Synthesis of Resorcinols via a Michael Addition-Dieckman Cyclization Sequence of Dimethyl 1,3-Acetonedicarboxylate Anion with Alkyl Alkynoates

The reaction of dimethyl 1,3-acetonedicarboxylate anion 1 with a number of alkyl alkynoates gives unsymmetrical (from alkynoates 2a-g) or symmetrical (from alkynoates 2h-i) resorcinols, in a one pot synthesis.     

Bifunctional hydrogen-bond donors that bear a quinazoline or benzothiadiazine skeleton for asymmetric organocatalysis

Hydrogen-bond (HB)-donor catalysts that bear a 2-aminoquinazolin-4-(1H)-one or a 3-aminobenzothiadiazine-1,1-dioxide skeleton have been developed, and it has been shown that these catalyst motifs act similarly to other HB-donor catalysts such as thioureas. The highly enantioselective hydrazination of 1,3-dicarbonyl compounds was realized even at room temperature with up to 96% ee for 2-aminoquinazolin-4-(1H)-one-type catalysts, which were more effective than the corresponding urea and thiourea catalysts. In addition, benzothiadiazine-1,1-dioxide-type catalysts were shown to promote the isomerization of alkynoates to allenoates with high enantioselectivity. To overcome the problem that the products were obtained as mixtures with the starting alkynoates, we developed the tandem isomerization and cycloaddition of alkynoates for the synthesis of advanced chiral compounds such as bicyclo[2.2.1]heptenes and 3-alkylidene pyrrolidine without a significant loss of enantioselectivity.     

Et3N-promoted tandem ring-opening reaction of N-tosylaziridines with terminal alkynoates: a straightforward synthesis of functionalized enamines

A tandem ring-opening reaction of N-tosylaziridines with terminal alkynoates promoted by Et(3)N has been described. A variety of N-tosylaziridines reacted with terminal alkynoates to give functionalized enamines in moderate to good yields under simple reaction conditions.     

Dual reactivity pattern of allenolates "on water": the chemical basis for efficient allenolate-driven organocatalytic systems

A study of the reactivity pattern associated with zwitterionic allenolates "on water" is reported. This study establishes the chemical basis for two organocatalyzed allenolate-driven reaction networks operating "on water". The first one is a chemodifferentiating three building block (ABB') three-component reaction (ABB' 3CR) manifold comprising terminal alkynoates and aldehydes. The manifold produces propargylic enol ethers 3 with higher average efficiency than their homologues in organic solvents. The second one is a novel organocatalytic system elicited by the reaction of alkynoates and nitrones in the presence of tertiary amines or phosphines. While terminal alkynoates afford 2,3,5-trisubstituted 2,3-dihydroisoxazoles 5 and propargylic N-hydroxylamines 6, internal alkynoates selectively afford the 2,3,4,5-tetrasusbstituted 2,3-dihydroisoxazaole 10. Importantly, in both cases, the 2,3-dihydroisoxazole ring is obtained as a sole regioisomer.     

Cu-catalyzed stereoselective conjugate addition of arylboronic acids to alkynoates

The CuOAc-catalyzed reaction of internal alkynoates with arylboronic acids proceeded under mild conditions to yield trisubstituted cinnamates stereoselectively.     

Rhodium(III)‐Catalyzed Tandem [2+2+2] Annulation–Lactamization of Anilides with Two Alkynoates via Cleavage of Two Adjacent C−H or C−H/C−O bonds

An electron‐deficient Cp^E rhodium(III) complex bearing a cyclopentadienyl ligand with two ethyl ester substituents catalyzes the tandem [2+2+2] annulation–lactamization of acetanilides with two alkynoates via cleavage of adjacent two C?H bonds to give densely substituted benzo[cd]indolones. The reactions of meta‐methoxy‐substituted acetanilides with two alkynoates also provided benzo[cd]indolones via cleavage of adjacent C?H/C?O bonds. Furthermore, 3,5‐dimethoxyacetanilides reacted with two alkynoates to give dearomatized spiro compounds.     

Organocatalysis "on water". Regioselective [3 + 2]-cycloaddition of nitrones and allenolates

The first example of a regioselective and organocatalyzed 1,3-dipolar cycloaddition reaction between conjugated alkynoates and nitrones "on water" is described.     

