The radiosynthesis of nca [O-methyl-11C]viqualine, through an N-trityl-protected intermediate, as a potential pet radioligand for 5HT re-uptake sites
✍ Scribed by Claudio Pascali; Victor W. Pike; David R. Turton
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- French
- Weight
- 585 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
Viqualine, {4‐[3‐[3(R)‐ethenyl‐4(R)‐piperidinyl]propyl]‐6‐methoxyquinoline}, has been labelled in the O‐methyl position with no‐carrier‐added (nca) carbon‐11 (t~1/2~ = 20.4 min; β^+^ = 99.8%) to provide a potential radioligand for PET studies of 5HT re‐uptake sites. Direct treatment of desmethyl‐viqualine with nca [^11^C]iodomethane gave [O‐methyl‐^11^C]viqualine as only a minor product. NMR data suggested that the dominant product is that from the [^11^C]alkylation of the competing piperidino‐nitrogen. Protection of this nitrogen with the trityl group, followed by treatment with nca [^11^C]iodomethane in dimethyl sulphoxide with sodium hydroxide as base, and then rapid deprotection by mild acid hydrolysis gave nca [O‐methyl‐^11^C]viqualine as the main crude product (27% radiochemical yield, decay‐corrected from [^11^C]iodomethane). Radiochemically and chemically pure nca [O‐methyl‐^11^C]viqualine was obtained by work up on C18 Sep‐pak followed by reverse phase HPLC. The radiosynthesis, including final formulation for i.v. administration, takes 56 min after producing the carbon‐11 as [^11^C]carbon dioxide by the ^14^N(p,α)^11^C reaction. This radiosynthesis illustrates the potential utility of the trityl group for the protection of nitrogen in rapid carbon‐11 radiochemistry.