Revisited Mechanistic Implications of the Joullié–Ugi Three-Component Reaction

The effect of the solvent on the diastereoselectivity of the Joullié–Ugi three-component reaction (JU-3CR) using an α-substituted five-membered cyclic imine is revisited. The <i>cis</i> and <i>trans</i> isomers were generated in toluene and HFIP, respectively. Hammett analysis of the JU-3CR suggests the presence of two reaction mechanisms

Total Synthesis of Quinaldopeptin and Its Analogues

The first total synthesis of quinaldopeptin (<b>1</b>) was accomplished. Our approach to the synthesis of <b>1</b> includes the solid-phase peptide synthesis of the linear decapeptide <b>4</b> followed by macrocyclization and introduction of the quinoline chromophores <b>2</b> at a late stage of the synthesis. As for the preparation of <b>4</b>, a fragment coupling approach was applied considering the <i>C</i>2 symmetrical structure of <b>1</b>. Chromophore analogues <b>22</b> and <b>23</b> and desmethyl analogue <b>27</b> were also prepared in a manner similar to the synthesis of <b>1</b>. Synthetic <b>1</b> exhibits a strong cytotoxicity with the IC₅₀ value of 3.2 nM. On the other hand, the activity of <b>23</b> and <b>27</b> was largely reduced

Development of the Carboxamide Protecting Group, 4-(<i>tert</i>-Butyldimethylsiloxy)-2-methoxybenzyl

The new carboxamide protecting group, 4-(<i>tert</i>-butyldimethylsiloxy)-2-methoxybenzyl (SiMB), has been developed. While this SiMB group can be removed using mild basic desilylation methods, it can also be deprotected under strongly acidic or oxidative conditions. An application of this group to simple carboxamide groups, as well as to more complex and acid-sensitive adenosine derivatives containing a cyclophane scaffold, was also demonstrated

Total Synthesis of Plusbacin A₃ and Its Dideoxy Derivative Using a Solvent-Dependent Diastereodivergent Joullié–Ugi Three-Component Reaction

Full details of our synthetic studies toward plusbacin A₃ (<b>1</b>), which is a depsipeptide with antibacterial activity, and its dideoxy derivative are described. To establish an efficient synthetic route of <b>1</b>, a solvent-dependent diastereodivergent Joullié–Ugi three-component reaction (JU-3CR) was used to construct <i>trans</i>-Pro­(3-OH) in a small number of steps. Two strategies were investigated toward the total synthesis. In the first synthetic strategy, the key steps were the <i>trans-</i>selective JU-3CR and a macrolactonization at the final stage of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3-hexa­fluoro­isopropanol provided the <i>trans</i> products, and the coupling of the fragments to prepare the macrocyclization precursor proceeded smoothly. However, attempts toward the macrolactonization did not provide the desired product. Then, the second strategy that included esterification in an initial stage was investigated. Methods for constructing <i>trans</i>-Pro­(3-OH) were examined using a convertible isocyanide, which could be converted to a carboxylic acid required for the following amidation. Ester bond formation was achieved through an intermolecular coupling using a hydroxyl-Asp derivative and the corresponding alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization of the linear peptide gave the cyclic depsipeptide, and then the global deprotection accomplished the total synthesis of <b>1</b> and its dideoxy derivative

Synthesis of <i>C</i>‑Glycosyl Pyrrolo[3,4‑<i>c</i>]carbazole-1,3(2<i>H</i>,6<i>H</i>)‑diones as a Scaffold for Check Point Kinase 1 Inhibitors

Indolocarbazole natural products are known to possess a variety of biological activities that hold promise as cancer chemotherapeutic agents. We newly designed <i>C</i>-glycosyl pyrrolo­[3,4-<i>c</i>]­carbazole-1,3­(2<i>H</i>,6<i>H</i>)-dione derivatives <b>7</b> and <b>8</b>, which are natural-product-like scaffolds. Compounds <b>7</b> and <b>8</b> were stereoselectively and efficiently synthesized using β-selective <i>C</i>-allylation, Heck reaction, and thermal 6π-electron cyclization/oxidative aromatization. Their potential as Chk1 inhibitors was investigated, and <b>7</b> and <b>8</b> exhibited an inhibitory activity with IC₅₀ values of 0.5–9.5 μM, which is good activity for scaffolds. The key intermediate <b>23</b> was obtained by five steps from d-ribose in 33% overall yield by this synthetic route, which would enable us to prepare a range of analogues in order to investigate further structure–activity relationship studies in the optimization process

