Identification, Characterization, Synthesis, and Strategy for Minimization of Potential Impurities Observed in the Synthesis of Solithromycin

Abstract

Potential causes for the formation of synthetic impurities that are present in solithromycin (1) during laboratory development are studied in the article. These impurities were monitored by HPLC, and their structures are identified on the basis of MS and NMR spectroscopy. In addition to the synthesis and characterization of these seven impurities, strategies for minimizing them to the level accepted by the International Conference on Harmonization (ICH) are also described.

5-Iodo-1H-1,2,3-triazoles as Versatile Building Blocks

“…51,52 This process, in particular, should be monitored in the synthesis of drugs, as illustrated in the case of solithromycin (Solithera ® ). 53 Currently Routes A and B are the most useful tools for the construction of 5-iodotriazoles due to the simplicity of the procedures, accessibility of the starting materials, and their tolerance to various functional groups. However diazotization (Route D), [54][55][56] lithiation followed by metal-iodine exchange (Route E), [57][58][59][60][61] and direct iodination of triazoles (Route E) 62 are also utilized.…”

Alkali Carbonates Improve β,β-Diaryl Serine-Catalyzed Enantioselective α-Fluorination of β-Dicarbonyl Compounds

“…Asymmetric fluorination has gained significant attention in medicinal chemistry due to its high potential for enhancing biological activity. − β-Dicarbonyl compounds have been often used as key starting materials to construct biologically relevant compounds; therefore, β-dicarbonyl compounds bearing asymmetric fluorinated carbons can serve as useful building blocks for fluorinated medicines. , For this purpose, many transition-metal-catalyzed and organocatalyzed enantioselective α-fluorinations of β-dicarbonyl compounds have been explored to date. − For example, the enantioselective α-fluorination of both acyclic and cyclic β-ketoesters has been extensively investigated using transition-metal catalysis, which often shows excellent enantioselectivity.…”