In order to obtain both enantiomers of aliphatic secondary alcohols via a greener method, the four-step resolution–separation process involving lipase-catalyzed enantioselective esterification and hydrolysis as well as two separation procedures both via heterogeneous azeotropic distillation was developed. (S)-2-Pentanol (ee = 98.6%), (R)-2-pentanol (ee >99%), (S)-2-octanol (ee = 98.2%), and (R)-2-octanol (ee = 98.5%) were all produced in high purity (>98%) and high yield (>90%). In addition to the two model substrates, this method could also be applied to the resolution of other aliphatic secondary alcohols.(−)-(R)-2-PentanolC5H12Oee >99% (GC)[α]D28.0=-20.1 (c 0.97, CHCl3)Source of chirality: enzymatic esterificationAbsolute configuration: (R)(−)-(R)-2-OctanolC8H18Oee = 98.5% (GC)[α]D28.3=-12.3 (c 0.98, CHCl3)Source of chirality: enzymatic esterificationAbsolute configuration: (R)

Candida rugosa lipase (CRL) is one of the most widely used lipases. To enhance the catalytic abilities of CRL in both aqueous and non-aqueous phases, hollow silica microspheres (HSMSs) with a pore size of 18.07 nm were used as an immobilization support, and aldehydecontaining dextrans were employed to further cross-link the adsorbed CRL. In the experimental ranges examined, the loading amount of lipase linearly increased to 171 ± 3.4 mgprotein/gsupport with the CRL concentration and all the adsorption equilibriums were reached within 30 min. After simple cross-linking, the tolerance to pH 4.0 ∼ 8.0 as well as the thermal stability of immobilized CRL at 40 ∼ 80°C were both substantially increased, and 82 ± 2.1% activity remaining after the sixth reuse. The immobilized CRL was successfully applied to the resolution of racemic ibuprofen in non-aqueous phase. The initial reaction rate increased by 1.4- and 3.6-fold compared with the rates of adsorbed and native lipases, respectively. Furthermore, the R-ibuprofen was obtained at ee > 93%, and the enantiomeric ratio reached E > 140 at the conversion of 50 ± 1.5% within 48 h.