title: Acetonide Protection of Dopamine for the Synthesis of Highly Pure N-docosahexaenoyldopamine.
abstract: Direct acetonide protection of the catechol of dopamine has proven to be problematic due to formation of Pictet-Spengler isoquinolines. Here we report an efficient method for acetonide protection of dopamine, allowing preparation of a dopamine prodrug without complications from the Pictet-Spengler reaction. Acetonide-protected dopamine was first synthesized by pre-protecting the amino group with phthaloyl followed by refluxing with 2,2-dimethoxypropane in the presence of TsOH. Further work demonstrated that Fmoc or trifluoroacetyl were also suitable N-protective groups, while Boc-protected dopamine gave an isoquinoline product. Acetonide-protected dopamine was coupled to DHA (all cis-4,7,10,13,16,19-docosahexaenoic acid) to produce the N-DHA-dopamine prodrug in high purity.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, US.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Bi-Huang
authors.initials: BH
authors.lastname: Hu
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Messersmith