Syntheses of radiolabeled ABT‐578 for ADME studies

Several isotopomers of ABT‐578 ( I , II , III , and IV ) were prepared starting from different labeled precursors: [5'‐³H]‐tetrazole ( 1 ), [5'‐¹⁴C]‐tetrazole ( 2 ), [40‐³H]rapamycin ( 3 ), and [2,11,31‐³H]rapamycin ( 4 ). It was shown that the tritium label at the 40 position of rapamycin is lost during an attempted synthesis of [40‐³H]ABT‐578 ( III ). Copyright © 2006 John Wiley & Sons, Ltd.