Chemoenzymatic enantioselective synthesis of 2-substituted glycerol derivatives

2-Substituted glycerol derivatives 4a–g were resolved by acylation with vinyl butyrate in the presence of lipases in organic media. The reverse reaction, the enzymatic hydrolysis of the corresponding butyrates 5a–g, was also highly stereoselective and provided the opposite enantiomers. High enantioselectivities (ee >90%) and good isolated yields were obtained for all substrates using the appropriate lipase. Pseudomonas cepacia lipase or the closely related Pseudomonas sp. lipase were the most efficient enzymes for the resolution of substrates bearing smaller aliphatic groups. Candida antarctica lipase B was more suitable as the biocatalyst in the resolution of more sterically demanding aromatic substrates. 2-Benzylglycerol derivatives were resolved in the presence of Rhizopus sp. lipase.

Figure optionsDownload as PowerPoint slide

(4S)-(2,2-Dimethyl-4-(prop-1-en-2-yl)-1,3-dioxolan-4-yl) methanolC9H16O3Ee ⩾ 98% (Chiral GC)[α]D22=-24.2 (c 1.09, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

[(4S)-4-(4-Fluorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl] methanolC12H15O3FEe = 96% (Chiral HPLC)[α]D22=-2.3 (c 2.57, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

[(4S)-4-Ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl butanoateC12H20O4Ee = 97% (Chiral GC)[α]D22=+31.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

[(4S)-2,2-Dimethyl-4-(prop-2-en-1-yl)-1,3-dioxolan-4-yl]methyl butanoateC13H22O4Ee = 99% (Chiral GC)[α]D22=-15.2 (c 1.05, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

[(4S)-2,2-Dimethyl-4-(prop-1-en-2-yl)-1,3-dioxolan-4-yl]methyl butanoateC13H22O4Ee ⩾ 98% (Chiral GC)[α]D22=+29.1 (c 1.30, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

[(4R)-2,2-Dimethyl-4-phenyl-1,3-dioxolan-4-yl]methyl butanoateC16H22O4Ee = 94% (Chiral HPLC)[α]D22=-18.7 (c 1.00, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

[(4R)-4-(4-Fluorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl butanoateC16H21O4FEe = 94% (Chiral HPLC)[α]D22=-17.9 (c 1.10, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

[(4S)-4-Benzyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl butanoateC17H24O4Ee = 94% (Chiral HPLC)[α]D22=-10.9 (c 1.00, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)