Construction Of Skeleton Research Articles

Synthesis of Acyl Cyclopentaquinolinones through Simultaneous Construction of the Heterocyclic Scaffold and Introduction of the Acyl Group.

Presented herein is an effective and concise synthesis of acyl cyclopentaquinolinone derivatives via the cascade reactions of N-(o-ethynylaryl)acrylamides with α-diazo carbonyl compounds. The formation of product involves a visible light-induced radical formation from α-diazo carbonyl compound followed by its addition onto the acrylamide moiety to trigger double radical annulation, single-electron oxidation, and β-elimination. To our knowledge, this is the first example in which the cyclopentaquinolinone scaffold was constructed along with the introduction of an acyl group under visible light irradiation conditions. Compared with literature methods for similar purpose, this newly developed protocol has advantages such as readily accessible substrates, mild reaction conditions, valuable products, concise synthetic procedure, and high sustainability. With all these merits, this method is expected to find wide applications in the construction of related acyl heterocyclic skeletons.

Bioinspired Collective Total Synthesis of (±)-Rhynchines A-E.

Herein, we present the first racemic total synthesis of the structurally complex monoterpene indole alkaloids rhynchines A-E, starting from commercially available methyl nicotinate and 3-(2-bromoethyl)-1H-indole. The success of our synthesis is attributed to the utilization of a bioinspired synthetic strategy, which facilitated the rapid construction of the pentacyclic core skeleton of the target molecules through biomimetic skeletal rearrangement and late-stage C-H oxidative cyclization. Additionally, silica-gel-promoted tautomerization played a crucial role as a strategic element in the chemical synthesis of rhynchines A and B.

Stereodivergent Synthesis of Alkaloid (±)-223A and (±)-6-epi-223A via Rh-Catalyzed Hydroformylation Double Cyclization.

A stereodivergent approach toward total syntheses of Dendrobatid alkaloids 223A and 6-epi-223A is described. The approach features a concise construction of an indolizidine skeleton by Rh-catalyzed domino hydroformylation double cyclization and sequential stereocontrolled transformations such as reductive alkylation or anti-selective α-alkylation of the 5-oxoindolizidine. These stereoselective reactions afford the desired stereochemistry in the targets.

Total synthesis of (±)−paralemnolin A

The first total synthesis of chlorinated tricyclic norsesquiterpenoid paralemnolin A in racemic form was achieved. The synthesis features chlorolactonization of a cyclohexene derivative having a tert-butyl ester, construction of the novel tricyclic skeleton by an intramolecular Reformatsky–Honda reaction, and methylenation of the carbonyl group of the lactone moiety with Tebbe reagent.

Construction of Diverse Pyrrolidine-Based Skeletons through the Ag-Catalyzed Stereoselective Addition-Elimination Reaction of Azomethine Ylides with Nitroallyl Acetates.

Because scaffold diversity has a pronounced impact on biological screening, the efficient and expedient construction of skeletally diverse compound collections is a fundamental demand in drug discovery. In this regard, we report here an asymmetric tandem conjugate addition-elimination reaction of pyrroline esters with nitroallyl acetates and its application to the construction of various types of fused or spirocyclic pyrrolidines. A AgOAc/(R,Sp)-ThioClickFerrophos (TCF) catalyst efficiently promotes the addition-elimination reaction, setting vicinal chiral stereocenters featuring a tetrasubstituted carbon with excellent enantio- and diastereoselectivity while leaving the versatile nitroolefin moiety. The broad substrate scope of this reaction and the transformability of the resulting nitroolefin, imine, and ester moieties allow for the construction of diverse pyrrolidine-based fused or spiro bicyclic skeletons in optically active forms by various intramolecular cyclization processes.

Construction of an Angular Tricyclic Benzofuran Skeleton Using the C-H Activation Strategy.

A protocol for the construction of an angular tricyclic benzofuran skeleton based on the C-H activation strategy has been established. Different phthalide lactones on this skeleton can be easily assembled with various side chains by using C-H activation with aldehydes and subsequent reduction. This skeleton provides a versatile and crucial motif for the total synthesis of naturally occurring angular tricyclic benzofurans and their derivatives. Based on this protocol, the improved total syntheses of daldinin A and annullatin D were achieved in yields of 17.3 and 7.6%, respectively.

