The reaction of phenols or aryl ethers with tetronic acid mediated by BF3·OMe2 was investigated. This strategy allowed for the preparation of β-(hydroxyaryl)butenolides and β-arylbutenolides in a single step in a simpler way than previously reported synthetic methods
A catalytic asymmetric N-nitroso aldol reaction of alkenyl trifluoroacetates with nitrosoarenes was achieved using a DTBM-SEGPHOS·AgOTf complex as the chiral precatalyst and KHMDS as the base precatalyst in the presence of methanol. Optically active α-hydroxyamino ketones with up to 89% ee were regioselectively obtained in moderate to high yields not only from acyclic alkenyl esters but also from cyclic ones through the in situ generated chiral silver enolates.
We describe Pt(II)- and Fe(III)-catalyzed iminocarboxylations of oxime esters conjugated with 1,3-enyne and an ortho-alkynylarene moiety, followed by a spontaneous O→N acyl migration of the enol carboxylate intermediate to generate N-acyl pyrroles and isoindoles. The reaction scope for pyrrole synthesis is general, whereas the formation of isoindoles has a relatively narrow scope because of their instability.
A macrocyclic lactone strategy for the synthesis of 5E-isomer-free carboprost methyl ester was developed for the first time. The macrocyclic lactone being free of 5E-isomer can be easily prepared from modified Corey lactone. The key intermediate could be used as a building scaffold to prepare carboprost methyl ester and other prostaglandins effectively.
Here we report the synthesis of a novel reagent designed to prepare 2-amino-5-nitrothiazole (ANT) amides and analogues in high yields. N-(Trimethylsilyl)-2-amino-5-nitrothiazole (N-(TMS)-ANT) was prepared in 99% yield via silylation of ANT using 1,1,1,3,3,3-hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCl), and catalytic saccharin. N-(TMS)-ANT is a superb reagent for the preparation of ANT amides in excellent yields. Notably, cyclic anhydrides and base-sensitive acyl chlorides can be utilized with N-(TMS)-ANT to furnish ANT amides that are difficult to prepare by previously reported procedures.
Carbolithiation of (1-phenylvinyl)boronic acid pinacol ester with tert-butyllithium was used to generate α-phenylboryl carbanions that reacted in a straightforward manner with carbonyl groups through a boron–Wittig sequence. When unhindered α,β-unsaturated carbonyl compounds were used, 1,4-addition of the α-phenylboryl carbanions was observed over the boron–Wittig sequence.
A ZnI2-catalyzed addition of ammonium thiocyanate to olefins in the presence of 4-toluenesulfonic acid and tetrabutylammonium iodide has been developed. The reaction proceeds by a Markovnikov-type process and a radical isomerization, and gives the corresponding isothiocyanates selectively and in good yields.
A sustainable and atom-economic synthesis of the widely used rubber accelerator tetramethylthiuram monosulfide (TMTM) from tetramethylthiuram disulfide is reported. Triphenyl phosphite (TPPi) is employed as a green reductant to replace the usual sodium cyanide, which poses a severe safety risk due to its high toxicity. The new process proceeds smoothly under mild conditions with an excellent yield of TMTM. This single-step one-pot method also has the potential for producing the industrially important lubricant additive O,O,O-triphenyl thiophosphate as a high-added-value byproduct.
A practical method for the synthesis of hydroxyalkylated indolo[2,1-a]isoquinoline derivatives through the metal-free cascade cyclization of 2-arylindoles with alcohols in the presence of tert-butyl hydroperoxide (TBHP) is disclosed. The present method features transition-metal-free conditions and exceptional functional group tolerance. A series of valuable hydroxyalkylated indolo[2,1-a]isoquinoline derivatives bearing various functional groups is synthesized in moderate to excellent yields.
Malignant behavior and multiple abnormal cellular functions have rendered cancer a great challenge for scientists to treat. The rising death toll presents an alarming situation, and the side effects associated with marketed drugs has further increased the quest to develop new anticancer drug molecules. We herein report a rationally designed 2,4-disubstituted quinazoline-based bioactive pharmacophore possessing different substitution patterns to obtain potent anticancer active agents targeting tubulin polymerization. In this series, two compounds showed potent cytotoxicity against all four cancer cell lines (MCF-7, MD-MBA-231, A549, and HCT-116) comparable to that of colchicine. The compounds showed cell cycle arrest in the G2/M phase and induced apoptosis, which showed these compounds might act via binding to the colchicine binding site. These results were further confirmed via tubulin polymerization inhibition, which showed a similar profile to colchicine. Compounds with a propargyl moiety showed very low cytotoxicity as compared to colchicines, even in the presence of a trimethoxy substituent at the quinazoline ring, except for compound case. Two compounds are obtained as potential lead compounds for the development of active anticancer agents, with one having a similar profile to colchicine activity on tubulin polymerization inhibition. These compounds represent promising leads that deserve further investigation and optimization.