| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
The Pd(0)-mediated rapid coupling of methyl iodide with an excess of alkenyl tributylstannane was examined with the aim of incorporating a short-lived ^<11>C-labeled methyl group into a biologically significant organic compound with a 1-methylalkene unit for synthesis of a PET tracer. Four sets of reaction conditions designated A-D were established. These reactions performed in DMF at 60 ℃ for 5 min choose own favorable structures undergoing efficient cross-coupling. Reaction condition B, consisting of CH_3I/stannane/Pd_2(dba)_3/P(ο-tolyl)_3/CuCl/K_2CO_3 (1 : 40 : 0.5 : 4-6:2 : 5 molar ratio), works well in almost all cases. Condition D, consisting of CH_3I/stannane/Pd_2(dba)_3/P(ο-tolyl)_3/CuX (X = Br, Cl, or I)/CsF (1 : 40 : 0.5-5:2-20:2-20 : 5-50 molar ratio), shows the best results with regard to general applicability to tin substrates, affording the corresponding methylated product in >90% yield based on consumption of methyl iodide. The use of P(t-Bu)_2Me was less effective than P(ο-tolyl)_3, particularly for α,β-unsaturated carbonyl substrates. No regio- or stereoisomerization occurred under the established reaction conditions. The efficiency of the protocol was demonstrated by synthesis of an actual ^<11>C-methylated compound. This method provides a firm chemical basis for the synthesis of short-lived ^<11>CH_3-labeled PET tracers with a 1-methylalkene unit. Retinoids and their artificial derivatives are involved in important biological signal pathways as agonists targeting nuclear RAR/RXR receptors and the prototypical G protein-coupled receptor, rhodopsin. Squalene, a triterpenoid containing six isoprene units, is a major metabolite derived from mevalonic acid and is a key intermediate in the production of important bioactive steroids. PET study using the corresponding ^<11>C-labeled tracers would contribute to the possibility of in vivo biomolecular science.
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