We have developed a simple procedure to synthesize halogenated tetrahydroisoquinolines, intended as substrates for precursor directed biosynthesis, from halogenated aromatic amino acids and dopamine in aqueous buffered media. The one-pot biomimetic scheme uses one equivalent of sodium hypochlorite to quantitatively convert halogenated tyrosine and phenylalanine analogs to aldehydes by oxidative decarboxylation in phosphate buffer. This step is followed by addition of dopamine to generate racemic norcoclaurine at high yield. The resulting tetrahydroisoquinoline compounds may be obtained in high purity by extraction. Alternatively, the reaction solution may be used directly as an additive to growth media for precursor-directed biosynthesis in plant cell culture. Finally, we demonstrate alternative conditions for one-pot synthesis of halogenated (S)-norcoclaurine analogs using recombinant norcoclaurine synthase enzyme instead of phosphate buffer as the catalyst for Pictet-Spengler condensation.

Facile and green synthesis of tetrahydroisoquinolines from amino acids via one-pot decarboxylation and Pictet-Spengler condensation

247th National Meeting (2014)

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