New efficient chiral derivatizing agent, alpha-cyano-alpha-fluoro(2-naphthyl)acetic acid (2-CFNA). application to the EE determination of (-)-3-acetoxy-2-fluoro-2-(hexadecyloxymethyl)propan-1-ol

The new chiral derivatizing agent (CDA), alpha-cyano-alpha-fluoro(2-naphthyl)-acetic acid (2-CFNA) 1 was prepared in optically pure form by chiral HPLC separation of racemic 2-CFNA methyl ester (2-CFNA Me ester) (+/-)-2. The ester was obtained by fluorination of methyl alpha-cyano(2-naphthyl)acetate with FClO3. 2-CFNA 1 has proven to be a significantly superior CDA for determination of enantiomeric excess (ee) of a primary alcohol when compared to alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA, Mosher's agent) and alpha-cyano-alpha-fluoro(p-tolyl)acetic acid (CFTA). The ee of (-)-3-acetoxy-2-fluoro-2-(hexadecyloxymethyl)propan-1-ol (-)-9, a fluorinated analog of anticancer active ether lipids, was determined using (+)-2-CFNA (+)-1.