Glyoxalase I enzyme studies. 3. Synthesis and evaluation of .alpha.-hydroxythiol esters as antitumor agents and glyoxalase I inhibitors

Hall, Steven R.; Doweyko, Lidia M.; Doweyko, Arthur M.; Zilenovski, Judith S. Ryan

doi:10.1021/jm00220a002

Cited by 21 publications

(11 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3] These processes are facilitated due to the greater reactivity towards nucleophiles of thioesters compared to oxoesters, ascribed to the smaller orbital overlap between the sulfur atom and the carbonyl group in the former. Notwithstanding the usefulness of α-hydroxy or keto thioesters either as synthetic intermediates or in pharmaceutical products, [4] their widespread application has been hamstrung by the lack of a general method for synthesis.…”

Section: Introductionmentioning

confidence: 99%

Transition‐Metal‐Free Reduction of α‐Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent‐Controlled Chemoselectivities

Maity

Das

2019

Adv Synth Catal

View full text Add to dashboard Cite

The combination of hydrosilanes with a Brønsted or Lewis acid as a promoter can be used for the reagent-controlled chemoselective reduction at room temperature of conjugated C=C bond, enone moiety, or the carbonyl of (β,γ-unsaturated) α-keto thioesters, providing facile access to β,γ-saturated α-keto thioesters, αhydroxy thioesters, or silyl ethers. The reaction pathway and the chemoselectivity can be fine-tuned through the judicious choice of the hydrosilane or the reaction conditions. The reactions tolerate a wide range of functional groups including labile thioesters and the products are generally obtained in moderate to excellent yields. Unsymmetrical thioethers can also be synthesized using PMHS and catalytic B(C 6 F 5 ) 3 via reductive deoxygenation of both the carbonyl groups. The applicability has been highlighted by the amine-mediated and coupling reagent-free syntheses of saturated α-keto amides from β,γ-unsaturated α-hydroxy thioesters and β,γsaturated α-keto thioesters.

show abstract

Section: Introductionmentioning

confidence: 99%

Transition‐Metal‐Free Reduction of α‐Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent‐Controlled Chemoselectivities

Maity

Das

2019

Adv Synth Catal

View full text Add to dashboard Cite

show abstract

“…1154,1155 Additional attempts to create product mimetic inhibitors, based on α-hydroxythiol esters, were unsuccessful. 1156…”

Section: Lyases (Ec 4x)mentioning

confidence: 99%

Targeting Metalloenzymes for Therapeutic Intervention

et al. 2018

View full text Add to dashboard Cite

Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in disease and their importance as a class of targets has amplified interest in the development of new strategies to develop inhibitors and ultimately useful drugs. In this Review, we provide a broad overview of several drug discovery efforts focused on metalloenzymes and attempt to map out the current landscape of high-value metalloenzyme targets.

show abstract

“…In the end, we decided to try the Hall's method14 to synthesis S ‐MA‐CoA thioester indirectly. A series of α‐hydroxythiol esters were successfully prepared by this method.…”

Section: Discussionmentioning

confidence: 99%

“…S ‐MA‐CoA thioester was synthesized in a flask by the method of Stan S. Hall14 used for the synthesis of α‐hydroxythiol esters, with some modifications (Fig. 2).…”

Section: Methodsmentioning

confidence: 99%

Study on the metabolic mechanism of chiral inversion of S‐Mandelic acid in vitro

et al. 2011

View full text Add to dashboard Cite

Mandelic acid (MA) is generally used as a biological indicator of occupational exposure to styrene, which is classified as a class of hazardous environmental pollutants. It was found to undergo one-directional chiral inversion (S-MA to R-MA) in Wistar and Sprague-Dawley rats in vivo. This study was aimed to explore the metabolic mechanism of chiral inversion of S-MA in vitro. S-MA was converted to R-MA in rat hepatocytes, whereas MA enantiomers remained unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora. In addition, the synthesized S-MA-CoA thioester was rapidly racemized and hydrolyzed to R-MA by rat liver homogenate and S9, cytosolic and mitochondrial fractions. The data suggest that chiral inversion of S-MA may involve the hydrolysis of S-MA-CoA, and its metabolic mechanism could be the same as that of 2-arylpropionic acid (2-APA) drugs.

show abstract

Glyoxalase I enzyme studies. 3. Synthesis and evaluation of .alpha.-hydroxythiol esters as antitumor agents and glyoxalase I inhibitors

Cited by 21 publications

References 1 publication

Transition‐Metal‐Free Reduction of α‐Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent‐Controlled Chemoselectivities

Transition‐Metal‐Free Reduction of α‐Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent‐Controlled Chemoselectivities

Targeting Metalloenzymes for Therapeutic Intervention

Study on the metabolic mechanism of chiral inversion of S‐Mandelic acid in vitro

Contact Info

Product

Resources

About