A high-yield and simplified procedure for the synthesis of alpha-[C-11]methyl-L-tryptophan

Alpha [C-11]methyl-L-tryptophan (AMT) has been synthesized by stereoselective methylation with [C-11]methyl iodide of the lithium enolate generated by treating dimethyl 2(S),3a(R),8a(S)- (+)-hexahydro-8(phenylsulfonyl)pyrrolo[2,3-b] indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at -55 degrees C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 +/- 12% (decay corrected) in 30-35 min from [C-11]methyl iodide. At end of synthesis (EOS), 138 +/- 35 mCi (n = 24) of product was collected with a specific activity of ca. 1-1.3 Ci/mu mol (EOS) (4-5 Ci/mu mol @ EOB) starting from 1.5 Ci (EOB) of [C-11]CO2. Copyright (C) 1996 Elsevier Science Inc.