N,N-Dialkyl-substituted propargylic amines undergo various transformations in the presence of transition-metal catalysts: The hydride-transfer reaction in the presence of palladium catalysts to afford the corresponding allenes, the fragment-exchange reaction with amines or acetylenes in the presence of copper(I) catalysts through C(sp)-C(sp3) bond cleavage, and the redox cross-dehydrogenative coupling in the presence of zinc(II) catalysts to afford N-tethered 1,6-enynes. In all the above cases, the generation of iminium intermediates, which would be assisted by a lone pair on the nitrogen atom of the propargylic amines, is essential for further transformations.
The development of new efficient bond-forming reactions is important in synthetic organic chemistry. Recent developments concerning the synthetic methods utilizing highly electrophilic Michael acceptors, ethenetricarboxylates are described. Ethenetricarboxylate is a member of methylenemalonates and more reactive than alkylidenemalonates by the electron-withdrawing effect of 2-ester group. In particular, Lewis acids promote the reactions of ethenetricarboxylate derivatives efficiently. Various nucleophiles could undergo conjugate additions and the further bond-forming reactions. The high functionalization of the products may be useful for further elaboration. This paper describes catalytic Friedel-Crafts/Michael addition reactions of indoles, conjugate addition of amines, and various cycloadditions with compounds such as propargyl amines/alcohols, aminobenzaldehydes, and allenes in the presence of Lewis acid to give nitrogen and oxygen-containing heterocyclic and carbocyclic compounds. One-pot reactions with compounds such as aminoalcohol and Huisgen zwitterion in the absence of Lewis acids lead to various heterocyclic compounds. Lewis acid-promoted intramolecular cyclization reactions of functionalized ethenetricarboxylate derivatives has also been described.
The incorporation of fluorine into heterocyclic compounds has a great impact on the electron distributional profile to change the character of permanent dipole moment, pKa constant of heteroatoms and hydrogen bonding pattern. The technique has been often used for drug discovery process to control pharmacological properties of the parent compounds. Fluorinated β-lactams, aziridines and α,β-unsaturated-δ-lactones are considered as important motifs possible to modify their enzyme inhibition activity. Fluorinated quinolines are understood as privileged structure of antibacterial, antimalarial and anti-inflammatory medicines. These fluorinated heterocycles are now becoming the topics of recent organic synthesis and medicinal chemistry, while the synthetic approaches remain challenging. In this paper, we would like to introduce our recent progress to exploit such approaches for the fluorinated bioactive heterocycles by the use of ethyl bromodifluoroacetate, ethyl dibromofluoroacetate and fluorine-containing vinylsilanes.
Anthracene is one of the planar polyaromatic compounds with intriguing reactivities and properties so that the unit has been widely used to construct functional molecules and molecular assemblies through covalent and non-covalent linkages. The intrinsic features of the embedded anthracenes often interact to engender unique chemical behaviors and physical properties in multiple anthracene assemblies. This review article focuses on the preparation of novel three-dimensional nanostructures with tube, bowl, and capsule shapes, providing well-defined cavities encircled by anthracene shells. Interestingly, most of them showed unusual structural, emissive, and/or host properties.
Target-guided synthesis (TGS) is the method to allow target enzymes to synthesize their own inhibitors. The inhibitors identified by TGS are expected to show strong activity and high target-selectivity because they are synthesized by a specific reaction and/or in specific pockets of a target enzyme. Therefore, this approach would be useful for discovering novel selective enzyme inhibitors. Thus far, we found various enzyme inhibitors by means of TGS, i.e. (i) histone deacetylase (HDAC), human sirtuin (SIRT) and lysine-specific demethylase 1 (LSD1) inhibitors designed based on the enzymatic reaction mechanisms, (ii) LSD1 inactivators designed based on a direct target-drug delivery system and (iii) an HDAC8 inhibitor identified by in situ click chemistry utilizing an HDAC8/copper complex as a template. Here we present the design, synthesis, biological evaluation and inhibition mechanism analysis of these inhibitors.
A series of our studies on the chemical and genetic diversity of Ligularia species in the Hengduan Mountains area of China is reviewed. Diversities were detected in various species in terpenoid compositions and DNA sequences of the ITS region. Furanoeremophilanes were isolated from many species together with eremophilan-8-ones. Samples of some species such as L. virgaurea were grouped into two or more chemotypes, while L. cymbulifera and L. cyathiceps were uniform. Complex diversity was found in L. kanaitzensis. A hypothesis that the production of furanoeremophilanes is ecologically advantageous was proposed. Production of terpenoids in L. duciformis and related species were suggested to be acquired by hybridization which may be one of the major pathways of the evolution of Ligularia. Some taxonomically close species, such as L. lamarum and L. subspicata, were indistinguishable in both the root chemicals and the ITS sequences.
Metal-catalyzed organic reactions in live cell have been reported over the last decade, which also enabled imaging of the cell. These examples include removal of Alloc group, reduction of azide group and intermolecular cross-coupling.
Nitroso compounds have drawn much attention of synthetic organic and biological chemists because of their usefulness as synthetic intermediate as well as interesting bioactivity. Here, a recent report about the simple and selective preparative method for nitrosoarenes using nitrosonium tetrafluoroborate is described. It provides versatile nitrosoarenes including heteroarenes which are not easily prepared by alternative method.