential, a combined approach involving chemical synthesis and engineered cellâbased biotransformation was employed. Eight new antibacterial macrolactam analogues of YCâ17 were generated by supplying a novel chemically synthesized macrolactam aglycone to S. venezuelae mutants harboring plasmids capable of synthesizing several unnatural sugars for subsequent glycosylation. Some YCâ17 macrolactam analogues were active against erythromycinâresistant bacterial pathogens and displayed improved metabolic stability in vitro. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/1/adsc_201500250_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/2/2697_ftp.pd
Copper-Catalyzed ChanâLam Coupling between Sulfonyl Azides and Boronic Acids at Room Temperature
A mild
and efficient method for the synthesis of <i>N</i>-arylsulfonamides
in the presence of 10 mol % of CuCl is demonstrated.
The reaction proceeds readily at room temperature in an open flask
using a variety of sulfonyl azides and boronic acids without any base,
ligand, or additive