Functionalisation of the uracil ring via palladium-catalysed aminocarbonylation

Iodouracil derivatives (5-iodouracil, 5-iodo-1,3-dimethyluracil) were aminocarbonylated using a set of primary and secondary amines in the presence of in situ palladium(0) catalysts. The formation of carboxamides via single CO insertion was favoured at atmospheric CO pressure. The chemoselectivity toward double CO insertion can be increased by using 40 bar of CO pressure, in this way up to 60% selectivity toward 2-ketocarboxamide was achieved. In the case of 5-iodouracil the corresponding 5-glyoxylamido-uracil derivatives were exclusively formed at 40 bar CO pressure. The only exception is the less basic aniline nucleophile which provided the corresponding carboxamide exclusively. A typical side-reaction took place when 5-iodouracil was used as substrate: this heterocycle, existing in lactam-lactim tautomeric forms, underwent deiodination providing the parent uracil as side-product.     

Synthesis of novel 1,2,3-triazolyl nucleoside analogues bearing uracil, 6-methyluracil, 3,6-dimethyluracil,thymine, and quinazoline-2,4-dione moieties

A series of novel 1,2,3-triazolyl nucleoside analogues was synthesized via the CuAAC reaction of N1-alkynyl uracil, 6-methyluracil, 3,6-dimethyl uracil, thymine and quinazolin-2,4-dione with protected azido β-d-ribofuranose. The obtained compounds differ in both the nature of the pyrimidine-2,4-dione fragment and the length of the polymethylene linker connecting it with the β-d-ribofuranosyl-1,2,3-triazol-4-yl moiety. The 1,2,3-triazolyl nucleoside analogues were evaluated for their cytotoxicity in vitro.     

Pd(II)-catalyzed regioselective direct arylation of uracil via oxidative Heck reaction using arylboronic acids

A palladium catalyzed regioselective synthesis of 6-aryl uracils via oxidative Heck reaction (C–H bond functionalization) of uracils and arylboronic acids is reported. The method is simple, atom-economical, and high yielding.     

A convergent approach towards the synthesis of the 2-alkyl-substituted tetrahydroquinoline alkaloid (−)-cuspareine

A convergent approach towards the synthesis of the 2-alkyl-substituted tetrahydroquinoline alkaloid (?)-cuspareine via enantiospecific construction of the (R)-benzyl 2-formyl-3,4-dihydroquinoline-1(2H)-carboxylate. We have achieved an efficient enantiospecific synthesis of (?)-cuspareine starting from known key starting materials. The reactions employed for individual transformations are simple and high yielding, and the strategy could potentially be easily extended.     

An efficient synthesis of an 8-phenoxy aporphine derivative utilizing mono-ligated palladium ortho-phenol arylation

8-Aryloxy aporphines are a structurally diverse subset of alkaloids that display an array of biological activities. An efficient synthesis of an 8-phenoxy aporphine model compound has been developed utilizing Pictet-Spengler cyclization followed by biaryl bond formation using Pd-XPhos catalyzed ortho-phenol arylation. Biaryl bond formation using direct arylation is also compared. Finally, the stability of the 8-phenoxy aporphine model compound is discussed with potential implications for the isolation, structure elucidation and pharmacognosy of 7-dehydroaporphine natural products.     

Site-selective direct arylation of unprotected adenine nucleosides mediated by palladium and copper: insights into the reaction mechanism

Reaction conditions facilitating the site-selective direct aryl functionalisation at the C-8 position of adenine nucleosides have been identified. Many different aromatic components may be effectively cross-coupled to provide a diverse array of arylated adenine nucleoside products without the need for ribose or adenine protecting groups. The optimal palladium catalyst loading lies between 0.5 and 5 mol %. Addition of excess mercury to the reaction had a negligible affect on catalysis, suggesting the involvement of a homogeneous catalytic species. A study by transmission electron microscopy (TEM) shows that metal containing nanoparticles, ca. 3 nm with good uniformity, are formed during the latter stages of the reaction. Stabilised PVP palladium colloids (PVP=N-polyvinylpyrrolidone) are catalytically active in the direct arylation process, releasing homogenous palladium into solution. The effect of various substituted 2-pyridine ligand additives has been investigated. A mechanism for the site-selective arylation of adenosine is proposed.     

