Synthesis of ( S)-and ( R)- Harmicine from Proline: An Approach Toward Tetrahydro- β- carbolines

(S)- and (R)-Harmicine were synthesized from L- and D-proline, respectively. This chiral pool synthesis constitutes a new approach towards C1 substituted tetrahydro--carbolines. The developed route makes use of the 9-phenyl-9-fluorenyl protecting group strategy of amino acids to prevent racemization of the vulnerable -amino carbonyl stereocenter. Enantiopure harmicine (> 99%ee) was obtained in nine steps from commercially available starting material. The synthesis was performed without the use of any silica gel flash chromatography.