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Initial Scale-Up and Process Improvements for the Preparation of a Lead Antibacterial Macrolone Compound

2010; American Chemical Society; Volume: 14; Issue: 6 Linguagem: Inglês

10.1021/op100199t

1520-586X

Vlado Štimac, Maja Matanović Škugor, Ivana Palej Jakopović, Adrijana Vinter, Marina Ilijaš, Sulejman Alihodžić, Stjepan Mutak,

Enzyme Catalysis and Immobilization

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.