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Two visible-light-mediated O-H insertion protocols involving oximes and aryldiazoacetates leading to different products depending on the solvent employed are reported. In DCM, direct O-H insertion takes place. In THF, there is the additional incorporation of the ring-opened form of this solvent into the structure of the product. These metal-free protocols are mild and tolerant to air and moisture. The preparation of an acaricide has been developed as an example of synthetic application.

Histone deacetylase 6 (HDAC6) has become a promising therapeutic target for central nervous system diseases due to its more complex protein structure and biological functions. However, low brain penetration of reported HDAC6 inhibitors limits its clinical application in neurological disorders. Therefore, the benzazepine, a brain-penetrant rigid fragment, was utilized to design a series of selective HDAC6 inhibitors to improve brain bioavailability. Various synthetic strategies were applied to assemble the tetrahydro-benzazepine ring, and 22 compounds were synthesized. Among them, compound 5 showed low nanomolar potency and strong isozyme selectivity for the inhibition of HDAC6 (IC50 = 1.8 nM, 141-fold selectivity over HDAC1) with efficient binding patterns like coordination with the zinc ion and π-π stacking effect. Western blot results showed it could efficiently transport into SH-SY5Y cells and selectively enhance the acetylation level of α-tubulin with a moderate effect on Histone H3. Notably, pharmacokinetic studies demonstrated that compound 5 (brain/plasma ratio of 2.30) had an excellent ability to penetrate the blood-brain barrier of C57 mice. In male rats with transient middle cerebral artery occlusion (MCAO), compound 5 significantly reduced the cerebral infarction from 21.22% to 11.47% and alleviated neurobehavioral deficits in post-ischemic treatment, which provided a strong rationale for pursuing HDAC6-based therapies for ischemic stroke.

Photocages are light-sensitive chemical protecting groups that give investigators control over activation of biomolecules using targeted light irradiation. A compelling application of far-red/near-IR absorbing photocages is their potential for deep tissue activation of biomolecules and phototherapeutics. Toward this goal, we recently reported BODIPY photocages that absorb near-IR light. However, these photocages have reduced photorelease efficiencies compared to shorter-wavelength absorbing photocages, which has hindered their application. Because photochemistry is a zero-sum competition of rates, improvement of the quantum yield of a photoreaction can be achieved either by making the desired photoreaction more efficient or by hobbling competitive decay channels. This latter strategy of inhibiting unproductive decay channels was pursued to improve the release efficiency of long-wavelength absorbing BODIPY photocages by synthesizing structures that block access to unproductive singlet internal conversion conical intersections, which have recently been located for simple BODIPY structures from excited state dynamic simulations. This strategy led to the synthesis of new conformationally restrained boron-methylated BODIPY photocages that absorb light strongly around 700 nm. In the best case, a photocage was identified with an extinction coefficient of 124000 M-1 cm-1, a quantum yield of photorelease of 3.8%, and an overall quantum efficiency of 4650 M-1 cm-1 at 680 nm. This derivative has a quantum efficiency that is 50-fold higher than the best known BODIPY photocages absorbing >600 nm, validating the effectiveness of a strategy for designing efficient photoreactions by thwarting competitive excited state decay channels. Furthermore, 1,7-diaryl substitutions were found to improve the quantum yields of photorelease by excited state participation and blocking ion pair recombination by internal nucleophilic trapping. No cellular toxicity (trypan blue exclusion) was observed at 20 μM, and photoactivation was demonstrated in HeLa cells using red light.

This work reports a simple and efficient method for the direct phosphorylation of enamide under metal-free conditions. The P-centered radicals, derived from secondary phosphine oxides, are generated under mild reaction conditions in the presence of diphenyliodonium salt and Et3N and are introduced onto a range of enamides in good isolated yields. The method features broad substrate scope, good functional group tolerance, and efficient scale-up.

BINOL-based, chiral phosphoric acids catalyze the substitution of 1-(o-hydroxyphenyl)propargylic alcohols with enamides to furnish 7-alkynyl-12a-acetamido-substituted benzo[c]xanthenes and related heterocycles in a one-pot operation with excellent diastereo- and enantioselectivity. Ambient reaction temperature, operationally simple reaction conditions, low catalyst loading, high yields, and excellent stereocontrol are attractive features of this process and make it a highly practical and versatile transformation.

PROBLEM TO BE SOLVED: To prepare analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. SOLUTION: The present invention relates to an N6-substituted adenosine derivative and an N6-substituted adenine derivative selected from the group consisting of specific compounds. The present invention also relates to a pharmaceutical composition at least comprising a therapeutically effective amount of the compounds and a pharmaceutically acceptable carrier. The invention further relates to the compounds used in preparation of analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. COPYRIGHT: (C)2016,JPO&INPIT

Nitrimines are employed as powerful reagents for metal-free formal C(sp2)-C(sp2) cross-coupling reactions. The new chemical process is tolerant of a wide array of nitrimine and heterocyclic coupling partners giving rise to the corresponding di- or trisubstituted alkenes, typically in high yield and with high stereoselectivity. This method is ideal for the metal-free construction of heterocycle-containing drug targets, such as phenprocoumon.

