Enantioselektive Verseifungen substituierter, achiraler 3-Acyloxy-propylester mit Lipasen: Herstellung chiraler Derivate von „Tris(hydroxymethyl)methan”

Enantioselective Saponification of Substituted, Achiral 3-Acyloxy-propionates with Lipases: Synthesis of Chiral Derivatives of „Tris(hydroxymethyl)methane” Ethyl 3-hydroxy-2-(hydroxymethyl)propionate (11) was synthesized with an overall yield of 40% starting from the pentaerythritol derivative 5,5-bis(hydroxymethyl)-1,3-dioxane (7). Both OH groups of 11 were acylated (ethanoyl-, propanoyl-, butanoyl, hexanoyl, and octanoyl derivatives 6a—e), and the formed triesters were partially hydrolyzed by lipases. According to 19F-NMR analysis of the corresponding Mosher ersters, the monocapronate 12d formed by PPL (porcine pancreas lipase) showed an enantiomeric ratio of 93.5:6.5 (87% ee). Using standard reactions, it was converted into chiral non-racemic derivatives 16 (O-benzyl-O′-silyl) and 21 (O-benzyl-O′-methoxymethyl) of the C3v-symmetric title compound. Possible applications of these derivatives are discussed. A “model” for the enantioselectivity of PPL hydrolysis is formulated.