Collective total synthesis of stereoisomeric yohimbine alkaloids

Stereoisomeric polycyclic natural products are important for drug discovery-based screening campaigns, due to the close correlation of stereochemistry with diversified bioactivities. Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the ten-carbon building block. In this work, we reset the stage by the development of a bioinspired coupling, in which the rapid construction of the entire pentacyclic skeleton and the complete control of all five stereogenic centers are achieved through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate. The stereochemical diversification from a common intermediate allows for the divergent and collective synthesis of all four stereoisomeric subfamilies of yohimbine alkaloids through orchestrated tackling of thermodynamic and kinetic preference.

Towards non-traditional intrinsic luminescence luminogens from polystyrene derivative C5 skeletal polymers and ladder polymers with well-regulated microstructures

With the emergence of new emissive species in many nonconjugated structures, how to efficiently design and manipulate non-traditional intrinsic luminescence luminogens (NTILgens) is of academic importance but a dramatic challenge. As the carbon skeletons in olefin polymers have diverse microstructures that mainly affect molecular packing, the construction of the carbon skeletons is required to regulate the performances of luminescent materials. Our group previously reported the C5 skeletal P-CPVB and its ladder polymer (C-PCPVB) through the anion migrated ring-opening polymerization (AMROP) of 1-cyclopropylvinylbenzene (CPVB) and the cationic cyclization of P-CPVB. Unexpected, after the rigid seven membered rings were constructed among the phenyl rings, the NTIL was observed of the nonconjugated C-PCPVB in the aggregate state under UV light irradiation. The results inspired us to design the polymer luminogens through the construction of carbon skeletons. In present work, the P-CPVBs and their ladder polymers (C-PCPVBs) with different degree of polymerization (DPs) are prepared. Unexpected, P-CPVBs with different DPs were non-emissive in dilute solution but highly emissive with the visible light in the solid state under the UV light irradiation. As predicted, C-PCPVBs with different DPs fluoresced blue emission in the aggregation state. All the P-CPVBs in the solid state showed much higher absolute quantum yields (QY) values than C-PCPVB analogues did. The bright blue emissions in the aggregate state of both C-PCPVBs bearing nonconjugated groups and P-CPVBs bearing poorly conjugated groups could be attributed to the clusterization-triggered emission (CTE), but the mechanisms to generate NTIL were different due to the difference of the carbon skeletons, where the through-spacing conjugation (TSC) and through-spacing interactions (TSI), respectively, contributed to the NTIL of C-PCPVBs and P-CPVBs. In perspective of the property-oriented designability, their derivatives with different electron-donating and -withdrawing substituents (P-CPVB-OCH3/TPSE/yne, C-PCPVB-OCH3/TPSE/yne) when the DPs were fixed at 24 were synthesized and characterized. All the substituted P-CPVBs/C-PCPVBs were demonstrated with the aggregation-induced emission (AIE) effect and blue fluorescence as the unsubstituted P-CPVBs/C-PCPVBs. As desired, the electronic effect of carbon skeletons and their cyclization can affect their maximum emission wavelengths (λem) and the QY. All the λem values were red-shifted whether the carbon skeletons were cyclic or substituted. More importantly, the glass temperature (Tg) and decomposition temperature (Td) of P-CPVB were dramatically improved by the substituents and cyclization analogues. The seven-membered ring and the crosslinking networks of the yne group in the warming up can significantly improve the stability of polymers, contributing to the higher Td value. It should be noted that P-CPVB-yne and C-PCPVB-yne exhibited the much higher Td values, and they showed the higher carbonization yield of 49.78% and 45.25% at 800 ℃, respectively, which would broaden their applications of these nonpolar polymers.

