Abstract
A two-step stereoselective chemoenzymatic synthesis of optically active α-aryl-substituted oxygen heterocycles was developed, exploiting a whole-cell mediated asymmetric reduction of α-, β-, and γ-chloroalkyl arylketones followed by a stereospecific cyclization of the corresponding chlorohydrins into the target heterocycles. Among the various whole cells screened (baker’s yeast, Kluyveromyces marxianus CBS 6556, Saccharomyces cerevisiae CBS 7336, Lactobacillus reuteri DSM 20016), baker’s yeast was the one providing the best yields and the highest enantiomeric ratios (up to 95:5 er) in the bioreduction of the above ketones. The obtained optically active chlorohydrins could be almost quantitatively cyclized in a basic medium into the corresponding α-aryl-substituted cyclic ethers without any erosion of their enantiomeric integrity. In this respect, valuable, chiral non-racemic functionalized oxygen containing heterocycles (e.g., (S)-styrene oxide, (S)-2-phenyloxetane, (S)-2-phenyltetrahydrofuran), amenable to be further elaborated on, can be smoothly and successfully generated from their prochiral precursors.
Highlights
Oxygen-containing heterocycles are ubiquitous in natural products and biologically active compounds, and are very common in many blockbuster pharmaceuticals [1,2]
Findings, we describeperformance a chemoenzymatic synthetic to prepare opticallyon active we describe a chemoenzymatic synthetic strategy to strategy prepare optically active epoxides, oxetanes, and we describe a chemoenzymatic synthetic to prepare optically active epoxides, oxetanes, and tetrahydrofurans, which is based on the enantioselective bioreduction of α, β, and γ‐
Various microorganisms are known to express different alcohol dehydrogenases (ADHs), each one exhibiting a specific stereo-preference according to the species, the metabolic growth conditions
Summary
Oxygen-containing heterocycles are ubiquitous in natural products and biologically active compounds, and are very common in many blockbuster pharmaceuticals [1,2]. [5,6,7,8] because of their versatility related to the ring strain. Oxetane is present in Figure several1)natural organic of their versatility related to the ring strain. The oxetane skeleton is present in several natural organic natural organic products (e.g., oxetanocin, taxol, mitrophorone), and represents a versatile building products (e.g., oxetanocin, taxol, mitrophorone), and represents a versatile building block for the products (e.g., oxetanocin, mitrophorone), andEDO, represents block for the block for the construction oftaxol, biologically active (e.g., compounds (e.g., aEDO, 1), or other valuable construction of biologically active compounds Figure. It is [9,10,11]
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