Liposomes Can Achieve Enantioselective C–C Bond Formation of an α‑Amino Acid Derivative in Aqueous Media

• Published in: ACS omega Vol. 2; no. 1; pp. 91 - 97
• Main Authors: Iwasaki, Fumihiko, Suga, Keishi, Okamoto, Yukihiro, Umakoshi, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 31.01.2017
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.6b00479

We first report that a highly enantioselective C–C bond formation reaction was achieved with liposomes in aqueous media. Alkylation of N-(diphenylmethylene)­glycine tert-butyl ester (DMGBE) with benzyl bromide was conducted in the presence of cetyltrimethylammonium bromide micelles, resulting in a high conversion of DMGBE but little enantiomeric excess (e.e.) of the product. The same reaction was then carried out in 1,2-dioleoyl-sn-glycero-3-phosphocholine liposome suspensions, where the e.e. values were high (at least 90 % (S)), indicating that the liposome membranes can behave as the promoter of the enantioselective reaction. Changing the type of lipid to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine to form a more ordered bilayer membrane lowered the reaction conversion but still maintained high e.e.% , that is, >90 (S), regardless of lipid chirality. It is indicated that multiple interactions between the DMGBE intermediate and lipid molecules promoted the migration of the intermediate into the interior of the membrane, whose bottom side (Si face) could be free for alkylation. These results suggest that liposomes can promote and regulate the alkylation of amino acid derivatives.