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 stereose lective methylation with [C-11]methyl iodide of the lithium enolate ge nerated by treating dimethyl 2(S),3a(R),8a(S)- (+)-hexahydro-8(phenyls ulfonyl)pyrrolo[2,3-b] indole-1,2-dicarboxylate (2) with lithium diiso propyl amide (LDA) at -55 degrees C, followed by ring opening using tr ifluoroacetic acid and alkaline hydrolysis of the protecting groups. T he crude product was purified by a simple reverse-phase C-18 Sep-Pak p rocedure. The purified product was isolated with an average radiochemi cal yield of 53 +/- 12% (decay corrected) in 30-35 min from [C-11]meth yl iodide. At end of synthesis (EOS), 138 +/- 35 mCi (n = 24) of produ ct 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. Copyri ght (C) 1996 Elsevier Science Inc.