New radical methods for the potential synthesis of carbon‐13 and carbon‐14 labeled complex products

Abstract

The isotopic labeling of molecules for agrichemical and pharmaceutical uses is becoming more challenging as molecules become larger, involve more stereochemistry, and as intellectual property rights become more complex. As such, isotope chemists need to continually add new isotopic methods to their armamentarium to successfully label complex molecules with carbon-13 and carbon-14. Recently, there has been a surge in the use of radicals to form new carbon-carbon bonds and for the incorporation of functional groups which can be used to incorporate isotopically labeled carbons. This review will describe some potential new radical methods for incorporating isotopically labeled carbon into complex molecules or into substrates that can be attached to late stage intermediates to generate labeled products.

Late-Stage Isotopic Exchange of Primary Amines

“…Stable isotopes such as 2 H, 13 C, and 15 N have had important applications in elucidating chemical mechanisms − and in drug discovery as tracers for metabolic studies. − In addition, 13 C and 15 N -labeled amino acids have been extensively used as labeling tracers in quantitative proteomics (SILAC). , More specialized uses, such as in hyperpolarized NMR, are also emerging, increasing the demand for reliable syntheses of these labeled materials. As molecules for these advanced applications become more complex, new synthetic routes to prepare isotopically enriched materials must advance to minimize the length and cost of synthesis . Selective replacement of an atom for its isotope through late-stage functionalization is attractive because it obviates the need for a costly and time-consuming de novo synthesis.…”

“…As molecules for these advanced applications become more complex, new synthetic routes to prepare isotopically enriched materials must advance to minimize the length and cost of synthesis. 17 Selective replacement of an atom for its isotope through late-stage functionalization is attractive because it obviates the need for a costly and timeconsuming de novo synthesis. However, such a realization requires very mild reaction conditions and ideally complete isotopic exchange.…”