Efficient synthesis of enantiomerically pure thioester precursors of [C-11]McN-5652 from racemic McN-5652

An improved synthesis of the enantiomerically pure thioester precursors of [C-11](+)-McN-5652 ([C-11](+)-1), and [C-11](-)-McN5652 ([C-11](-)-1) start ing from racemic McN-5652 ((+/-)-1) is described. The Synthetic method incl udes the resolution of (+/-)-1 by:repeated crystallization of the (+)- and (-)-di-p-toluoyltartrates yielding (+)-McN-5652 ((+)-1) and (-)-McN-5652 (( -)-1), each with >98% enantiomeric purity. S-Demethylation of (+/-)-1, (+)- 1 and (-)-1, respectively was achieved by:treatment with sodium amide at lo w temperatures (-78 degrees C) followed by conversion of the intermediate t hiols 2 with acetyl chloride to give the corresponding thioester precursors (+/-)-3, (+)-3 oy:(-)-3. This demethylation method almost completely suppr essed the isomerization of the pharmacologically active trans diastereomer into the inactive cis form. Chiral HPLC analyses confirmed that the S-demet hylation proceeded without any racemization. C-11-labelling of(+)-3 or (-)- 3 yields :enantiomerically pure [C-11](+)-McN-5652 or [C-11](-)-McN5652, ea ch in 22 % radiochemical yield (decay-corrected, related to [C-11]CO2) and a specific radioactivity of 74 GBq/mu mol (2 Ci/mu mol) at the end of synth esis (EOS).