Doxycycline is a tetracycline antibiotic that is used to treat a wide variety of infections. A mass spectrometry (MS) analytical standard with M + 4 was prepared to support pharmacology and toxicology.  Our approach was to first N-demethylate doxycycline and re-methylate using stable isotope labeled methyl-[13CD3] iodide to produce doxycycline-[13CD3].  An iron mediated Polonovsky reaction efficiently N-demethylated doxycycline.  In this process, doxcycline was oxidized to the N-oxide using m-CPBA.  The hydrochloride salt of the tertiary N-oxide was treated with Fe(0)/FeCl3 catalyst yielding the N-demethylated product.  Isolated pure demethyldoxycycline was re-methylated using diisopropyl azodicarboxylate (DIAD), polymer-supported triphenylphosphine and methyl-[13CD3] iodide.  We have synthesized labeled doxycycline with an isotopic purity of 99% using this methodology.

Synthesis of Doxycycline-[<sup>13</sup>CD<sub>3</sub>]

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Synthesis of Doxycycline-[13CD3]

Synthesis of Doxycycline-[¹³CD₃]