Synthesis of N4-(5-methoxy-7-benzofuranyl)-1,4-pentanediamine,an oxygen isostere of primaquine

N⁴-(5-Methoxy-7-benzofuranyl)-1,4-pentanediamine, an oxygen isostere of primaquine was synthesized and found devoid of antimalarial activity.     

Benzofurans and sterol from the seeds of <Emphasis Type="Italic">styrax obassia</Emphasis>

Two benzofurans (1, 2) along with five known compounds (3.7) were isolated from the seeds of S. obassia. Their structures were elucidated as methyl 3-[7-methoxy-2-(3′,4′-methylenedioxyphenyl)-5-benzofuranyl]-propionate (1), methyl 3-[2-(3′,4′-methylenedioxyphenyl)-5-benzofuranyl]-propionate (2), egonol (3), egonolacetate (4), egonol-2-methylbutanoate (5), 7-demethoxyegonol-2-methylbutanoate (6), and stigmasterol (7) on the basis of their comprehensive spectroscopic analysis including 2D NMR data. Compounds 1, 2 are obtained for the first time from nature, while this is the first record of compound 7 from the Styrax species. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 350-353, July-August, 2008. Original article submitted May 4, 2007.     

Determination of the new monoamine oxidase inhibitor brofaromine and its major metabolite in biological material by gas chromatography with electron-capture detection

A sensitive gas chromatographic assay for the simultaneous determination of brofaromine [4-(7-bromo-5-methoxy-2-benzofuranyl)piperidine hydrochloride], a new monoamine oxidase-A inhibitor, and its major metabolite was developed and validated. After addition of 4-(5-bromo-2-benzofuranyl)piperidine as internal standard, the compounds were isolated from biological fluids by liquid-liquid extraction at basic pH. After derivatization with heptafluorobutyric anhydride the compounds were chromatographed using a packed column (OV-17) and an electron-capture detector. The limit of quantitation was ca. 0.03 nmol per sample (10 ng) for both compounds. analysis of spiked samples demonstrated the good accuracy and precision of the method, which is suitable for use in pharmacokinetic and bioavailability studies. The method was applied to samples from an experiment in a healthy volunteer treated with a single oral dose of 75 mg of brofaromine hydrochloride. Plasma profiles before and after enzymic hydrolysis showed that about one-third of the total brofaromine in plasma and practically all of the major metabolite (O-desmethylbrofaromine) were present in the conjugated form.     

A Convenient Oxidation of 5‐Substituted Pyrazol‐3(2H)‐Ones Into Methyl 2‐Alkynoates Using Poly[4‐(Diacetoxyiodo)Styrene]

An operationally simple oxidation of 5‐substituted pyrazol‐3(2H)‐ones to the corresponding methyl‐2‐alkynoates in good yields with a mediated poly[4‐(diacetoxyiodo)styrene] system in methanol and acetonitrile at room temperature was carried out. The polymeric reagent can be regenerated and reused as an environmentally benign reagent.     

Radical reactions of aryl alkynoates in organic synthesis: Recent advances

Aryl alkynoate is an important intermediate and powerful synthetic tool in organic chemistry, because it contains acetylene bond which can be easily introduced of different functional groups. During the past decades, several types of reactions and coupling partners have been developed for the functionalization of aryl alkynoates. In this review, we summarize the recent advances on the reactions of aryl alkynoates, including direct cyclization, ester group migration/cyclization, aryl migration/decarboxylation, ipsocyclization/dearomatization, and other reactions in the past decade.     

Benzofuran systems. Synthesis and biological examination of 1-(3-benzofuranyl)-2-phenylethanones

Novel 1-(3-benzofuranyl)-2-phcnylethanones 4a-d have been prepared by acetylation of 2-alkylbenzo-furans 2a-c with phenylacetyl chlorides 3a-b . The methoxy derivatives 4b-d have been demethylated to the corresponding phenols 5b-d with pyridinium hydrochloride. An attempt to obtain the derivatives of 4d and 5a iodinated in the phenyl ring has been undertaken. The novel compounds have been characterized by ir and nmr spectra and their biological activity examined.     

Synthesis of Bis(2-benzofuranyl) Diselenides from 4-(2-Hydroxyaryl)-1,2,3-selenadiazoles

4-(2-Hydroxyaryl)-1,2,3-selenadiazoles obtained by the action of selenium(IV) oxide on o-hydroxyacetophenone semicarbazones are readily converted into the corresponding potassium benzofuran- 2-selenolates via reaction with potassium carbonate. Oxidation of potassium benzofuran-2-selenolates with iodine gives bis(2-benzofuranyl) diselenides in good yields.     

