Organic Solvent-Tolerant Marine Microorganisms as Catalysts for Kinetic Resolution of Cyclic β-Hydroxy Ketones

Abstract

Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this report, we describe a straightforward approach to enantiomerically enriched (R)-and (S)-3-hydroxycyclopentanone 2a, (R)-and (S)-3-hydroxycyclohexanone 2b, and (R )-and (S )-3-hydroxycycloheptanone 2c involving a transesterification resolution of the racemates using whole cells of marine microorganisms as catalysts and vinyl acetate the acyl donor and solvent. Twenty-six strains from a wide collection of isolates from marine sediments were screened, and seven strains were found to markedly catalyze the resolution in an asymmetric fashion. Using the strain Serratia sp., (R)-2a was isolated in 27% yield with 92% ee and (S)-2a in 65% yield with 43% ee, corresponding to an Evalue of 37; (R)-2b was isolated in 25% yield with 91% ee and (S)-2b in 67% yield with 39% ee, corresponding to an E-value of 40; and (R)-2c was isolated in 30% yield with 96% ee and (S)-2c in 63% yield with 63% ee, corresponding to an E-value of 75.

The use of marine-derived fungi for preparation of enantiomerically pure alcohols

“…Continuing our longstanding interest in the application of marine fungi (Chen and Hanefeld 2013;Chen et al 2015), and in conjunction with our recent interest in the synthesis of optically pure chiral alcohols (Chen et al 2011(Chen et al , 2017Chen and Hanefeld 2013), in the present study, we became interested in the enantioselective reduction of prochiral aromatic ketones using marine-derived fungi, offering an alternative, highly enantioselective and minimally polluting route to important chiral alcohols. Here, we report the results of the evaluation of 13 fungi isolated from marine sources as promising biocatalysts for the enantioselective reduction of a variety of carbonyl compounds from various compound classes.…”

Applications of Marine-Derived Microorganisms and Their Enzymes in Biocatalysis and Biotransformation, the Underexplored Potentials

“…For example, cyclic β-hydroxy ketones were employed in a kinetic resolution by whole cells of 26 strains isolated from marine sediments. Seven bacterial strains presented enantioselectivity for ( R )- and ( S )-3-hydroxycyclopentanone, ( R )- and ( S )-3-hydroxycyclohexanone, and ( R )- and ( S )-3-hydroxycycloheptanone (Figure 2A) (Chen et al, 2017).…”

A Comparative Study on Asymmetric Reduction of Ketones Using the Growing and Resting Cells of Marine-Derived Fungi

“…To fully assess the potential of marine-derived fungi as biocatalysts for the enantioselective reduction of prochiral ketones, whole mycelia of 13 marine fungi ( Penicillium citrinum GIM 3.458, Penicillium citrinum GIM 3.251, Penicillium citrinum GIM 3.100, Aspergillus sclerotiorum AS 3.2578, Aspergillus sydowii AS 3.7839, Aspergillus sydowii AS 3.6412, Geotrichum candidum GIM 2.361, Geotrichum candidum GIM 2.616, Rhodotorula rubra GIM 2.31, Rhodotorula mucilaginosa GIM 2.157, Geotrichum candidum AS 2.1183, Geotrichum candidum AS 2.498 and Rhodotorula rubra AS 2.2241) were screened for stereoselective reduction of 1-(3-bromophenyl)ethan-1-one 1b . The screening reaction was initially performed with 10 mL of Na 2 HPO 4 -KH 2 PO 4 buffer (100 mM, pH 6.0) containing glucose (0.5 g), 5 mM 1-(3-bromophenyl)ethan-1-one ( 1b ), and 3 g of resting cells at 30 °C, due to its frequent use for described resting cell biotransformation [ 31 , 32 , 33 , 34 ]. The results are shown in Table 1 .…”