J. Appl. Cryst.の発刊に際して

The prevalence of isocoumarins in numerous natural products that exhibit a wide range of biological activities has generated a continued and enormous interest among synthetic and medicinal chemists. The isocoumarin framework represents one of the privileged structures for the development of natural product-inspired compounds of potential biological interest. Considerable efforts have been de- voted towards the synthesis of isocoumarins via either traditional or transition-metal catalyzed reactions. Among the metal catalyzed re- actions, the use of Cu, Pd, Ag, Ru, Rh or Ir salts/complexes for the construction of isocoumarin ring are noteworthy. Among the other methodologies, halo-lactonization emerged as a practical process. Apart from preparing a variety of isocoumarins and thienopyranones, synthesis of naturally occurring and bioactive isocoumarins have been carried out by using cutting edge technologies. This review article will briefly cover all these aspects along with the synthetic utility of isocoumarins, highlighting recent developments.

Isocoumarin and Its Derivatives: An Overview on their Synthesis and Applications

Cp*Ir(III) complexes have been shown to catalyze the oxidative coupling of benzoic acids with alkynes in methanol at 60 °C to form a variety of isocoumarins. The use of AgOAc as an oxidant was required to facilitate significant product formation. Alkyl alkynes were shown to be more reactive substrates than aryl alkynes, and a number of functional groups were tolerated on benzoic acid. Combined mechanistic and computational studies (BP86) revealed that (1) C–H activation occurs via an acetate-assisted mechanism; (2) C–H activation is not turnover limiting; and (3) the oxidant oxidizes the reduced form of the catalyst via an Ir(I)–Ir(II)–Ir(III) sequence.

Cp*IrIII-Catalyzed Oxidative Coupling of Benzoic Acids with Alkynes

Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization.

The kibdelones A-C (1-3) and their isomeric metabolites (cf. isokibdelone C 4) are hexacyclic tetrahydroxanthone natural products recently isolated by Capon and coworkers from the rare Australian actinomycete Kibdelosporangium sp. (Figure 1).[1] An interesting property is the facile equilibration of kibdelones B 2, and C 3 to a mixture of 1-3via keto/enol tautomerizations followed by quinone/hydroquinone redox reactions.[1] Related natural products include simaomicin α 5 which has been shown to sensitize cancer cells to cytotoxic agents including bleomycin at nanomolar concentrations and to exhibit potent antimalarial and anticoccidial activities. [2] Evaluation of the kibdelones in the NCI 60-cell panel of human cancer cell lines revealed that they are active at low nanomolar concentrations against a number of human tumor cell lines. For example, kibdelone A has a GI50 of 1.2 nm against a SR (leukemia) tumor cell line and <1 nm (GI50) against SN12C (renal) cell carcinoma.[1] In addition, the kibdelones were shown to display novel COMPARE analysis profiles for cancer cell growth inhibition.

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Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones

Synthesis and anti-inflammatory activity of fluorinated isocoumarins and 3,4-dihydroisocoumarins

Synthesis and anti-cancer, anti-metastatic evaluation of some new fluorinated isocoumarins and 3,4-dihydroisocoumarins

This is the first report showing that 3-(dichlorophenyl)isocoumarins and (±)-3,4-dihydroisocoumarins are plant and plant fungus growth inhibitors. 3-Dichlorophenylisocoumarins were synthesized by condensation of homophthalic acid with dichlorobenzoyl chlorides. The alkaline hydrolysis of these isocoumarins afforded keto acids. Racemic 3-(Dichlorophenyl)-3,4-dihydroisocoumarins were obtained by reduction of keto acids to racemic hydroxy acids, followed by cyclodehydration using acetic anhydride. The herbicidal, fungicidal and insecticidal activities of the synthesized compounds have been evaluated. Some of the synthesized compounds show excellent herbicidal and fungicidal activities but none of the synthesized compounds presented any insecticidal effects on the test insects. The findings of this study suggest that isocoumarins and related compounds may serve as lead compounds towards the design of bioactive herbicides and fungicides.

