Separation and HPLC Analysis of Diastereomers and Rotational Isomers of L‐N‐(Butyloxycarbonyl)‐3‐(3‐Hydroxyethyl‐4‐(Benzyloxy)‐Phenyl) Alanine Benzyl Ester

Abstract

We have synthesized intermediates towards the preparation of a dimeric derivative of L‐dopa for the potential treatment of Parkinson's disease. We synthesized L‐N‐(butyloxycarbonyl)‐3‐(3‐hydroxy‐ethyl‐4‐(benzyloxy)‐phenyl)alanine benzylester, a compound containing a secondary alcohol moiety that has a unique set of characteristics. Upon reduction of the precursor, which contained a ketone moiety, we synthesized a material that when formed, contained a pair of diastereomers of the secondary alcohol, each diastereomer also exhibiting two individually stable conformational isomers. We believe that the conformational isomers were generated by rotation of the C‐N bond of the BOC carbamate, and were so stable that they could be separated by normal phase HPLC techniques.

Energy optimization studies and molecular modeling techniques were performed using HyperChem, and rotational barrier energy values were calculated for the different conformational isomers for each of the diastereomers. HPLC and NMR techniques were also used to obtain information about these materials. Using the calculated data from these studies, and analyzing the HPLC chromatograms and NMR spectra we were able to fully determine the assignments for the diastereomers and the individual conformational isomers. We discovered that the SS form was synthesized preferentially over the SR form and, that in both cases. The E conformation was energetically more stable than the Z form.

Keywords:

• Diastereomers
• Rotational isomers
• HPLC
• Separation
• Dimer
• Levodopa