A facile one-pot synthesis of 2-substituted-3-aminoquinolines: preparation of benzo[b]naphthyridine-3-carbonitriles

A facile one-pot synthesis of 3-aminoquinolines from ortho-aminobenzaldehydes was developed. Ethyl 6,7-dimethoxy-3-aminoquinoline-2-carboxylate, a key intermediate for the preparation of a 4-anilino-benzo[b][1,5]-naphthyridine-3-carbonitrile, was efficiently prepared by this method. Synthetic routes to 4-anilino-benzo[b][1,5]-naphthyridine-3-carbonitrile and 4-anilino-benzo[b][1,8]-naphthyridine-3-carbonitrile are described     

The Mitsunobu reaction in preparing 3-deazapurine carbocyclic nucleosides

The coupling reaction of 4-chloro-1H-imidazo[4,5-c]pyridine (6-chloro-3-deazapurine, 3) with several cyclopentyl derivatives under Mitsunubo reaction conditions provides an efficient entry into N-7 and N-9 substituted 3-deazapurine carbocyclic nucleosides of antiviral potential. The versatility of this procedure is illustrated with a new and efficient synthesis of (−)-3-deazaaristeromycin, a formal preparation of 3-deazaneplanocin A, and a route to 3-deaza-5′-homoaristeromycin.     

Syntheses of tetrahydropyridin-3-ol and tetrahydroazepin-3-ol from a chiral aziridine-2-carboxylate

A method for the stereoselective preparation of 1,2,3,6-tetrahydropyridin-3-ols and 2,3,4,7-tetrahydro-1H-azepin-3-ols, potentially versatile intermediates in the asymmetric synthesis of various piperidine alkaloids and azasugars, has been developed. The routes start with a readily available optically pure aziridine-2-carboxylate. The design strategy relies on four key transformations involving (1) stereoselective reduction of an acyl-aziridine intermediate derived from the aziridine-2-carboxylate, (2) regioselective aziridine ring opening, (3) N-allylation, and (4) ring-closing metathesis. The method developed in this investigation provides ready access to stereochemically defined and highly functionalized 3-hydroxy-substituted tetrahydropyridines and tetrahydroazepines.     

Engineering of pha operon on Cupriavidus necator chromosome for efficient biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from vegetable oil

Cupriavidus necator H16C_Ac, previously constructed for production of poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) [P(3HB-co-3HHx)] from soybean oil, was further engineered aiming to increase 3HHx composition in the copolyester. PHA synthase gene derived from Aeromonas caviae on the H16C_Ac chromosome was replaced by a gene encoding the N149S/D171G mutant and this recombination enhanced PHA productivity as well as slightly increased 3HHx composition. Manipulation of phaA_Cn locus partially reduced the amount of 3HB unit concomitantly with relative increase of 3HHx composition, whereas deletion of phaB1_Cn resulted in drastic decline of 3HB unit in P(3HB-co-3HHx). Insertion of phaJ_Ac encoding (R)-specific enoyl-CoA hydratase from A. caviae into pha operon significantly enlarged 3HHx fraction without negative effects on the cell growth and polyester accumulation. Consequently, efficient production of P(3HB-co-3HHx) with 3HHx composition of 5.7-9.9 mol% was successfully achieved from soybean oil by the engineered strains.     

Corrosion Behavior of Steel A3 Influenced by Thiobacillus Ferrooxidans

The electrochemical measurement and surface analysis methods were employed to investigate the corrosion behavior of steel A3 influenced by Thiobacillus ferrooxidans (T.f). Polarization curve results indicated that the presence of Thiobacillus ferrooxidans resulted in higher corrosion potential of the electrode and obviously accelerated the corrosion current density. Atomic force microscope (AFM) results showed that asymmetric biofilms adhered to the surface of steel A3 after 7 days of exposure. The scanning electron microscopy (SEM) results showed that pitting appeared on the surface of steel A3 after 7 days of exposure in T.f solution, which was induced by the metabolism of bacteria and the morphology of the deposit. Pitting holes of steel A3 in T.f solution were deeper after 20 days of exposure. The presence of Thiobacillus ferrooxidans aggravated the localized corrosion of A3 steel.     

Synthesis of 3-arylcoumarins via Suzuki-cross-coupling reactions of 3-chlorocoumarin

A convenient, new, and effective protocol for a rapid synthesis of different substituted 3-arylcoumarins is reported. The developed synthetic route involves Pd-catalyzed cross-coupling reaction, using a catalytic complex Pd-salen. Under these conditions, a series of different substituted boronic acids have been successfully reacted with a coumarin halide to afford the coupling products in good yields.     

Phosphine-catalyzed [3+3] annulation reaction of modified tert-butyl allylic carbonates and substituted alkylidenemalononitriles

A phosphine-catalyzed [3+3] annulation reaction of modified tert-butyl allylic carbonates with various alkylidenemalononitriles to form cyclohexenes was developed. The use of protic solvent is crucial in this reaction. When non-polar solvent, toluene or xylene, was used, only non-cyclized product was obtained.     

Efficient and selective deprotection method for N-protected 2(3H)-benzoxazolones and 2(3H)-benzothiazolones

Cyclic carbamate flanked with heterocyclic or aliphatic moieties are frequently used in medicinal chemistry. The synthesis of derivatives bearing a free NH often requires the use of a protection method. A literature search reveals very few protection/deprotection methods for cyclic carbamates. In this paper, we described different methods applicable to 2(3H)-benzoxazolone and 2(3H)-benzothiazolone.     