Metal- and acid-free,TBN-mediated direct CH nitration of arenes

A metal-free, acid-free, direct and eco-friendly nitration methodology has been developed. A tert-butyl nitrite efficiently promotes the direct CH nitration of electron-rich arenes with good to excellent yields and regioselectivities. The practical utility of this protocol has been demonstrated in gram-scale nitration of crown ether and mono nitration of Sesamin. A plausible free radical mechanism is proposed based on detailed experimental observations.     

A one-pot and three-component synthetic approach for the preparation of asymmetric and multi-substituted 1,4-dihydropyrazines

An efficient, one-pot and three-component synthesis of a new series of 2-acyl-3,4,6-triaryl-1,4-dihydropyrazines is described. This two-step strategy involves treatment of phenacyl bromides and anilines to give the nucleophilic substitution intermediate followed by Michael-addition-cyclization to α-azidochalcones to afford the title compounds in high yields.     

Synthesis of chiral quaternary fluorinated cyclic sulfamidates via palladium-catalyzed arylation with arylboronic acids

An enantioselective palladium-catalyzed arylation of fluorinated cyclic N-sulfonyl ketimines with arylboronic acids is described. This methodology provides an efficient and convenient route to chiral quaternary fluorinated cyclic sulfamidates in high yields with up to 99% ee.     

Copper(II)-catalyzed preparation of alkylindium compounds and applications in cross-coupling reactions both in aqueous media

An efficient water-based method for the synthesis of alkylindium compound in the presence of a catalytic amount of cheap and readily available CuSO₄·5H₂O (10 mol%) was developed. The thus-generated alkylindium compounds effectively underwent palladium-catalyzed cross-coupling reactions with a myriad of aryl halides in aqueous media, leading to the cross-coupled products in modest to high yields. The mildness of the formed alkyl organometallics allowed the tolerance to various important functional groups incorporated in both substrates of alkyl iodides and aryl halides.     

Pd-catalyzed Suzuki/Sonogashira cross-coupling reaction and the direct sp3 arylation of 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine

A rapid and efficient method is reported for the synthesis of the [1,2,4]triazolo[1,5-a]pyrimidine motif. Palladium catalyzed Suzuki and Sonogashira cross coupling reactions on 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine were performed. The direct sp³ arylation of compounds resulting from the Suzuki reaction was then carried out.     

An efficient approach to isoquinoline via AgNO3-promoted 6-endo-dig cyclization followed by oxidative elimination of o-alkynylarylaldimines and its application in fluoride recognition

A novel 6-endo-dig cyclization followed by oxidation/elimination of o-alkynylarylaldimines with 4-hydroxybenzylamine was developed for preparation of isoquinolines. The intermediates of this tandem reaction were monitored by mass spectroscopy (MS) to confirm the reaction pathway. This methodology was further applied to the design and synthesis of a novel ratiometric chemosensor for determination of fluoride.     

Pd/Cu bimetallic co-catalyzed direct 2-arylation of benzoxazole with aryl chloride

An efficient Palladium/Copper bimetallic co-catalyzed direct 2-arylation of benzoxazoles with aryl chlorides is presented. The Pd(OAc)₂/CuI/NiXantphos-based catalyst enables the installation of various aryl and heteroaryl groups in good to excellent yields (75–99%). Preliminary mechanism investigation indicates that Pd/Nixantphos complex activates C-Cl bond of aryl chlorides via oxidative addition, and Cu/Nixantphos complex chelates with nitrogen atom to lower the pK_a of the 2-H in benzoxazoles.     

Euphatexols A and B,two unusual euphane triterpenoids from the latex of Euphorbia resinifera

Two unusual euphane triterpenoids, named euphatexols A (1) and B (2), were isolated from the latex of Euphorbia resinifera. Their structures were elucidated based on the extensive analysis of spectroscopic data (HRMS, 1D and 2D NMR). Compound 1 possesses a rare tetrahydrofuran ring formed via C-1 and C-11, which is firstly reported in euphane triterpenoids. Compound 2 represents an unusual 27-nor-euphane triterpenoid. Moreover, compounds 1 and 2 showed significant cytotoxic activities against HepG2 cells with 87.0% and 87.4% inhibition rate at 1 μM, respectively.     

