Gearing Effects on -9-Anth-PyBidine-Cu(OAc)-Catalyzed Asymmetric Direct Haloimidation Reactions of Alkylidenemalononitriles.

A newly developed -9-anthranylmethyl bis(imidazolidine)pyridine (-9-Anth-PyBidine)-Cu(OAc) complex catalyzed asymmetric haloimidation reactions of alkylidenemalononitriles with -bromosuccinimide and -chlorosuccinimide, employing the succinimide moiety directly as a copper-bound nucleophile. The anthranyl substituent showed a gearing effect that produced a well-organized asymmetric sphere involving the -H proton of the imidazolidine ring in the ligand. The gearing effect afforded hydrogen bonding-assisted copper-catalyzed haloimidation reactions with high enantioselectivity.

Bis(imidazolidine)-Derived NCN Nickel-Pincer-Catalyzed Asymmetric Reactions.

A bis(imidazolidine)-derived NCN nickel-pincer complex (Bu-PhBidine-Ni-OTf: ) was synthesized by the oxidative addition of imidazolidine-containing aryl triflate to Ni(cod) in MeCN. exhibited asymmetric induction in three reactions. In the Friedel-Crafts reaction of indoles with -Boc imines, 3-indolylmethanamine products were obtained in 79% yield with 99% ee.

Successful Identification of a Novel Therapeutic Compound for Hepatocellular Carcinoma Through Screening of ADAM9 Inhibitors.

Background/aim: MHC-class I-related chain A (MICA) functions as a ligand for natural killer group D, an activating receptor on natural killer (NK) cells, and its expression correlates with the carcinogenesis and progression of hepatocellular carcinoma (HCC). Although membranous MICA (mMICA) activates NK cells, soluble forms of MICA (sMICA), shed by cleaving enzymes, such as A disintegrin and metalloprotease (ADAM) 9, suppress NK cells. Therefore, the prevention of MICA shedding through the inhibition of ADAM9 has the potential to activate cancer immunity.

Asymmetric Friedel-Crafts-Type Reaction of 2-Vinylindoles to -Boc Imines Using a Chiral Imidazolidine-Containing NCN-Pincer Pd Catalyst.

A chiral imidazolidine-containing NCN-pincer Pd-OTf complex () promoted the asymmetric nucleophilic addition of unprotected 2-vinylindoles to -Boc imines in a Friedel-Crafts-type manner. The chiral (2-vinyl-1-indol-3-yl)methanamine products become nice platforms for constructing multiple ring systems.

Development of a novel light-up probe for detection of G-quadruplexes in stress granules.

G-quadruplexes (G4s) regulate various biological processes in cells. However, cellular imaging of dynamically forming G4s in biomolecular condensates using small molecules has been poorly investigated. Herein, we present a fluorescent light-up probe with the ability to selectively stabilize G4s and enhance fluorescence upon G4 binding.

Intermolecular Catalytic Asymmetric Iodoetherification of Unfunctionalized Alkenes.

A newly prepared trinuclear Zn-(,,)-aminoiminobinaphthoxide complex () catalyzed the first general intermolecular asymmetric iodoetherification of unfunctionalized alkenes. Using , the iodoetherification reaction of unfunctionalized alkenes with -nitrophenols proceeded smoothly to give the products with up to 92.5:7.

Enantio- and diastereoselective double Mannich reaction of malononitrile with N-Boc imines using quinine-derived bifunctional organoiodine catalyst.

A chiral quinine-derived organic base catalyst with halogen bond donor functionality was used to catalyze the asymmetric double Mannich reaction of malononitrile with N-Boc and N-Cbz imines to afford 1,3-diamines in excellent yields with high enantio- and diastereoselectivities. With 2.2 equiv.

A Hypervalent Cyclic Dibenzoiodolium Salt as a Halogen-Bond-Donor Catalyst for the [4+2] Cycloaddition of 2-Alkenylindoles.

A stable, hypervalent cyclic dibenzoiodolium salt acted as a strong halogen bonding (XB)-donor catalyst for [4+2] cycloaddition of 2-alkenylindoles, and not as an oxidizing agent. The cross-[4+2] cycloaddition of 2-vinylindoles with 2-alkenylindoles was catalyzed smoothly by the hypervalent cyclic dibenzoiodolium triflate catalyst to give the tetrahydrocarbazoles in up to 99 % yield with 17 : 1 diastereoselectivity. The hypervalent cyclic dibenzoiodolium salt was also applicable to the Povarov reaction of 2-vinylindole with N-p-methoxyphenyl (PMP) imine to give the indolyl-tetrahydroquinoline in 83 % yield.

