Although the classical
enzymatic kinetic resolutions (EKRs) are
among the most important reactions in biocatalysis, the requirement
of application of chromatographic purification technique, which is
responsible for the generation of large amounts of waste organic solvents,
is its major drawback. To minimize the environmental impact of such
attempts and to address the current sustainability challenges, we
decided to develop a novel EKR methodology, which relies on the usage
of cheap, fully renewable, nontoxic, and irreversible acyl group donor
reagent, namely, α-angelica lactone.
The employed activated enol lactone-based acyl donor proved to be
a versatile reagent enabling efficient and highly enantioselective
(up to E ≫ 500) lipase-catalyzed resolution
of a set of racemic sec-alcohols with up to >99%
ee and near to quantitative isolation yields according to conversions
achieved during the respective EKR procedure. Moreover, α-angelica
lactone provided, in this case, an ability of fast and straightforward
separation of the enzymatic reactions’ products via chromatography-free
reactive liquid–liquid extraction (LLE) workup using either
saturated aqueous sodium bisulfate in dimethylformamide (DMF) or Girard’s
P reagent in a mixture of EtOH/AcOH (90:10, v/v), respectively. The
NaHSO3/DMF LLE workup and the subsequent reisolation of
the respective levulinate from the aqueous layer turned out to be
less efficient than a separation with Girard’s P reagent. The
selective LLE of optically active levulinate-Girard P-hydrazones from
the respective alcohols and further hydrolysis of the respective hydrazides
with diluted HClaq. could be performed with high levels
of recovery of both EKR products isolated usually without loss of
enantiomeric purity.