Tilmicosin, structure

This selected ion monitoring (SIM) approach typically has greater applicability in cases where sensitivity is more of a concern. Kiehl and Kennington developed a swine liver confirmatory method for tilmicosin that confirmed structure based upon monitoring a parent ion and two additional structural fragment ions. A discussion of the validation requirements for confirmatory methods is provided in Section 6. 

Micotil or Tilmicosin 127, a 1-substituted 3,5-lupitidine (85 15 mixture of dsjtrans-isomers), is used as an antibacterial agent against calf pneumonia. The macrolide component of micotil is structurally related to the antibacterial compound tylosin <1993JAVMA273>. 

Figm-e 1. Structure of tilmicosin (R=CH3) and metabolite T-1 0 =H). Note Positions of labeling of macrolide ring are shown by ( ). Pip- C-tilmicosin was labeled in the 2,6 positions of the piperidine ring and Eq- C-tilmicosin was labeled in the macrolide ring and the 3,5 positions of the piperidine ring. 

Identification of Compound T-2. The metabolism work on liver suggested that Compound T-2 in liver was from the dosing material rather than from metabolism. A quantity of T-2 was isolated from technical tilmicosin by countercurrent partitioning and preparative HPLC on a C-18 reversed phase column. Extensive NMR and MS analyses were conducted. The structure of T-2 that was deduced from this work is that it is a dimeric derivative of tilmicosin. A description of this work is beyond the scope of this paper and will be published later. 

Reductive amination of the aldehyde group to aminomethyl derivatives has provided another route to potentially useful compounds. An initial report described the synthesis of primary amino derivatives of tylosin and leucomycin along with dimeric structures of each [140]. A group of derivatives of tylosin and demycarosyltylosin (desmycosin) were subsequently synthesized and shown to retain antimicrobial activity [141]. From a more extensive series of compounds prepared by reductive amination of tylosin and related macrolides, 20-deoxo-20-(3,5-dimethylpiperidinyl)desmycosin was selected for further development in veterinary medicine [142]. This compound, under the generic name of tilmicosin (see Fig. 7), is being evaluated for treatment of pneumonia in cattle and pigs [143, 144, 145]. 

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