Solution-phase parallel synthesis of new 2H-pyrimido-[4,5-e][1,2,4]triazin-3-ylidenecyanamides

A practical synthesis of 2H-pyrimido[4,5-e][1,2,4]triazin-3-ylidenecyanamides has been developed. The key step is the coupling reaction of an aryldiazonium salt with 1-cyano-3-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylamino)-2-methylisothiourea followed by intramolecular cyclization. A library of 2H-pyrimido[4,5-e][1,2,4]triazin-3-ylidenecyanamides was prepared in two steps from 6-aminouracils using this method.     

Practical synthesis of (2S,3R)-3-hydroxy-3-methylproline, a constituent of papuamides, using a diastereoselective tandem Michael-aldol reaction

(2S,3R)-3-Hydroxy-3-methylproline, a constituent of cyclodepsipeptides polyoxypeptins A and B, was efficiently synthesized by lithium chloride-induced diastereoselective tandem Michael-aldol reaction using methyl vinyl ketone and N-1-naphthylsulfonylglycine (R)-binaphthyl ester and subsequent hydrolysis of the product in 39% overall yield and five steps.     

Chemoselective synthesis of 3H-pyrrolo[2,3-c]quinolin-4(5H)-one derivatives from 3-phenacylideneoxindoles and substituted tosylmethyl isocyanide (TosMIC)

A simple and convenient synthetic approach to access of 3H-pyrrolo[2,3-c]quinolin-4(5H)-one derivatives by the reaction of (Z)-3-(2-oxo-2-ethylidene)indolin-2-one derivatives 1 with functionalized TosMICs under basic conditions has been reported. The desired products were obtained in good to excellent yields (82–94%). The easy accessibility of the starting materials, simple and mild reaction conditions, short reaction time, and good to excellent chemical yields make this methodology highly efficient.     

Preparation of 2,2-disubstituted 1,2-dihydro-3H-indol-3-ones via oxidation of 2-substituted indoles and Mannich-type reaction

A novel preparative method for 2,2-disubstituted 1,2-dihydro-3H-indol-3-ones through the oxidation of 2-arylindoles followed by a Mannich-type reaction with carbon nucleophiles is described.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

A facile synthesis of naturally occurring 5-(3-indolyl)oxazoles

A simple and efficient synthesis of naturally occurring 5-(3-indolyl)oxazoles is described. The key steps of this convergent approach are the formation of a 3-tosyloxyacetyl-1-benzenesulfonylindole, a 3-amino-acetyl-1-benzenesulfonylindole hydrochloride and cyclodehydration of an α-acylaminoketone.     

Synthesis of 3-substituted 3H-indol-3-ols by the reaction of 2-isocyanophenyl ketones with Grignard reagents

A facile method for the synthesis of 3-substituted 3H-indol-3-ols has been developed. Thus, 2-isocyanophenyl ketones are allowed to react with various Grignard reagents to give the corresponding desired indolol derivatives in generally fair to good yields. The formation of 3-aryl-2,3-dimethylindolin-3-ols by the reaction of 2-isocyanobenzophenones with 2 M amounts of methylmagnesium bromide is also reported.     

Saikachinoside A, a novel 3-prenylated isoguanine glucoside from seeds of Gleditsia japonica

A new isoguanine glucoside designated saikachinoside A has been isolated from the seeds of Gleditsia japonica. The structure was determined as 7-β-d-glucopyranosyl-3-[(Z)-4-hydroxy-3-methyl-2-butenyl]isoguanine by interpretation of the spectroscopic data and was confirmed by X-ray crystallographic analysis. Saikachinoside A accelerated acetylcholinesterase activity.     

Carbon dioxide-mediated synthesis of 3(2H)-furanones from diyne alcohols

A novel type of carbon dioxide-mediated reaction of diyne alcohols without any metal catalysts was reported. Carbon dioxide held the key to the success of this reaction, in which 3(2H)-furanones were selectively obtained in moderate to high yields.     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

3-Halomethylated cyclic nitronates: synthesis and nucleophilic substitution

A method for the introduction of a halogen atom into the methyl group attached to the C-3 atom of five- and six-membered cyclic nitronates (isoxazoline N-oxides and oxazine N-oxides, respectively) has been studied. The process involves silylation of starting 3-methyl-substituted cyclic nitronates followed by halogenation of the resulting N-(silyloxy)enamines. While five- and six-membered cyclic enamines behave similarly toward elemental bromine and iodine, their reactions with NBS give different products, that were rationalized by stereoelectronic effects. The obtained halogenated nitronates were coupled with various nucleophiles affording new nitronates functionalized at the C-3 position.     

A mild and efficient method for large scale synthesis of 3-aminocoumarins and its further application for the preparation of 4-bromo-3-aminocoumarins

A wide variety of 3-aminocoumarins have been synthesized in large scale from the corresponding 3-acetamidocoumarins by regioselective cleavage of carbon–nitrogen bond using 70% sulfuric acid under reflux conditions. The synthesized 3-aminocoumarins were further brominated regioselectively at the 4-position of 3-aminocoumarin using BDMS as brominating agent.