(195b) Design of Lipid Membrane Surfaces As Organocatalyst for Michael Reactions in Aqueous Media

L-proline is known to catalyze Michael addition reaction with enantioselectivity, whereas its catalytic activity is decreased by surrounding water. Herein, we developed the liposomes which can conduct Michael addition reaction of trans-β-nitrostyrene and acetone in aqueous media. In the case of L-Pro-catalyzed Michael addition, the membrane fluidity and polarity are major controlling factors for this reaction [1]. The highest conversion and rate constant of the reaction within the liposomes was achieved with the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-3-trimethylammoniumpropane (DPTAP) system. The catalytic activity of L-Pro in the liposome suspension was found to be comparable to that in a DMSO system. The reaction rate constant was found to be controlled by both the phase state of the liposome membrane and the surface charge on the membrane. Greater enantioselectivity was achieved in the presence of the liposomes than in DMSO solution, with corresponding enantiomeric excess values of 97.6% for the DOPC/DPTAP liposome system. Furthermore, the amphiphilic amine molecules (stearylamine)-modified liposomes also showed catalytic activities with enantioselectivity. The hydrophobic region of the liposome membrane, which is a relatively stable self-organizing system, can serve as an effective “platform” for molecular recognition and selective conversion in aqueous media.

[1] M. Hirose et al., Liposome Membrane as a Platform for the L-Pro-Catalyzed Michael Addition of trans-β-Nitrostyrene and Acetone. Langmuir, 2015, 31 (47), 12968–12974.