79107-71-4

Usage

Uses

Used in Flavor and Fragrance Industry:
3-Hydroxytetrahydrothiophene is used as a flavor and fragrance ingredient for its distinctive sulfur-like odor, enhancing the sensory experience of consumer products.
Used in Food Industry:
3-Hydroxytetrahydrothiophene is used as a flavor enhancer in foods such as soy products, cheese, and roasted nuts, where it contributes to the unique taste and aroma profiles of these products.
Used in Pharmaceutical Synthesis:
3-Hydroxytetrahydrothiophene is used as a building block in the synthesis of pharmaceuticals, playing a crucial role in the development of new drugs and therapeutic agents.
Used in Organic Chemical Synthesis:
3-Hydroxytetrahydrothiophene serves as a key intermediate in organic chemical synthesis, enabling the creation of a wide range of chemical compounds for various applications.
Used in Biological Research:
3-Hydroxytetrahydrothiophene is studied for its potential biological activities, including antimicrobial and anticancer properties, offering insights into new therapeutic approaches and applications in the field of medicine.

InChI:InChI=1S/C4H8OS/c5-4-1-2-6-3-4/h4-5H,1-3H2

Upstream product

• 1120-59-8 2,3-dihydrothiophene 
• 1003-04-9 Tetrahydrothiophen-3-one 
• 50-99-7 D-glucose 
• 138915-39-6 (R)-4-chloro-3-hydroxy-1-p-toluenesulfonyloxybutane 
• 147949-22-2 3(S)-(tetrahydropyranyloxy)tetrahydrothiophene 
• 61847-07-2 (S)-(+)-4-bromo-1,2-epoxybutane 
• 41241-10-5 (R)-<2<(Methanesulfonyl)oxy>ethyl>oxirane 
• 19398-47-1 1,4-dibromo-2-butanol 

Relevant academic research and scientific papers

Enantioselective reduction of heterocyclic ketones with low level of asymmetry using carrots

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.

Synthesis method of thiophanate side chain

The invention relates to a synthesis method of a thiophanate side chain, which comprises the following steps: using a material shown in the description as a raw material, using ketone reductase to reduce to produce a product shown in the description, and using monooxygenase to oxidize to produce a product shown in the description, after protection of para-tosyl, carrying out sulfonyl protection toobtain a target product shown in the description, according to the technical scheme, by using the ketone reductase and the monooxygenase, a first step of biotransformation and a second step of biotransformation are carried out respectively, the oxidation product in the second step is subjected to Ts (para-tosyl) protection, finally, sulfonyl protection is carried out to obtain the target product,because the first step and the second step are both biotransformation, extraction by using ethyl acetate is not needed, the use amount of the ethyl acetate is reduced.

Methodology Development in Directed Evolution: Exploring Options when Applying Triple-Code Saturation Mutagenesis

Directed evolution of stereo- or regioselective enzymes as catalysts in asymmetric transformations is of particular interest in organic synthesis. Upon evolving these biocatalysts, screening is the bottleneck. To beat the numbers problem most effectively, methods and strategies for building “small but smart” mutant libraries have been developed. Herein, we compared two different strategies regarding the application of triple-code saturation mutagenesis (TCSM) at multiresidue sites of the Thermoanaerobacter brockii alcohol dehydrogenase by using distinct reduced amino-acid alphabets. By using the synthetically difficult-to-reduce prochiral ketone tetrahydrofuran-3-one as a substrate, highly R- and S-selective variants were obtained (92–99 % ee) with minimal screening. The origin of stereoselectivity was provided by molecular dynamics analyses, which is discussed in terms of the Bürgi–Dunitz trajectory.

Catalytic Asymmetric Reduction of Difficult-to-Reduce Ketones: Triple-Code Saturation Mutagenesis of an Alcohol Dehydrogenase

Catalytic asymmetric reduction of prochiral ketones with the formation of enantio-pure secondary alcohols is of fundamental importance in organic chemistry, chiral man-made transition-metal catalysts, or organocatalysts and enzymes of the alcohol dehydrogenase (ADH) type. A distinct limitation is the traditional requirement that the α- and α′-moieties flanking the carbonyl function differ sterically and/or electronically. Difficult-to-reduce ketones such as tetrahydrofuran-3-one and tetrahydrothiofuran-3-one and related substrates are particularly challenging, irrespective of the catalyst type. The ADH from Thermoethanolicus brockii (TbSADH) is an attractive industrial biocatalyst, because of its high thermostability, but it also fails in the reduction of such ketones. We have successfully applied directed evolution using the previously developed concept of triple-code saturation mutagenesis at sites lining the TbSADH binding pocket with tetrahydrofuran-3-one serving as the model compound. Highly (R)- and (S)-selective variants were evolved (95%-99% ee) with minimal screening. These robust catalysts also proved to be effective in the asymmetric reduction of tetrahydrothiofuran-3-one and other challenging prochiral ketones as well. The chiral products, which are generally prepared by multistep routes, serve as synthons in the preparation of several important therapeutic drugs.

Origins of stereoselectivity in evolved ketoreductases

Mutants of Lactobacillus kefir short-chain alcohol dehydrogenase, used here as ketoreductases (KREDs), enantioselectively reduce the pharmaceutically relevant substrates 3-thiacyclopentanone and 3-oxacyclopentanone. These substrates differ by only the heteroatom (S or O) in the ring, but the KRED mutants reduce them with different enantioselectivities. Kinetic studies show that these enzymes are more efficient with 3-thiacyclopentanone than with 3-oxacyclopentanone. X-ray crystal structures of apo- and NADP+-bound selected mutants show that the substrate-binding loop conformational preferences are modified by these mutations. Quantum mechanical calculations and molecular dynamics (MD) simulations are used to investigate the mechanism of reduction by the enzyme. We have developed an MD-based method for studying the diastereomeric transition state complexes and rationalize different enantiomeric ratios. This method, which probes the stability of the catalytic arrangement within the theozyme, shows a correlation between the relative fractions of catalytically competent poses for the enantiomeric reductions and the experimental enantiomeric ratio. Some mutations, such as A94F and Y190F, induce conformational changes in the active site that enlarge the small binding pocket, facilitating accommodation of the larger S atom in this region and enhancing S-selectivity with 3-thiacyclopentanone. In contrast, in the E145S mutant and the final variant evolved for large-scale production of the intermediate for the antibiotic sulopenem, R-selectivity is promoted by shrinking the small binding pocket, thereby destabilizing the pro-S orientation.

Enantiomeric purity enrichment of (R)-tetrahydrothiophene-3-ol sulfonyl derivatives by crystallization

(R)-Tetrahydrothiophene-3-ol sulfonyl derivatives 3-19 were prepared by introduction of various sulfonyl groups at the hydroxyl group of (R)-tetrahydrothiophene-3-ol 1 with low enantiomeric purity (68-74% ee). Crystallization was applied to improve their

Process for producing optically active (R)-tetrahydrothiophene-3-ol with high optical purity and high purity: Bioconversion and crystallization

(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.

Ketoreductase polypeptides for the production of (R)-3-hydroxythiolane

The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize chiral compounds.

Ketoreductase polypeptides for the production of (R)-3-hydroxythiolane

The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize chiral compounds.

Highly enantioselective reduction of a small heterocyclic ketone: Biocatalytic reduction of tetrahydrothiophene-3-one to the corresponding (R)-Alcohol

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.