The Tungsten-Promoted Synthesis of Piperidyl-Modified erythro -Methylphenidate Derivatives.
Jonathan D DabbsMegan N EricsonJustin H WildeRachel F LombardoEarl C AshcraftDiane A DickieW Dean HarmanPublished in: ACS central science (2023)
Due to its efficacy as a dopamine receptor agonist, methylphenidate (MPH) is of interest as a potential therapeutic for cocaine addiction. While numerous derivatives of MPH have been investigated for their potential medicinal value, functionalization of the piperidine ring has not been explored. The pyridine borane ligand in WTp(NO)(PMe 3 )(η 2 -pyBH 3 ) is dearomatized by the metal and can be elaborated to the analogous η 2 -mesylpyridinium complex. Installing a methyl phenylacetate moiety at the C2' position via a Reformatsky reaction followed by a tandem protonation/nucleophilic addition sequence results in a library of erythro MPH analogues functionalized at the piperidyl C5' position. The functional group is added chemoselectively to C5', cis to the methyl phenylacetate. Repeating this procedure with an enantioenriched source of the tungsten reagent results in enantioenriched MPH derivatives. All identities of the newly reported compounds are supported by comprehensive 2D NMR and HRMS data or crystallographic data.
Keyphrases
- structure activity relationship
- attention deficit hyperactivity disorder
- electronic health record
- big data
- magnetic resonance
- high resolution
- autism spectrum disorder
- molecular docking
- machine learning
- uric acid
- atomic force microscopy
- prefrontal cortex
- metabolic syndrome
- solid state
- artificial intelligence
- human health
- simultaneous determination
- molecularly imprinted
- solid phase extraction