Efficient methods for the synthesis of carboxylic esters and lactones using benzoic anhydrides by the promotion of Lewis acid or basic catalyst is accounted in this paper. Various carboxylic esters are prepared in high yields through the formation of the corresponding mixed anhydrides from 4-(trifluoromethyl) benzoic anhydride (TFBA) and carboxylic acids in the presence of Lewis acid catalyst. Several macrolactones and medium-sized lactones are also prepared from the corresponding hydroxycarboxylic acids by the combined use of TFBA and an acidic species under the mild reaction conditions. Furthermore, a variety of carboxylic esters or lactones are obtained at room temperature in excellent yields with high chemoselectivities from nearly equimolar amounts of carboxylic acids and alcohols, or hydroxycarboxylic acids using 2-methyl-6-nitrobenzoic anhydride (MNBA) with basic promoters. These methods are successfully applied to the synthesis of 8-membered ring lactone moieties of cephalosporolide D, and octalactins A and B.
Utilization of water as a reagent as well as a solvent is an important topic in synthetic organic chemistry. This article describes recent progress of hydration and hydrolysis reactions catalyzed by transition metal complexes. Direct transformation of 1-alkynes into aldehydes by Ru (II) -catalyzed hydration has been developed. It has been long known as a textbook example that the hydration follows Markovnikov's rule to give ketones as a sole product. Mechanistic study of the transformation revealed that Ru (II) -vinylidene complexes presumably are not involved in the current hydration reaction, but Ru (IV) -hydride-vinylidene complexes are concerned. Ru (II) -catalyzed hydroamination and its application to heterocycle synthesis are also described. This paper also illustrates metal catalyzed hydrolysis of terminal epoxides, alkenyl esters and ethers. Hydrolytic kinetic resolution of some chiral terminal epoxides and vinyl ethers are also developed.
Optically active γ-fluoroalkylated allylic alcohols were prepared via various synthetic protocols such as enzymatic resolution of the racemate, difluorocarbene-mediated reaction, and a novel 1, 3-allylic rearrangement of α-fluoroalkylcarbinols. Thus-obtained allylic alcohols could participate nicely in various sigmatropic rearrangements such as Johnson-, Eshenmoser-, Ireland-Claisen, and [2, 3] -Wittig shifts, to give the corresponding rearranged products with excellent stereoselectivity in good to high yields. The sequential operation of 1, 3-allylic shift and the following Ireland-Claisen rearrangement realized the one-pot synthesis of the multifunctionalized building blocks in high yields from easily accessible α-fluoroalkylated carbinols. The Ireland-Claisen products underwent iodolactonization and osmylation, γ-lactones with four successive chiral centers being afforded in a highly stereoselective manner.
Recent advance in molecular biology unveils novel physiological functions of prostanoid receptors. According to cDNA cloning and structural elucidation of the receptors, exploration research of new prostanoid receptor agonists and antagonists has been largely accelerated. Introduction of fluorine atoms into a series of prostanoid derivatives, often brought significant improvement in their physicochemical and pharmacological profiles. Newly designed fluorinated prostanoids are synthesized and developed in a broad range of therapeutic areas as medicines. The recent progress in the synthesis and pharmacological aspects of novel fluorinated prostaglandin derivatives is reviewed and discussed herein.
The increasing incidence of antibiotic resistance has brought a new sense of urgency to the discovery and development of antibacterial drugs. Globomycin (1a), a 19-membered cyclic depsipeptide, shows potent antibacterial activity against Gram-negative bacteria and has been proven to be a specific inhibitor of signal peptidase II, a prolipoprotein-processing enzyme. Although 1a is an important compound for studies on lipoprotein biosynthesis, its structure has been ambiguous for more than 20 years since its discovery. We have succeeded in determining the absolute structure of 1a by X-ray analysis, and developed the synthetic route for this compound and its various analogues. As a result of SAR studies, one of the analogues showed more potent activity against Gram-negative bacteria than 1a and also exhibited antibacterial activity against MRSA. In addition, a conformational analysis of 1a was performed by high-temperature molecular dynamics simulation in combination with 1H NMR analysis to elucidate the conformations in solution. The relative ratio of the major and minor isomers present, which differs depending on the solvent, was derived from their relative energy differences obtained by the conformational analysis. Details are described.
Peptide nucleic acid (PNA), which has been proposed by Peter E. Nielsen in 1991, is one of the most typical and successful synthetic nucleic acid model compound, called an artificial nucleic acid, with extremely attractive and excellent properties, such as exactly sequence selective binding not only to complementary DNA but also to RNA, highly chemical and biological stability, forming very tight and stable complex with complementary DNA and RNA, and so on. Still, PNA also shows same inherent and crucial drawbacks, such as low solubility against aqueous solution, low cell membrane permeability, and uncertain direction of DNA/RNA sequence recognition. Thus, in order to improve these properties, a number of PNA derivatives have been proposed. In this review paper, we would like to give an overview of these strategies and properties of PNA derivatives and present our proposed novel strategy for active external reversible control of DNA/RNA recognition with peptide ribonucleic acid, PRNA.