Organic Process Research & Development · 2010 · 10 citations · 8 references
PharmacyMedicinal ChemistryDrug DesignDrug DiscoverySynthetic Medicinal ChemistryLead Compound DesignLead DiscoveryMacrocycle SynthesisAntibiotic DiscoveryChemical Synthesis Of AnaloguesColumn ChromatographyLead Compound DiscoveryLead Discovery From Natural ProductsMedicinal Chemistry ApplicationsNovel Antibacterial AgentsNovel Antibacterial Drug Discovery
Macrolones are a novel class of potent antimicrobial agents that consist of a macrolide scaffold to which a quinolone unit is tethered by various linkers to the 4′′- O -position of the cladinose sugar. In this paper is described a modified 13-step route to a lead compound in the series. Critical reaction steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, a synthetic procedure suitable for preparation of multihundred gram quantities of the final product, with 98% purity, has been developed. The new procedure does not require any purification by column chromatography for any of the reaction steps. The overall yield was increased from 5−8% in the medicinal chemistry route to 27% in the improved procedure.
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