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Synthesis, herbicidal, fungicidal and insecticidal evaluation of 3-(dichlorophenyl)- isocoumarins and (±)-3-(dichlorophenyl)-3,4-dihydroisocoumarins

Dimethoxyhomophthalic acid is a key intermediate for the synthesis of highly biological active naturally and non-naturally occurring isocoumarins and 3,4-dihydroisocoumarins. It was synthesized efficiently in five steps from 3,5-dimethoxybenzaldehyde (1) via a series of reactions including synthesis of 3,5-dimethoxycinnamic acid (2) and 3-(3',5'-dimethoxyphenyl)propionic acid (3), cyclization of 3-(3',5'-dimethoxyphenyl)propionic acid (3) to 5,7-dimethoxy-1- indanone (4) and oxidative decomposition of methyl 2-hydroxy-2-(5,7-dimethyoxy-1-oxo-1H- inden-2(3H)-ylidene)acetate (5) to 3,5-dimethoxyhomophthalic acid (6). Natural isocoumarin, thunberginol B (3-(3',4'-dihydroxyphenyl)-6,8-dihydroxyisocoumarin) (10) was synthesized by the condensation of 3,5-dimethoxyhomophthalic acid (6) with 3,4-dimethoxybenzoic acid (7) followed by demethylation of intermediate (3-(3',4'-dimethoxyphenyl)-6,8- dimethoxyisocoumarin) (9). The synthesized compounds were purified by HPLC and characterized by elemental analysis, IR, 1 H NMR and mass spectrometry.

https://www.arkat-usa.org/get-file/23117/

A new total synthesis of natural isocoumarin, thunberginol B

C7H7BrN2O, monoclinic, P121/c1 (no 14), a = 12769(3) A, b = 12754(3) A, c = 5026(1) A, = 99874(4)°, V = 8065 A 3 , Z =4 ,Rgt(F) = 0028, wRref(F 2 ) = 0074, T = 293 K Source of material The title compound was synthesized by the reaction of ethyl ester of 2-bromobenzoic acid with hydrazine hydrate (80 %) in absolute ethanol The reaction mixture was refluxed for 7 h The excess of solvent was distilled off, the residue was filtered and washed with water Colorless thin needle-shaped single crystals suitable for Xray analysis were obtained by recrystallization from 60 % ethanol Experimental details While the H atoms bound to N atoms were refined freely due to their importance in hydrogen bonding, the H atoms attached to C atoms were refined using conventional restraints Discussion Aromatic hydrazides are a very important intermediate especially in the field of heterocyclic chemistry Aromatic hydrazide have been used for the synthesis of various biologically active five membered heterocycles such as 2,5-disubstituated-1,3,4oxadiazoles, 5-substituted-2-mercapto-1,3,4-oxadiazoles etc Due to its versatilities in the synthesis of various heterocyclic compounds, we have synthesized the title compound and report its structure The rms deviation from plane is 0678 A in the molecular structure of the title compound Within phenyl ring, the bond lengths lie between 1376(4) A and 1386(3) A highlighting the aromatic character The valence angle C2C1C6 of 1211(2)° is larger than the standard value (120°) The opening of this angle is due to the presence of the bromo group on C1, which involves a decrease of the ring angles on C1 (1182 (2)°) and C6 (1182(2)°) The C7O1 bond distance (1225(3) A) is compatible with respective distances in a related structure [2] and smaller than those usually observed in carboxylic acids (1365 A) The structure is influenced by quite interesting intra- and intermolecular hydrogen bonding which stabilizes the whole crystal structure

Ghulam Qadeer

Papers

Synthesis and anti-inflammatory activity of fluorinated isocoumarins and 3,4-dihydroisocoumarins

Synthesis and anti-cancer, anti-metastatic evaluation of some new fluorinated isocoumarins and 3,4-dihydroisocoumarins

Synthesis, herbicidal, fungicidal and insecticidal evaluation of 3-(dichlorophenyl)- isocoumarins and (±)-3-(dichlorophenyl)-3,4-dihydroisocoumarins

A new total synthesis of natural isocoumarin, thunberginol B

Crystal structure of 2-bromobenzoic acid hydrazide, C7H7BrN2O