Abstract:Anovel reagent, whichintroduces two sulfur atoms in one step,w as designed and used for the construction of diverse disulfanes by copper-catalyzed oxidative cross-coupling under mild reaction conditions.B ya pplying this stable and readily prepared reagent, late-stage modification of pharmaceuticals and natural products can be achieved straightforward. The scaled-up experiments further indicated the practicality of this protocol. The pH value of the system plays ak ey role in achieving highly selective cleavag… Show more
“…Two sulfur atoms were successfully introduced in one step via oxidative cross-couplings of acetyl masked disulfurating nucleophiles and organometallic reagents (Fig. 2b ) 52 . Fig.…”
From life science to material science, to pharmaceutical industry, and to food chemistry, polysulfides are vital structural scaffolds. However, there are limited synthetic methods for unsymmetrical polysulfides. Conventional strategies entail two pre-sulfurated cross-coupling substrates, R–S, with higher chances of side reactions due to the characteristic of sulfur. Herein, a library of broad-spectrum polysulfurating reagents, R–S–S–OMe, are designed and scalably synthesized, to which the R–S–S source can be directly introduced for late-stage modifications of biomolecules, natural products, and pharmaceuticals. Based on the hard and soft acids and bases principle, selective activation of sulfur-oxygen bond has been accomplished via utilizing proton and boride for efficient unsymmetrical polysulfuration. These polysulfurating reagents are highlighted with their outstanding multifunctional gram-scale transformations with various nucleophiles under mild conditions. A diversity of polysulfurated biomolecules, such as SS−(+)-δ-tocopherol, SS-sulfanilamide, SS-saccharides, SS-amino acids, and SSS-oligopeptides have been established for drug discovery and development.
“…Two sulfur atoms were successfully introduced in one step via oxidative cross-couplings of acetyl masked disulfurating nucleophiles and organometallic reagents (Fig. 2b ) 52 . Fig.…”
From life science to material science, to pharmaceutical industry, and to food chemistry, polysulfides are vital structural scaffolds. However, there are limited synthetic methods for unsymmetrical polysulfides. Conventional strategies entail two pre-sulfurated cross-coupling substrates, R–S, with higher chances of side reactions due to the characteristic of sulfur. Herein, a library of broad-spectrum polysulfurating reagents, R–S–S–OMe, are designed and scalably synthesized, to which the R–S–S source can be directly introduced for late-stage modifications of biomolecules, natural products, and pharmaceuticals. Based on the hard and soft acids and bases principle, selective activation of sulfur-oxygen bond has been accomplished via utilizing proton and boride for efficient unsymmetrical polysulfuration. These polysulfurating reagents are highlighted with their outstanding multifunctional gram-scale transformations with various nucleophiles under mild conditions. A diversity of polysulfurated biomolecules, such as SS−(+)-δ-tocopherol, SS-sulfanilamide, SS-saccharides, SS-amino acids, and SSS-oligopeptides have been established for drug discovery and development.
“…Disulfanes,animportant class of molecules containing asulfur-sulfur framework, which exists in nature, [1] have been widely employed in biochemistry, [2] food chemistry, [3] and the pharmaceutical industry, [4] as well as substrates for generating more complex sulfur-sulfur-containing molecules. [5] Among them, disulfane-bearing 2-aminofuran frameworks are particularly attractive since they are common structural motifs in many bioactive natural products and pharmaceutical entities [6] (Scheme 1). Forinstance,aspirochlorine (I or antibiotic A30641) is an ovel seven-membered epidithiapiperazine-2,5dione with distinctive antifungal properties resulting from selective inhibition of protein biosynthesis.I ts analogue tetrathioaspirochlorine (II)i ss lightly less potent in the antifungal assay according to the literature.…”
An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade. Remarkably, the Ts anion released from N-tosylhydrazone further serves as a nucleophile, thus rendering the formation of benzenesulfonothioates under controlled conditions.
“…From a practical and environmental perspective the use of the S-thiosulfonate is attractive because of the good manipulability and the avoiding of common drawbacks affecting sulfurating chemicals (odor, toxicity, instability). [16] It should be noted that the overall process was positively influenced by the basic conditions -due to the organolithium -of the mixture: by quenching the reaction with stoichiometric HCl (1 N) after realizing the homologation and, then adding the phenol, the full recovery of the αhalothioether 1 a was obtained (entry 13).…”
A conceptually intuitive synthesis of oxothioacetals is reported starting from thiosulfonates as electrophilic sulfur donors. The installation of a reactive CH 2 Cl motif with a homologating carbenoid reagent, followed by the immediate nucleophilic displacement with alcoholic groups [(hetero)-aromatic, aliphatic] offer a convenient access to the title compounds. Genuine chemoselectivity is uniformly observed in the case of multi-functionalized systems.
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