Chiral -Symmetric Aminomethylbinaphthol as Synergistic Catalyst for Asymmetric Epoxidation of Alkylidenemalononitriles: Easy Access to Chiral Spirooxindoles.

Chiral -symmetric 3,3'-bis(()-2-naphthylethylaminomethyl)-()-binaphthol () functions as an efficient organocatalyst for the asymmetric epoxidation of various alkylidenemalononitriles. The spiro-epoxyoxindole products obtained from isatilidenemalononitriles were easily transformed to the corresponding chiral dihydroquinoxalinyl spirooxindoles.

Catalytic Asymmetric Iodoesterification of Simple Alkenes.

Catalytic asymmetric iodoesterification of simple alkenes was achieved using a dinuclear zinc-3,3'-(R,S,S)-bis(aminoimino)binaphthoxide (di-Zn) complex. For iodoesterification using p-methoxybenzoic acid, the N-iodonaphthalenimide (NIN)-I system was effective for producing iodoesters in a highly enantioselective manner. The synthetic utility of chiral iodo-p-methoxybenzoates was also demonstrated.

Catalytic Asymmetric Aza-Friedel-Crafts-Type Reaction of Indoles with Isatin-Derived -Cbz-Ketimines Using a Chiral Bis(Imidazolidine)-Containing NCN-Pincer Palladium Catalyst.

A chiral bis(imidazolidine)-containing NCN-pincer palladium complex (Bu-PhBidine-Pd-OTf) was an efficient catalyst for the aza-Friedel-Crafts-type reaction of 1H-indoles with isatin-derived Cbz-ketimines to give chiral 3-aminobisindole compounds having differently oxidized indole units with high enantioselectivities.

Catalytic Asymmetric Synthesis of Chiral Bis(indolyl)methanes Using a Ts-PyBidine-Nickel Complex.

A chiral tosyl-substituted bis(imidazolidine)pyridine Ts-PyBidine-nickel complex was an efficient catalyst for Friedel-Crafts reaction of indoles with methylene indolinones to give bisindolylmethane compounds having differently oxidized indole units with high enantioselectivities. Alkylation of the products proceeded smoothly in a highly diastereoselective manner, providing an all-carbon quaternary carbon center without significant loss of enantiomeric excess.

Chiral Benzazaborole-Catalyzed Regioselective Sulfonylation of Unprotected Carbohydrate Derivatives.

Chiral benzazaborole-catalyzed regioselective sulfonylations of unprotected carbohydrate derivatives have been developed. This methodology enables direct regioselective functionalization of the secondary OH group in carbohydrate in the presence of the primary OH group. By using the chiral organoboron catalysis, kinetic resolution of the carbohydrate derivatives was also achieved.

Catalysis Based on C-I⋅⋅⋅π Halogen Bonds: Electrophilic Activation of 2-Alkenylindoles by Cationic Halogen-Bond Donors for [4+2] Cycloadditions.

Homo- and cross-[4+2] cycloadditions of 2-alkenylindoles, catalyzed by cationic halogen-bond donors, were developed. Under mild reaction conditions, 3-indolyl-substituted tetrahydrocarbazole derivatives were obtained in good to excellent yields. Experimental and quantum calculation studies revealed that the electrophilic activation of 2-alkenylindoles was achieved by C-I⋅⋅⋅π halogen bonds.

Disulfide-Catalyzed Iodination of Electron-Rich Aromatic Compounds.

Herein, a disulfide-catalyzed electrophilic iodination of aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) has been developed. The disulfide activates DIH as a Lewis base to promote the iodination reaction in acetonitrile under mild conditions. This system is applicable to a wide range of electron-rich aromatic compounds, including acetanilide, anisole, imidazole, and pyrazole derivatives.

Chiral benzazaboroles as catalysts for enantioselective sulfonylation of cis-1,2-diols.

A newly developed benzazaborole smoothly catalyzed the enantioselective sulfonylation of cis-1,2-diols. Using a chiral benzazaborole/NMI co-catalyst system, various sulfonate esters were prepared in high yields with good enantioselectivities.

Association of Halogen Bonding and Hydrogen Bonding in Metal Acetate-Catalyzed Asymmetric Halolactonization.

