Regioselective acetylation of 7-deacetylforskolin with 11C-acetyl chloride

Article abstract of DOI:10.1002/(SICI)1099-1344(199604)38:4<337::AID-JLCR845>3.0.CO;2-Z

Reaction conditions were studied to control the acetylating position on 7-deacetylforskolin using [¹¹C]acetyl chloride. In a preliminary study using non-labeled acetyl chloride, pyridine, lutidine, triethylamine, N,N-diisopropylethylamine, dimethylaminopyridine (DMAP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were tested as the base in the acetylation. Pyridine was effective in selective acetylation to yield forskolin in any solvent, and DBU was effective for 1-acetyl-7-deacetylforskolin. Among toluene, dichloromethane and dichloroethane, toluene was the most suitable as the solvent for the selective acetylation of the 7-OH group to give forskolin with any base. In the selectivity of acetylation with [¹¹C]acetyl chloride, more [¹¹C]forskolin was obtained than [¹¹C]1-acetyl-7-deacetylforskolin (70:30) in the presence of pyridine in toluene. [¹¹C]1-acetyl-7-deacetylforskolin was preferentially synthesized with DBU in dichloromethane, and the ratio of [¹¹C]1-acetyl-7-deacetylforskolin to [¹¹C]forskolin was 98:2. For the yield of the [¹¹C]acetylated product, DBU in dichloromethane was also suitable to obtain [¹¹C]1-acetyl-7-deacetylforskolin. However, that of pyridine in toluene did not confer any advantages upon the yield of [¹¹C]forskolin compared with DMAP in toluene.