AUTOMATED RADIOSYNTHESES OF [6-O-METHYL-C-11]DIPRENORPHINE AND [6-O-METHYL-C-11]BUPRENORPHINE FROM 3-O-TRITYL PROTECTED PRECURSORS

The antagonist [6-O-methyl-C-11]diprenorphine and the mixed agonist/antagonist [6-O-methyl-C-11]buprenorphine, radioligands for studying the opioid receptor system in vivo with positron emission tomography, were prepared by O-methylation of (3-O-trityl,6-desmethyl)diprenorphine and [3-O-trityl,6-desmethyl]buprenorphine, respectively, with [C-11]iodomethane. The use of the base-stable, acid labile trityl protecting group minimizes the formation of byproducts and allows reproducible radiosyntheses. The two-step syntheses were carried out in a fully automated system giving [6-O-methyl-C-11]diprenorphine in a 13-19% radiochemical yield with a sp. act. of 15.5-23.8 GBq mumol-1 at EOS. The preparation takes 45 min from EOB. Similarly, [6-O-methyl-C-11]buprenorphine is prepared in 50 min from EOB in 12.6-17% radiochemical yield, with a specific activity of 12.8-21.8 GBq mumol-1 at EOS. C-13 and H-1 NMR studies were used to characterize diprenorphine and buprenorphine derivatives and, in particular, to confirm the position of methylation.