Unraveling the Synergistic Effects of Oxygen Vacancy and Amorphous Structure on TiO2 for High‐Performance Lithium Storage

The improved electronic conductivity and ion diffusion efficiency of TiO2‐based anode materials have been extensively studied by introducing oxygen vacancies or creating amorphous structure. There has been little exploration of the synergistic effects by combining these two modification strategies into one TiO2‐based matrix. In addition, the structure–activity relationship and energy storage mechanism involved remain to be understood. Herein, a facile one‐step coreduction method is reported to successfully produce the oxygen vacancy‐doped amorphous TiO2 nanoparticles. The oxygen vacancy‐doped amorphous TiO2 anode exhibits significantly enhanced electrochemical activity and high‐rate stability (up to 87 mAh g−1 over 10 000 discharge/charge cycles at a current rate of 100 C). This outstanding electrochemical performance is attributable to the synergistic effects of amorphous structure and oxygen vacancies. Density functional theory calculations reveal the enhanced electronic conductivity and thermodynamically favorable lithium insertion architecture due to the introduction of oxygen vacancy and the construction of the amorphous skeleton. Dynamic analysis indicates that the lithium‐storage mechanism is a hybrid of surface capacitive storage and enhanced diffusion‐controlled ion insertion. This work opens up new pathways in developing novel anode materials for efficient energy storage from the wide spectrum of metal oxides.

Photocatalytic organosulfur reagent-promoted selective mono-(deutero)hydrodechlorination

Selective partial C–Cl bond reduction represents an important strategy for the construction of valuable chlorine-containing skeletons.

Phosphine-catalyzed enantioselective and diastereodivergent [3+2] cyclization for the construction of oxetane dispirooxindole skeletons.

We have developed a phosphine catalyzed asymmetric [3+2] cyclization of 3-oxetanone derived MBH carbonates with activated methyleneoxindole, to construct oxetane dispirooxindole skeletons. Diastereodivergent synthesis was realized via the control of the phosphine catalyst. The (-)-DIOP provides the syn diastereoisomers, while the spiro phosphine (R)-SITCP achieves the anti-epimers.

Recent advances in photochemical strain-release reactions of bicyclo[1.1.0]butanes.

Bicyclo[1.1.0]butanes (BCBs) are attractive compounds for their beautiful "butterfly" conformations, distinctive properties, and novel reactivities. As soon as the first example had been synthesized, a wide range of strain-release reactions were explored for the preparation of cyclobutanes and bicyclic systems in the ground state or excited state. In particular, with the demand for the construction of rigid three-dimensional aliphatic skeletons to "escape from flatland" in drug discovery programs, numerous efforts have been devoted in this area to expanding the boundaries of their reactivities and broadening the chemical space of their attractive bioisosteric products. In recent years, with the great resurgence and dramatic evolution of photochemistry, photochemical strain-release reactions generally relying on single electron transfer (SET) or energy transfer (EnT) strategies can provide much more opportunities and capability for innovative transformations of BCBs. In this review, we summarize and highlight the recent advances (year > 2016) of this topic and hope that it will inspire much more wonderful chemistry of BCBs.

Photochemical three-component assembly of tri-substituted oxazoles through a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade.

Construction of complex molecular skeletons with ubiquitous chemical feedstocks in a single transformation is highly appealing in organic synthesis. We report a novel visible-light-induced three-component reaction for the construction of complex 2,4,5-trisubstituted oxazoles, which are valuable in medicinal chemistry, from simple and readily available iodonium-phosphonium hybrid ylides, carboxylic acids, and nitriles. This reaction features a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade, in which a photo-generated α-phosphonium carbene acts as a sequence trigger. This catalyst- and additive-free transformation exhibits high efficiency and broad substrate scope for synthesizing diverse oxazoles.

Me3SiBr-promoted cascade electrophilic thiocyanation/cyclization of ortho-alkynylanilines to synthesize indole derivatives.

A Lewis acid-promoted electrophilic thiocyanation/cyclization of ortho-alkynylanilines for the synthesis of indole derivatives has been developed. The reaction utilizes Me3SiBr as the Lewis acid and N-thiocyanatosuccinimide as the thiocyanation reagent. A series of 2-aryl-3-thiocyanato indoles were prepared in moderate to high yields under mild conditions without metals and oxidants. It provides an efficient protocol for the construction of the indole skeleton and C-SCN and C-N bonds in one step as well.

