100937-75-5Relevant articles and documents
Process for producing optically active (R)-tetrahydrothiophene-3-ol with high optical purity and high purity: Bioconversion and crystallization
Konuki, Kaname,Nagai, Hazuki,Ito, Masashi,Sameshima, Tomohiro
, p. 310 - 314 (2014)
(R)-Tetrahydrothiophene-3-ol (1) is a key intermediate in the synthesis of penem-based antibiotics. However, it is a viscous liquid at room temperature, which makes it impossible to purify the (R)-isomer especially in the presence of the (S)-isomer. In this study, we successfully developed a process for producing (R)-alcohol 1 with high optical purity by combining bioconversion and crystallization. (R)-Alcohol 1 was prepared by enantioselective bioreduction which used tetrahydrothiophene-3-one (2) as the substrate, and the optical purity was 70-92% ee. The (R)-alcohol 1 liquid was collected from incubation solution and purified to furnish (R)-alcohol 1 with 98.7% ee by cooling crystallization from organic solvents. The scale-up using common crystallization process was difficult, but we developed a crystallization process that employed a jacketed pressure filtration vessel equipped with an agitator which can be operated under low temperature from crystallization to filtration. This led to the establishment of a process for producing (R)-alcohol 1 with high optical purity, and the validity of this process was proved by the scale-up test.
Highly enantioselective reduction of a small heterocyclic ketone: Biocatalytic reduction of tetrahydrothiophene-3-one to the corresponding (R)-Alcohol
Liang, Jack,Mundorff, Emily,Voladri, Rama,Jennet, Stephan,Gilson, Lynne,Conway, Aaron,Krebber, Anke,Wong, John,Huisman, Gjalt,Truesdell, Susan,Lalonde, James
, p. 188 - 192 (2010)
By leveraging enzyme evolution technologies, the enantioselectivity of a KetoREDuctase (KRED) towards the nearly spatially symmetrical ketone tetrahydrothiophene-3-one was increased from 63% ee to 99.3% ee. The biocatalytic process gives (R)-tetrahy- drothiophene-3-ol in one step from a commodity chemical and supplants the original multistep hazardous processes starting from the chiral pool. The biocatalytic process has been successfully scaled to 100 kg.
Enantioselective reduction of heterocyclic ketones with low level of asymmetry using carrots
Machado, Naira Vieira,Omori, álvaro Takeo
, p. 475 - 480 (2021/09/27)
A whole spectrum of biocatalysts for asymmetric reduction of prochiral ketones is well known including the Daucus carota root. However, this type of reaction is still challenging when pro-chiral ketones present low level of asymmetry, like heterocyclic ketones. In this work, 4,5-dihydro-3(2H)-thiophenone (1), 2-methyltetrahydrofuran-3-one (2), N-Boc-3-pyrrolidinone (3), 1-Z-3-pyrrolidinone (4) and 1-benzyl-3-pyrrolidinone (5) were studied in order to obtain the respective enantioselective heterocyclic secondary alcohols. Except for 5, the corresponding alcohols were obtained in high values of conversion and with high selectivity. In order to circumvent the low isolated yield of the corresponding chiral alcohol from 2, we observed that the use of carrots in the absence of water is feasible. Addition of co-solvents was needed to the water-insoluble ketones 3 and 4. Comparatively, baker’s yeast was used for bio reductions of 1, 3 and 4. And in terms of conversion, selectivity and work-up, the use of carrots were a more efficient biocatalyst, as well as a viable method for obtaining 5-member heterocyclic secondary alcohols.