Total Synthesis of Tunicamycin V

The total synthesis of tunicamycin V is described. This strategy is based on the initial construction of tunicaminyluracil, which is regarded to play an important role in the observed biological activities. The key to the synthesis was a Mukaiyama aldol reaction followed by a furan-oxidation to construct the undecose skeleton, a [3,3] sigmatropic rearrangement of a cyanate, and a highly selective trehalose-type glycosylation

Tris(azidoethyl)amine Hydrochloride; a Versatile Reagent for Synthesis of Functionalized Dumbbell Oligodeoxynucleotides

Triazole-cross-linked oligodeoxynucleotides were synthesized using the Cu(I) catalyzed alkyne–azide cycloaddition with tris(azidoethyl)amine hydrochloride and oligodeoxynucleotides possessing <i>N</i>-3-(propargyl)thymidine at both the 3′- and 5′-termini. Further installation of a functional molecule to the dumbbell oligodeoxynucleotides was achieved by utilizing the remaining azide group

Total Synthesis of Sandramycin and Its Analogues via a Multicomponent Assemblage

The total synthesis of sandramycin has been accomplished by using a Staudinger/aza-Wittig/diastereoselective Ugi three-component reaction sequence as a key step to obtain a linear pentadepsipeptide. Subsequent [5 + 5] coupling of the penptapeptide, macrolactamization, and introduction of the quinaldin chromophores afforded sandramycin. Dihydroxy and diacetoxy analogues were also prepared, and the cytotoxic activity of these analogues against a range of human cancer cell lines was evaluated

Pt–Cu Bimetallic Alloy Nanoparticles Supported on Anatase TiO₂: Highly Active Catalysts for Aerobic Oxidation Driven by Visible Light

Visible light irradiation (λ > 450 nm) of Pt–Cu bimetallic alloy nanoparticles (∼3–5 nm) supported on anatase TiO₂ efficiently promotes aerobic oxidation. This is facilicated <i>via</i> the interband excitation of Pt atoms by visible light followed by the transfer of activated electrons to the anatase conduction band. The positive charges formed on the nanoparticles oxidize substrates, and the conduction band electrons reduce molecular oxygen, promoting photocatalytic cycles. The apparent quantum yield for the reaction on the Pt–Cu alloy catalyst is ∼17% under irradiation of 550 nm monochromatic light, which is much higher than that obtained on the monometallic Pt catalyst (∼7%). Cu alloying with Pt decreases the work function of nanoparticles and decreases the height of the Schottky barrier created at the nanoparticle/anatase heterojunction. This promotes efficient electron transfer from the photoactivated nanoparticles to anatase, resulting in enhanced photocatalytic activity. The Pt–Cu alloy catalyst is successfully activated by sunlight and enables efficient and selective aerobic oxidation of alcohols at ambient temperature

Graphitic Carbon Nitride Doped with Biphenyl Diimide: Efficient Photocatalyst for Hydrogen Peroxide Production from Water and Molecular Oxygen by Sunlight

Photocatalytic hydrogen peroxide (H₂O₂) production from water and molecular oxygen (O₂) by sunlight is a promising strategy for green, safe, and sustainable H₂O₂ synthesis. We prepared graphitic carbon nitride (g-C₃N₄) doped with electron-deficient biphenyl diimide (BDI) units by a simple calcination procedure. The g-C₃N₄/BDI catalyst, when photoirradiated by visible light (λ >420 nm) in pure water with O₂, successfully promotes water oxidation by the photogenerated valence band holes and selective two-electron reduction of O₂ by the conduction band electrons, resulting in successful production of millimolar levels of H₂O₂. Electrochemical analysis, Raman spectroscopy, and ab initio calculation results revealed that, upon photoexcitation of the catalyst, the photogenerated positive holes are localized on the BDI unit while the conduction band electrons are localized on the melem unit. This spatial charge separation suppresses rapid recombination of the hole–electron pairs and facilitates efficient H₂O₂ production. The solar-to-chemical energy conversion efficiency for H₂O₂ production is 0.13%, which is comparable to that for photosynthetic plants. This metal-free photocatalysis therefore shows potential as an artificial photosynthesis for clean solar fuel production