A method by which an intermediate product of an azole derivative can be produced at a lower cost than known production methods is provided. A method for producing a compound represented by General Formula (IV) includes converting a compound represented by General Formula (II) into the compound represented by General Formula (IV) using (a) dimethyl sulfide and/or dimethyl sulfoxide, and (b) a methyl-LG (an LG is a nucleophilically substitutable leaving group and is selected from the group consisting of a halogen group, an alkoxysulfonyloxy group, an aryloxysulfonyloxy group, an alkylsulfonyloxy group, a haloalkylsulfonyloxy group, and an arylsulfonyloxy group) in the presence of an inorganic base.

The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis/adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously “undruggable” oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.

The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis/adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously “undruggable” oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.

The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis/adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously “undruggable” oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

A process that allows halogenation at the alpha-H position of alkylarenes, optionally further substituted on the aromatic or heteroaromatic ring, is described.

A process that allows halogenation at the alpha-H position of alkylarenes, optionally further substituted on the aromatic or heteroaromatic ring, is described.

The present invention relates to the preparation of compounds of Formula I, including thapsigargin, nortrilobolide and 8-O-debutanoyl-thapsigargin from commercially available (R)-(−)-carvone via synthetic intermediate compound of formula 12 by pinacol coupling and in situ lactonization. ##STR00001##