Total Synthesis of [14C]-Labelled Homoharringtonine

A total synthesis of enantiomerically pure [14C]‐labelled (–)‐homoharringtonine in 17 steps is reported. This synthetic process enabled the production of Good Manufacturing Practice (GMP) compliant (–)‐[14C]homoharringtonine that was used in a human mass balance study that was a post‐approval commitment to the U.S. Food and Drug Administration. (–)‐Homoharringtonine, also called omacetaxine mepesuccinate, is approved to treat adult patients with chronic myeloid leukemia (CML), a blood and bone marrow disease. In November 2012, the product was commercialised as Synribo® in the U.S., marketed by Teva Pharmaceuticals. The total synthesis of (–)‐[14C]homoharringtonine, for use in clinical studies, was achieved 17‐steps, starting from 14C‐labelled potassium cyanide.