Organic Solvent-Tolerant Marine Microorganisms as Catalysts
for Kinetic Resolution of Cyclic β-Hydroxy Ketones
Bi -Shuang Chen
Fayene Zeferino Ribeiro de Souza
Received: 3 November 2016 /Accepted: 3 May 2017 /Published online: 13 June 2017
Springer Science+Business Media New York 2017
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 syn-
thesis 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 resolu-
tion of the racemates using whole cells of marine microorgan-
isms 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 mark-
edly catalyze the resolution in an asymmetric fashion. Using the
strain Serratia sp., (R)-2a wasisolatedin27%yieldwith92%ee
and (S)-2a in 65% yield with 43% ee, corresponding to an E-
value of 37; (R)-2b wasisolatedin25%yieldwith91%ee and
(S)-2b in 67% yield with 39% ee, corresponding to an E-value of
40; and (R)-2c wasisolatedin30%yieldwith96%ee and (S)-2c
in 63% yield with 63% ee, corresponding to an E-value of 75.
Keywords Cyclic β-hydroxy ketones
Cyclic β-hydroxy ketones represent an important class of com-
pounds often found as valuable building blocks in the production
of natural products of biological interest (Hertweck 2009; Acetti
et al. 2010). Their simple structures belie challenging multi-step
syntheses, especially in the production of optically active variants
(Mestres 2004; Karmee and Hanefeld 2011a; Bisogno et al.
2009). Lipase-catalyzed kinetic resolution is a potentially useful
method for obtaining enantiopure compounds (de Miranda et al.
2015). This process presents a broad substrate scope with no
expensive cofactors, excellent stereoselectivity, environmentally
benign conditions, and organic solvent-tolerance, which has re-
sulted in its application in academic and industrial chemistry.
Indeed, many microbial-derived biocatalysts, including isolated
enzymes and whole cells, may serve as candidates for the kinetic
resolution of cyclic β-hydroxy ketones (Baxter et al. 2012;Busto
et al. 2010; Hsu et al. 2006; Kapoor and Gupta 2012;Shakeri
et al. 2010; Zhang et al. 2013). However, in a kinetic resolution
process, the ideal biocatalyst would only convert one enantiomer
to the product and leave the antipode mostly unreacted. The
preparation of the ideal biocatalyst, as well as the reaction itself,
should be simple and cheap.
In our previous work (Chen and Hanefeld 2013a;Karmee
et al. 2011b), we screened nine different isolated lipases (CAL-
A, CAL-B, CRL, PCL, Amano PSD-I, Pseudomonas stutzeri,
Alcaligenes sp., PFL, and pancreatic porcine lipase (PPL)) from
commercial sources for the kinetic resolutions of rac-3-
hydroxycylopentanone 2a and rac-3-hydroxycyclohexanone
2b and obtained enantiomerically enriched (R)-2a in 21% yield
and 83% ee, corresponding to an E-value (enantiomeric ratio) of
Electronic supplementary material The online version of this article
(doi:10.1007/s10126-017-9755-7) contains supplementary material,
which is available to authorized users.
* Bi -Shuang Chen
School of Marine Sciences, Sun Yat-Sen University,
Guangzhou 510275, Republic of China
Department of Biotechnology, Gebouw voor, Scheikunde, Delft
University of Technology, Delft, the Netherlands
Instituto de Química de São Carlos, Universidade de São Paulo, Sao
Mar Biotechnol (2017) 19:351–360