Construction of macroporous MOF-derived single leaf-like cellular skeleton for boosting advanced oxidation processes

A single leaf-like cellular NiCoOv skeleton derived from macroporous–microporous ZIF-L crystal is synthesized, with enhanced mass transfer and rich active sites for boosting the catalytic activity towards advanced oxidation processes.

Regioselective synthesis of N-containing polycyclic compounds via radical annulation cyclization of 1,7-dienes with aldehydes.

A convenient method for oxidant-promoted radical cascade acylation or decarbonylative alkylation of 1,7-dienes with aldehydes has been established. This method allows for the rapid construction of N-containing polycyclic skeletons in a highly regio- and stereoselective manner. This transformation provides a simple and efficient method for the preparation of a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives by sequential formation of three new carbon-carbon bonds. Additionally, this radical cascade cyclization can selectively convert aldehydes into aroyl/primary aliphatic acyl radicals and secondary or tertiary alkyl radicals.

Total synthesis of 1,4a-di-epi-ent-pancratistatin, exemplifying a stereodivergent approach to pancratistatin isomers.

The total synthesis of 1,4a-di-epi-ent-pancratistatin, a novel stereoisomer of the anti-tumor Amaryllidaceae alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The construction of the pancratistatin skeleton involved conjugate addition of organocuprate to a nitrosoolefin, which was generated in situ from inosose oxime. This was followed by stereoselective reduction of the oxime to an amine and site-selective formylation. Biological evaluations revealed that the newly synthesized compounds exhibit cytotoxicity toward cancer cells and significant ferroptosis inhibitory activity. These compounds constitute a promising small-molecule library for the development of potent bioactive agents.

Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N‐N Axis†

Comprehensive SummaryAtroposelective synthesis of N‐N atropisomers is an emerging area but remains underexplored; in particular, the synthesis of N‐N benzimidazole atropisomers is still unprecedented. Herein, the first enantioselective synthesis of N‐N benzimidazole atropisomers via the palladium‐catalyzed de novo construction of benzimidazole skeleton is presented. With readily available palladium catalyst and biphosphine ligand, a broad range of nonbiaryl benzimidazole and indole‐benzimidazole atropisomers were conveniently accessed in high yields and with excellent enantioselectivities. Significantly, these N‐N benzimidazole atropisomers showed great antitumor activity and selectivity to breast cancer MCF‐7 cells. The simple catalytic system, broad substrate scope, high enantioselectivity, and good bioactivity make this approach highly attractive.

Iodine-Mediated Heterocyclization for the Synthesis of 6-Alkylthio-1,3,5-triazine-2,4-diamines from N-Alkylpyridinium Salts and NH4SCN.

An iodine-mediated method for the synthesis of 6-alkylthio-1,3,5-triazine-2,4-diamines by the reaction of N-alkylpyridinium salts and NH4SCN in air is reported. Twenty-seven compounds were obtained under the standard conditions. Pyridinium salts work as benzyl-group transfer reagents to promote the formation of the CBn-SSCN bond and thereby the construction of the triazine skeleton. A plausible mechanism is proposed based on the experimental results and literature survey.

Construction of Polyheterocyclic Skeletons through C−H Bond Activation‐Initiated Cascade Reactions by Using Cyclopropanol as Alkylating Agent as well as Masked Nucleophile and Electrophile

AbstractPresented herein is a synthesis of indane fused bicyclic pyrazolidinones based on the reactions of aryl azomethine imines with cyclopropanols. Mechanistically, the formation of product involves Rh(III)‐catalyzed direct aryl C(sp2)−H alkylation of aryl azomethine imine with cyclopropanol through in situ ring‐opening, followed by cascade intramolecular C‐ and N‐nucleophilic addition. In this tandem process, cyclopropanol acts as not only an alkylating agent but also masked nucleophile and electrophile to participate in the construction of both the indane and the bicyclic pyrazolidinone scaffolds. To our knowledge, such a cascade reaction pattern has not been disclosed. In general, this synthetic protocol has advantages such as easily obtainable substrates, valuable products, concise synthetic procedure, unique reaction pathway, and good compatibility with diverse functional groups.