One-Pot, Direct Incorporation of [ C]CO2 into Carbamates

摘要

Positron emission tomography (PET) is a prevailing noninvasive research tool for the investigation of biochemical processes and the elucidation of molecular interactions relevant to human health. The enabling technology that underlies PET and other radiotracer imaging methods is radiotracer chemistry. Thus, the continued success of PET and the expansion of its potential relies on the development of methods to incorporate positron-emitting isotopes into compounds intended, for example, as biomarkers for human disease. Arguably, one of the most important isotopes for PET research is carbon-11 (t1/2 = 20.4 min) as a result of its ubiquity in pharmacologically active compounds and its favorable physical properties. However, only a limited number of reactions that meet the special demands and constraints of carbon-11 chemistry have been developed. Even fewer are routinely employed owing to process complexity and/or the requirement for special equipment. Recently, we have placed a focus on the development of chemical methods for carbon-11 labeling that can be easily and immediately implemented, and herein we describe a new method that addresses the carbamate functional group. Synthesis with carbon-11 begins with the use of a cyclotron that produces ~(11)CO2 or ~(11)CH4 via a nuclear reaction (typically, [~(14)N(p,alpha)~(11)C]). In most cases, this "starting material" must be converted rapidly into a more useful reagent, for example, ~(11)CH3I, which is then used to label a precursor compound. The process of reagent synthesis alone can consume more than half of the radioactivity (if one considers decay during reaction time x yield of eachconversion step x trapping efficiency). In this respect, chemical reactions in which ~(11)CO2 or ~(11)CH4 is used directly have a clear advantage in terms of radiochemical yield. If properly designed, direct incorporation strategies can eliminate or reduce the need for special equipment.