SYNTHESIS OF CYCLODOPA (LEUCODOPACHROM)

The synthesis of the methylester of cyclodopa (5.6‐dihydroxy‐indoline‐2‐carboxylic acid) is achieved by oxidative conversion of dopa methyl ester to dopachrome methyl ester and its subsequent reduction at pH 8, using respectively potassium hexacyanoferrate(III) and sodium dithionite. The efficiency of the oxidation step was found to be dependent on the rather low concentration of the reactants and the very short reaction time involved. After its production cyclodopa methyl ester was stabilized by immediate protonation followed by acetylation leading in a high yield to O,O,N‐triacetyl cyclodopa methyl ester. By partial hydrolysis this derivative gives an O,N‐diacetyl cyclodopa methyl ester and further N‐acetyl cyclodopa methyl ester. Cyclodopa methyl ester and cyclodopa are obtained by prolonged anaerobic hydrolysis. Micro‐separation procedures, nmr‐, uv‐spectra and chiral‐optical properties of cyclodopa and its derivatives are reported and discussed. It is shown by nmr evidence that under acidic conditions the aromatic proton on C(7) of cyclodopa slowly exchanges with deuterium. When an alcoholic solution of cyclodopa methyl ester and semicarbazide is allowed to oxidize in the air, the semicarbazone of dopachrome methyl ester forms. Copyright © 1968 Verlag GmbH & Co. KGaA, Weinheim