A general and efficient method for the synthesis of benzo-fused 7- and 8-membered ring lactams via the Beckmann rearrangement of cyclic oximes is presented. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

The present invention provides N6-substituted adenosine derivatives and N6-substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.

Homogeneous Pd catalysts have been identified for the conversion of cyclohexenone and tetralone O-pivaloyl oximes to the corresponding primary anilines and 1-aminonaphthalenes. This method is inspired by the Semmler-Wolff reaction, a classic method that exhibits limited synthetic utility owing to its forcing conditions, narrow scope, and low product yields. The oxime N-O bond undergoes oxidative addition to Pd0(PCy3)2, and the product of this step has been characterized by X-ray crystallography and shown to undergo dehydrogenation to afford the aniline product.

The use of a BINOL-derived phosphate as a chiral anionic phase-transfer catalyst in a nonpolar solvent allows the enantioselective fluorination of enamides using Selectfluor as the fluorinating reagent. We demonstrate that a wide range of stable and synthetically versatile α-(fluoro)benzoylimines can be readily accessed with high enantioselectivity. These compounds have the potential to be readily elaborated into a range of highly stereodefined β-fluoroamines, compounds that constitute highly valuable building blocks of particular importance in the synthesis of pharmaceuticals.

The present invention provides N6-substituted adenosine derivatives and N6-substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.

1-Chloro-2-formyl indenes and tetralenes have been synthesized using Vilsmeier-Haack-Arnold reaction onto indanones and tetralones. Most of these analogues exhibited antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MICs ranging from 30 to 500 μg/mL. Analogue 13 was further modified to some derivatives. The most active analogue 23 showing MIC at 30 μg/mL was further evaluated for acute oral toxicity in Swiss albino mice and was found to be safe up to 300 mg/kg dose.

Disclosed are compounds of Formula (I) or stereoisomers or salts thereof, wherein: X1, X2, X3, W, Q1, Q2, and G2 are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The syntheses of some methoxy-substituted bicyclic lactams, of the types 3 and 4, are reported employing two different conditions for the Schmidt reaction of appropriate ketones and employing two different conditions for the Beckmann rearrangement of the corresponding ketoximes. The alkyl to aryl migration ratios of the reactions were determined by high-performance liquid chromatography analysis of the reactions. The mechanisms of the reactions reported are discussed, some limitations of the reported mechanisms identified, and an alternative mechanism proposed in light of the outcomes of the various reactions. Application of the Schmidt reaction and Beckmann rearrangement was used for the synthesis of some chloro bicyclic lactams, of the types 3 and 4. CSIRO 2010.

This invention provides a convenient method for converting oximes into enamides. The process does not require the use of metallic reagents. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines. The invention provides a process to convert a prochiral enamide into the corresponding chiral amide. In an exemplary process, a chiral amino center is introduced during hydrogenation through the use of a chiral hydrogenation catalyst. In selected embodiments, the invention provides methods of preparing amides and amines that include the 1,2,3,4-tetrahydro-N-alkyl-1-naphthalenamine or 1,2,3,4-tetrahydro-1-naphthalenamine substructure.

(Chemical Equation Presented) A facile and practical method for the synthesis of N-acetyl α-arylenamides has been developed from corresponding ketoximes as the starting materials with ferrous acetate as the reducing reagent. This methodology offers mild reaction conditions, simple purification procedures, and high yields for a variety of N-acetyl enamides.

A new direct coupling of cyclic enamides with aryl boronic acids via Pd(ii)-catalyzed C-H functionalization has been achieved with good yields (up to 90%).

Provided are an oxime compound represented by General Formula (1), a photosensitive composition containing the oxime compound as a photopolymerization initiator, a production method for a color filter using the photosensitive composition, and a color filt

A compound of formula (I): wherein: R1 and R2 together form a benzo ring optionally substituted by halogen or by alkyl, alkoxy, cyano, nitro, hydroxy, amino, alkylamino, dialkylamino or trifluoromethyl, and R3 and R4

A compound of formula (I): wherein: R1 and R2 together form a benzo ring optionally substituted by halogen or by alkyl, alkoxy, cyano, nitro, hydroxy, amino, alkylamino, dialkylamino or trifluoromethyl, and R3 represents h

PCT No. PCT/US95/15937 Sec. 371 Date Jun. 13, 1997 Sec. 102(e) Date Jun. 13, 1997 PCT Filed Dec. 7, 1995 PCT Pub. No. WO96/18602 PCT Pub. Date Jun. 20, 1996This invention relates to compounds of the formula: which are effective for inhibiting platelet agg

The quaternary salts of rigidized 1,3-oxazole compounds of the formula: STR1 where R is either H or CH3 O. The compounds are produced in a modif Robinson-Gabriel synthesis of oxazoles. These dyes are used in solution with non-interfering polar solvents, such as ethanol and H2 O, to form lasing media useful in dye lasers.

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