Cooperative activation using halogen bonding and hydrogen bonding works in metal-catalyzed asymmetric halolactonization. The Zn(OAc)-3,3'-bis(aminoimino)binaphthoxide (tri-Zn) complex catalyzes both asymmetric iodolactonization and bromolactonization. Carboxylic acid substrates are converted to zinc carboxylates on the tri-Zn complex, and the N-halosuccinimide (N-bromosuccinimide [NBS] or N-iodosuccinimide [NIS]) is activated by hydrogen bonding with the diamine unit of chiral ligand.

A chiral organic base catalyst with halogen-bonding-donor functionality: asymmetric Mannich reactions of malononitrile with N-Boc aldimines and ketimines.

A chiral organic base catalyst with halogen-bonding-donor functionality has been developed. This quinidine-derived acid/base catalyst smoothly promoted the asymmetric Mannich reaction of malononitrile and various N-Boc imines with up to 98% ee. The cooperative interaction with both substrates was responsible for the high activity that allowed a reduction of the catalyst amount to 0.

Dinuclear PhosphoiminoBINOL-Pd Container for Malononitrile: Catalytic Asymmetric Double Mannich Reaction for Chiral 1,3-Diamine Synthesis.

A phosphoiminoBINOL ligand was designed to form a dinuclear metal complex that could hold a malononitrile molecule. The dinuclear bis(phosphoimino)binaphthoxy-Pd(OAc) complex catalyzed a double Mannich reaction of N-Boc-imines with malononitrile to give chiral 1,3-diamines with high enantioselectivity. The rational asymmetric catalyst, which smoothly introduces the first coupling product to the second coupling reaction while avoiding the reverse reaction, facilitates the over-reaction into a productive reaction process.

Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line.

Increases in the expression of prostaglandin E (PGE) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase.

Catalytic Asymmetric Synthesis of Chiral 2-Vinylindole Scaffolds by Friedel-Crafts Reaction.

A chiral bis(imidazolidine)pyridine (PyBidine)-Ni(OTf) complex smoothly catalyzed an asymmetric Friedel-Crafts reaction of 2-vinylindoles with nitroalkenes to give chiral indoles in a highly enantioselective manner while maintaining the 2-vinyl functionality. The chiral 2-vinylindoles offer unique chiral scaffolds for diverse transformations.

Catalytic Asymmetric Synthesis of 3-Indolyl Methanamines Using Unprotected Indoles and N-Boc Imines under Basic Conditions.

A chiral imidazolidine-containing NCN/Pd-OTf catalyst (C4) promoted the nucleophilic addition of unprotected indoles to N-Boc imines. Using sulfinyl amines as the N-Boc imine precursors, the combined use of C4 with K CO activated the NH indoles to give chiral 3-indolyl methanamines with up to 98 % ee. Compared with conventional acid-catalyzed Friedel-Crafts reactions, this reaction proceeds under mildly basic conditions and is advantageous for the use of acid-sensitive substrates.

PyBidine-Ni(OAc)-Catalyzed Michael/Aldol Reaction of Methyleneindolinones and Thiosalicylaldehydes for Stereochemically Divergent Thiochromanyl-spirooxindoles.

(S,S)-Diphenylethylenediamine-derived bis(imidazolidine)pyridine (PyBidine)-Ni(OAc) complex catalyzed the asymmetric Michael/aldol reaction of methyleneindolinone and thiosalicylaldehyde to produce (2'R,3S,4'R)-thiochromanyl-spirooxindole having three contiguous stereogenic centers.

Asymmetric Hydrogenation of Unprotected Indoles Catalyzed by η(6)-Arene/N-Me-sulfonyldiamine-Ru(II) Complexes.

Protecting-group-free transformation is a challenging and important issue in atom-economical organic synthesis. The η(6)-arene/N-Me-sulfonyldiamine-Ru(II)-BF4 complex-catalyzed asymmetric hydrogenation of 2-substituted unprotected indoles in weakly acidic hexafluoroisopropanol gives optically active indoline compounds with up to >99% ee. Under mild reaction media, halogen atoms and synthetically important protecting groups (e.

Catalytic asymmetric [3 + 2]-cycloaddition for stereodivergent synthesis of chiral indolyl-pyrrolidines.

The stereochemical divergent synthesis of indolyl-pyrrolidines was accomplished using an imidazoline-aminophenol (IAP)-Ni(OAc)2 complex and a bis(imidazolidine)pyridine (PyBidine)-Cu(OTf)2 complex. The former catalyzed exo'-selective asymmetric [3 + 2] cyclization of iminoesters with indolyl nitroalkenes, and the latter catalyzed the reaction in an endo-selective manner. These catalysts are tolerant toward highly functional substrates that supply chiral indolyl-pyrrolidine hybrids.