Synthesis of benzooxepane-fused cyclobutene derivatives via Pd-catalyzed cascade reactions of haloarenes and diynylic ethers.

A tandem palladium-catalyzed Sonogashira coupling, propargyl-allenyl isomerization, and [2+2] cycloaddition sequence between electron-deficient haloarenes and 1,8-diynylic ethers is developed. The reaction shows good functional tolerance and proceeds under mild conditions to provide a new profile of benzooxepane-fused cyclobutene derivatives in moderate to high yields with high selectivity. The reaction mechanism is validated both by experimental studies and DFT calculations.

Synthesis of 1,1,4,5-Tetrasubstituted Phthalans via Pd-Catalyzed Three-Component Reactions of Haloarenes, Alkynes, and Protic Nucleophiles.

A novel approach for the synthesis of 1,1,4,5-tetrasubstituted phthalans is developed via a tandem palladium-catalyzed Sonogashira coupling/propargyl-allenyl isomerization/pentadehydro-Diels-Alder cyclization/regioselective nucleophilic addition sequence. The reaction shows good functional tolerance and provides a wide variety of substituted phthalans in moderate to high yields from haloarenes, triynes, and protic nucleophiles, such as amines and alcohols, under very mild conditions.

Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

Asymmetric Total Syntheses of Aspidodasycarpine, Lonicerine, and the Proposed Structure of Lanciferine.

Aspidodasycarpine and lonicerine are a pair of epimeric aspidophylline-type alkaloids bearing vicinal quaternary C7 and C16. The first and enantioselective total syntheses of these molecules are described here. A Ru-catalyzed asymmetric transfer hydrogenation established the first stereocenter. An Au-promoted Toste cyclization was exploited to assemble the bridged tetracyclic core and define the geometry of the exocyclic olefin; electron deficient (p-CF3C6H4)3P was a suitable ligand for this transformation. An aldol condensation followed by an intramolecular indole C3 alkylation constructed the adjacent quaternary C7 and C16 diastereoselectively, leading to a pentacyclic lactol as an advanced common intermediate for synthesizing both alkaloids. The proposed structure of lanciferine, a highly oxidized congener of aspidodasycarpine, was synthesized from the lactol by tuning the oxidation states of various carbons.

Total Synthesis of Trioxacarcins DC-45-A1, A, D, C, and C7″-epi-C and Full Structural Assignment of Trioxacarcin C.

Trioxacarcins DC-45-A2, DC-45-A1, A, D, C7″-epi-C, and C have been synthesized through stereoselective strategies involving BF3·Et2O-catalyzed ketone-epoxide opening and gold-catalyzed glycosylation reactions, and the full structural assignment of trioxacacin C was deciphered via the syntheses of both of its C7″ epimers. The gathered knowledge sets the foundation for the design, synthesis, and biological evalution of analogues of these natural products as potential payloads for antibody-drug conjugates and other delivery systems for targeted and personalized cancer chemotherapy.

Gold-catalyzed cyclization of 3-(2'-azidoaryl)-1-arylpropargyl carbonates or 3-aryl-1-(2'-azidoaryl)propargyl carbonates to produce quinolines.

A gold-catalyzed cyclization of 3-(2'-azidoaryl)-1-arylpropargyl carbonates to generate substituted quinolines via a sequence of 3,3-rearrangement, 6-endo-trig cyclization and denitrogenation has been developed. Similar products could be obtained from 3-aryl-1-(2'-azidoaryl)propargyl carbonates under different gold catalytic conditions via a sequential 6-endo-dig cyclization, denitrogenation, and 1,2-H shift process.

Synthesis of polycyclic isoindoline derivatives via tandem Pd-catalyzed coupling, propargyl-allenyl isomerization, [4 + 2] cycloaddition and aromatization reaction.

We report in this paper an interesting sequential reaction involving sequential Sonogashira coupling, propargyl-allenyl isomerization, [4 + 2] cycloaddition and aromatization reaction, which provides a facile method for the synthesis of a variety of polycyclic isoindoline derivatives from easily accessible starting materials.

Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles.

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.

Palladium(0)-catalyzed cyclization of 1,6-diyn-3-yl carbonates with a nucleophilic functionality: efficient synthesis of polycyclic benzo[b]fluorene derivatives via allene intermediates.

We report in this paper an interesting tandem reaction involving sequential palladium(0)-catalyzed decarboxylation of diynylic carbonates, intramolecular nucleophilic cyclization and Schmittel reaction, which provides a facile method for the synthesis of a variety of polycyclic benzo[b]fluorene derivatives from easily accessible starting materials.

Unexpected Pd-catalyzed coupling, propargyl-allenyl isomerization and alder-ene reaction: facile synthesis of some not readily available 2,3-dihydrofuran derivatives.

An interesting sequential reaction involving Pd-catalyzed coupling, propargyl-allenyl isomerization, and Alder-ene cycloaddition is reported, providing a facile synthesis of some not readily available 2,3-dihydrofurans from electron-deficient vinyl or aromatic halides and 1-aryl-prop-2-ynyl 3'-methylbut-2'-enyl ethers.

Specific recognition of loop DNA by dicationic porphyrins.

A series of dicationic porphyrins were found to specifically recognize loop structures of oligodeoxynucleotides, and to selectively oxidize guanine residues upon photo-irradiation at micromolar concentrations. These compounds could, thus, be employed as promising structural probes for specific secondary DNA structures. The production of singlet oxygen ((1)O2) is responsible for the DNA-modification profiles. Both UV-titration and thermal-melting experiments indicate that the strong affinity of the charged porphyrins towards DNA loops is responsible for these molecular-recognition phenomena.