A phenacrylate scaffold for tunable thiol activation and release

Abstract

A thiol-selective 2-methyl-3-phenacrylate scaffold with spatiotemporal control over delivery of a cargo is reported. The half-lives of decomposition could be tuned from 30 min to 1 day and the scaffold's utility in thiol-inducible fluorophore release in cell-free as well as within cells is demonstrated.

Esterase Activated Carbonyl Sulfide/Hydrogen Sulfide (H2S) Donors

“…Next, carbamothioates 2a, 2b, and 2c were synthesized from the corresponding 4-nitrophenolates 6a, 6b, and 6c, respectively by reaction with the thiol 4 (Table 1). 33 (4-((4-Nitrophenoxy)methyl)phenoxy)methyl pivalate 7 was prepared and used as a negative control. This compound should be cleaved by esterases but will not produce COS.…”

Chemoproteomics of an Indole-Based Quinone Epoxide Identifies Druggable Vulnerabilities in Vancomycin-Resistant Staphylococcus aureus

“…With IND-QE, the possibility of tuning the thiol reactivity with varying substituent size offers a unique and complementary approach for interrogating cysteines with a large range of p K a s. The precise rationale for preferential attack on one carbon of the epoxide ring over the other remains to be deciphered. However, to the best of our knowledge, this is the first report where tunability of reactivity with thiol using an epoxide warhead is achieved by modulation of sterics around the electrophile. − …”

“…However, to the best of our knowledge, this is the first report where tunability of reactivity with thiol using an epoxide warhead is achieved by modulation of sterics around the electrophile. 30−32…”

Polythioethers bearing side groups for efficient degradation by E1cB reaction: reaction design for polymerization and main-chain scission

“…Since the product 8c involved an S N 1′ mechanism, i.e. , the elimination–substitution mechanism, was considered reasonable rather than S N 1 and S N 2 reaction 25 toward 7c . In this context, the phenyl substituent might have a decisive effect on promoting the formation of 8c , as the resonance effect stabilizes the intermediate 12c .…”

“…Herein, the elimination from the phosphonium end of 3-III to the chain end 3-IV is possible. A basic catalyst, such as Et 3 N, that directly deprotonates thiols was also effective in promoting conjugate substitution, 25 and the weak base was expected to decrease the side reaction. Thus, Et 3 N (entry 4) and iPr 2 NEt (entry 5) were analysed but found ineffective in increasing the molecular weight, probably due to the low activity.…”