A novel approach to produce monodisperse hollow pure silica spheres

In this work, we report an efficient method to produce pure hollow silica spheres (HSS) using phenyltrimethoxysilane (PTMS) compound. The production of HSS was carried out via hydrolysis of PTMS in the aqueous media and followed by a condensation reaction to form silica spheres with phenyl groups. The product was then calcined to remove phenyl groups and obtain pure silica spheres with >95% fine structure. The chemical nature of pure silica was confirmed by Fourier transforms infrared spectroscopy. The calcined HSS were stable beyond the temperature of 900 °C as confirmed by thermal gravimetric analysis (TGA). The calcined spheres preserved their spherical appearance and hollow core as shown by SEM and TEM micrographs. Interestingly, the average size of the spheres was reduced significantly after calcination from 760 to 510 nm, confirming further the removal of phenyl groups. The calcined HSS offered much higher surface area (A_s) when analysed by BET; A_s for calcined product was ～406 and mere ～4.8 m²/g for uncalcined HSS. Finally, drug release study of cisplatin/HSS showed over 45% of steady cumulative release for 72 h. The prepared HSS can be dispersed in water opening the possibility of many novel bio/non-bio applications.     

A convenient method for N-1 arylation of uracil derivatives

1-(4-Nitrophenyl)- and 1-(2,4-dinitrophenyl)uracil derivatives have been obtained by direct arylation of uracil and its 5-substituted derivatives using 1-fluoro-4-nitrobenzene or 1-fluoro-2,4-dinitrobenzene in the presence of a base. The application of the newly obtained uracil derivatives in further synthesis is also presented.     

Analogues of the 2-carboxyl-6-hydroxyoctahydroindole (CHOI) unit from diverging Pd-catalyzed allylations: Selectivity as a function of the double bond position

Pd-catalyzed allylations of cyclic bis-allylic substrates, carried out either as two separate steps or in a pseudo-domino fashion, can generate 2-carboxyl-hexahydroindoles bearing an unsaturation in different positions. Sequential homologation, and epoxidation or syn-dihydroxylation steps were investigated to access analogues of the bicyclic 2-carboxyl-6-hydroxyoctahydroindole motif of aeruginosins, a family of peptides displaying serine protease inhibitor activity.     

Iron/copper co-catalyzed highly selective arylation of sulfinamides with aryl iodides

In the present study, an inexpensive but efficient Iron(III) and Copper(II) co-catalyst without ligands catalyzed arylation of sulfinamides with aryl iodide was primarily reported. In brief, in the presence of Fe(NO₃)₃·9H₂O, CuO and K₃PO₄, the highly selective C–N cross coupling of several sulfinamides and aryl iodides was achieved in high chemical yield, while the aryl chlorides and bromides could not yield coupling products. It is noteworthy that through the arylation of chiral tert-butanesulfinamide with aryl iodides, N-aryl tert-butanesulfinamides are provided without racemization, even in gram-scale. The possible mechanism was that This oxidative addition process between copper catalyst and aryl-iodides might be significantly accelerated by active Fe(III) species. Moreover, using this synthetic method, a facile and efficient access was developed for the derivatives of N-phenyl sulfinamides, which might help to develop new drug molecules and material chemicals.     

Platinum electrode modified with polyterthiophene doped with metallic nanoparticles,as sensitive sensor for the electroanalysis of ascorbic acid (AA)

A novel electrochemical sensor for ascorbic acid (AA) detection based on platinum electrode modified with polyterthiophene (P3T) and doped with metallic particles (Cu, Co, Ag, Au, Pd) was constructed. The electrocatalytic performances of the modified electrode with polyterthiophene-metallic particles related to the detection of AA, showed a better catalytic activity compared to the modified electrode with polyterthiophene film. The obtained results demonstrate also that the use of P3T–Ag nanocomposite allows a good sensitivity; which gives a high response in oxidation peak of AA. In order to have a good performance using this sensor, several parameters such as polymerization time of the film and immersion time of the film in AgNO₃ solution were optimized.     

Hyphenone A,the first 3,3-diisoprenylated bicyclic polyprenylated acylphloroglucinols as Cav3.1 T-type calcium channel inhibitor from Hypericum henryi

Hyphenone A (1), a new type of bicyclic polyprenylated acylphloroglucinols (BPAPs) featured with an unprecedented 3,3-diisoprenylated 1,3,5-trione core, were characterized from the roots of Hypericum henryi together with two new congeners (hyphenones B–C, 2–3) and five known biosynthetic related PPAPs. Biogenetically, 1 should be derived from a novel 3,3,5,5-tetraisoprenylated MPAPs precursor. Their structures were elucidated by comprehensive spectroscopic data and X-ray diffraction. Moreover, 1–3 were identified as the first PPAPs type Ca_v3.1 T-type calcium channel (TTCC) inhibitors, with IC₅₀ values of 7.07, 6.19, and 5.47 μM, respectively.