Chemo-differentiating MCRs based on alpha-ketoesters and terminal alkynoates. A homoaldol-based ABB' system

A novel ABB' 3 component reaction (3-CR) system based on the organocatalyzed homoaldolic condensation of alpha-ketoesters in the presence of terminal conjugated alkynoates is described.     

Silver-catalyzed highly efficient synthesis of pyrido[1,2-a]pyrimidin-4-ones from 2-aminopyridines and alkynoates

Pyrimidinone is one of the important nitrogen containing heterocycles due to their wide range of bioactivities. An efficient silver-catalyzed intermolecular cyclization of 2-aminopyridines with various alkynoates has been developed. 2-Substituted 4H-pyrido[1,2-a]pyrimidin-4-ones containing a wide range of functional groups are synthesized in the standard conditions. This transformation is conducted under convenient conditions and affords products in good yields.     

用烯炔偶联环化合成具有生物活性内酯

最近, 我们发展了一个用两价钯催化开链烯丙基炔酸酯环化以立体选择性合成α-亚烷基-γ-丁内酯的方法[1]。在此法中, γ-丁内酯环是由原料酯中的烯炔环化发生碳-碳键偶联而生成的。值得注意的是: 反应产物中β, γ-位取代基的立体化学可以由叁键上的取代情况来控制, 即无取代的丙炔酸酯生成β,γ-反式二取代产物, 而取代的炔酸酯生成β, γ-顺式二取代产物。此方法特别意义在于可从易得的光学纯烯丙醇出发合成具有生物活性的光学纯内酯的任何一个对映体[2]。     

Some reactions of 4-[(2′,3′-diphenyl-6′-methoxy-5′-benzofuranyl)-methylene]- and 4-[(2′,3′-diphenyl-5′-methoxy-6′-benzofuranyl)-methylene]-2-phenyloxazolin-5-one

2,3-Diphenyl-5-formyl-6-methoxybenzofuran was reacted with hippuric acid to give 4-[(2′,3′-diphenyl-6′-methoxy-5′-benzofuranyl)methylene]-2-phenyloxazolin-5-one. The above mentioned oxazolone yielded 2,3-diphenyl-6-methoxybenzofuranylacetic acid by reaction with hydrazine hydrate, nitrous acid, benzene followed by acid hydrolysis. The reactions of the oxazolone with hydroxylamine hydrochloride and primary or secondary amines were also investigated.     

Metal-free access to fully substituted skipped diynes. An efficient chemodifferentiating A2BB' 4CR manifold

A metal-free chemodifferentiating A2BB' 4CR manifold for the modular synthesis of tertiary skipped diynes is described. The manifold performs a triethylamine triggered reaction of alkyl propiolates and acid chlorides to assemble two units of each component in the form of two propargylic alkynoates, a tertiary alcohol, and an ester. A differentiated incorporation of the two acid chloride components ensures functional diversity in the final structure. In addition, the presence of two connected propargylic alkynoates provides a reactive platform for complexity generation.     

Gas chromatographic-mass spectrometric determination of two new antimycotic agents, 1-[(5-chloro-2-benzofuranyl)(2-chlorophenyl)methyl]-1H-imidazole and 1-[(5-bromo-2-benzofuranyl)phenylmethyl]-1H-imidazole, in rabbit plasma following topical administration: a preliminary comparison with bifonazole

A method for the analysis of the antimycotic drugs 1-[(5-chloro-2-benzofuranyl)(2-chlorophenyl)methyl]-1H-imidazole, 1-[(5-bromo-2-benzofuranyl)phenylmethyl]-1H-imidazole and bifonazole in rabbit plasma, employing gas chromatography-mass spectrometry with selected-ion monitoring, was developed. The procedure involved single-step purification of the biological matrix via liquid-liquid extraction on Extrelut columns and use of a carrier substance to minimize the negative effects of adsorption sites during the gas chromatographic process. The limits of detection ranged from 0.1 to 1.4 ng/ml, starting from a 200-microliter sample. The method was applied to a preliminary evaluation of percutaneous absorption of both drugs in the rabbit after a single administration, in comparison with bifonazole.