Chemo-enzymatic synthesis of arginine-based gemini surfactants

A novel chemo-enzymatic synthesis of arginine-based gemini cationic surfact ants bis(Args) is reported. These compounds consist of two single N-alpha-a cyl-arginine structures connected through the alfa-carboxylic groups of the arginine residues by a alpha,omega-diaminoalkane spacer chain. N-alpha-Acy l-L-arginine alkyl ester derivatives were the starting building blocks for the synthesis. The best strategy found consisted of two steps: First, the q uantitative acylation of one amino group of the spacer by the carboxylic es ter of the N-alpha-acyl-arginine took place spontaneously, at the melting p oint of the alpha,omega-diaminoalkane, in a solvent-free system. The second step was the papain-catalyzed reaction between another N-alpha-acyl-argini ne alkyl ester and the free aliphatic amino group of the derivative formed in the first step. Reactions were carried out in solid-to-solid and solutio n systems using low-toxic potential solvents. Changes in reaction performan ce and product yield were studied for the following variables: organic solv ent, support for enzyme deposition and substrate concentration. The: best y ields (70%) were achieved in solid-to-solid systems and in ethanol at a(w) = 0.07. Bis(Args) analogs of 8, 10 and 12 carbon atoms using 1,3-diaminopro pane and 1,3-diamino-2-hydroxy-propane as hydrocarbon spacers were prepared at the 6-7 gram level employing the methodology developed. The overall yie lds which include reaction and purification varied from 51% to 65% of pure (97-98% by HPLC) product. (C) 2000 John Wiley & Sons, Inc.