Synthesis and Properties of 4'-ThioLNA/BNA.

To develop a new nucleoside analogue applicable to oligonucleotide therapeutics, we designed a 4'-thio analogue of an LNA/BNA monomer. Synthesis of 4'-hydroxymethyl-4'-thioribonucleoside was achieved by a tandem ring-contraction-aldol reaction of a 5-thiopyranose derivative and the subsequent Pummerer-type thioglycosylation reaction of the corresponding sulfoxide. Treatment of 4'-hydroxymethyl-4'-thiopyrimidine nucleosides with diphenyl carbonate in the presence of catalytic NaHCO3 gave the desired 4'-thioLNA/BNA monomers, which were introduced into oligonucleotides.

Palladium-Catalyzed Three-Component Coupling of Ynamides.

A palladium-catalyzed regioselective three-component coupling of ynamides was developed. The reaction proceeded smoothly to furnish the desired products when carried out at 70 °C in acetonitrile/water with potassium carbonate in the presence of 2.5 mol % Pd2(dba)3·CHCl3 without a ligand. Various iodides and boronic acids were used in this reaction, and a carbon-carbon bond was formed with satisfactory regioselectivity from the ynamides.

Synthesis of 2'-aminouridine derivatives as an organocatalyst for Diels-Alder reaction.

To develop a novel asymmetric organocatalyst based on a ribonucleoside skeleton, we designed and synthesized 2'-aminouridine derivatives. The synthesized 2'-aminouridines having bulky substituents at both base and sugar moieties could catalyze the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene. However, the optical purities of the resulting products were unexpectedly low.

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates.

To synthesize nucleoside and oligosaccharide derivatives, we often use a glycosylation reaction to form a glycoside bond. Coupling reactions between a nucleobase and a sugar donor in the former case, and the reaction between an acceptor and a sugar donor of in the latter are carried out in the presence of an appropriate activator. As an activator of the glycosylation, a combination of a Lewis acid catalyst and a hypervalent iodine was developed for synthesizing 4'-thionucleosides, which could be applied for the synthesis of 4'-selenonucleosides as well. The extension of hypervalent iodine-mediated glycosylation allowed us to couple a nucleobase with cyclic allylsilanes and glycal derivatives to yield carbocyclic nucleosides and 2',3'-unsaturated nucleosides, respectively. In addition, the combination of hypervalent iodine and Lewis acid could be used for the glycosylation of glycals and thioglycosides to produce disaccharides. In this paper, we review the use of hypervalent iodine-mediated glycosylation reactions for the synthesis of nucleosides and oligosaccharide derivatives.

Synthesis of 4'-Thionucleosides as Antitumor and Antiviral Agents.

Many attempts have been made to synthesize structurally novel nucleoside derivatives in order to identify effective compounds for the treatment of tumors and virus-caused disease. At our laboratories, as part of our efforts to synthesize 4'-thionucleosides, we have identified and characterized biologically active nucleosides. During the course of our synthetic study, we developed the Pummerer-type thioglycosylation reaction. As a result, we synthesized a potent antineoplastic nucleoside, 1-(2-deoxy-2-fluoro-ß-D-4-thio-arabino-furanosyl)cytosine (4'-thioFAC), and several novel 4'-thionucleosides that possess antiherpes virus activities.

Practical Synthesis of 4'-Thioribonucleosides from L-Arabinose via Novel Reductive Ring-Contraction Reaction and Pummerer-Type Thioglycosylation.

The detailed practical synthesis of 4'-thionucleosides starting from L-arabinose is described here. 1,4-Anhydro-2,3-O-isopropylidene-4-thioribitol, which is the key intermediate for the synthesis of 4'-thionucleosides, is obtained from L-arabinose in several steps, including a novel reductive ring-contraction reaction. After oxidation of the key intermediate, the sulfoxide is subjected to Pummerer-type thioglycosylation in the presence of persilylated nucleobases to obtain the 4'-thioribonucleosides in good yield and ß-selectively. © 2017 by John Wiley & Sons, Inc.

A facile synthesis of fully protected meso-diaminopimelic acid (DAP) and its application to the preparation of lipophilic N-acyl iE-DAP.

Synthesis of beneficial protected meso-DAP 9 by cross metathesis of the Garner aldehyde-derived vinyl glycine 1b with protected allyl glycine 2 in the presence of Grubbs second-generation catalyst was performed. Preparation of lipophilic N-acyl iE-DAP as potent agonists of NOD 1-mediated immune response from 9 is described.

Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)-quinolones acting as dienophiles.

Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives were carried out to give the phenanthridone derivatives under both atmospheric and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)-quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined using molecular orbital (MO) calculation.

Novel Diels-Alder reaction of 4-nitro-1(2H)-isoquinolones.

A novel Diels-Alder (DA) reaction with 4-nitro-1(2H)-isoquinolones acting as the dienophile afforded 5(6H)-phenanthridone derivatives. The DA reaction of 4-nitro-1(2H)-isoquinolone with 1-methoxy-1,3-butadiene gave biologically active 5(6H)-phenanthridone possessing in a high yield. Regioselectivity of 4-nitro-1(2H)-isoquinolones with 1-methoxy-3-silyloxy-1,3-butadiene was calculated using molecular orbital (MO) calculations.

Synthesis of isoquinoline derivatives using ROM-RCM of cyclobutene-yne.

Isoquinoline derivatives were synthesized from cyclobutenylmethylamine derivatives having an alkyne moiety in a tether using a second-generation ruthenium carbene complex under ethylene gas in good yields.

Improved computed radiography image quality from a BaFl:Eu photostimulable phosphor plate.

Recent advances in the design of photostimulable phosphor (PSP) plates for computed radiography (CR) systems have made it possible to manufacture plates made of BaFI:Eu phosphor material in the cassette form. The image quality of this plate, six BaF(Br,I):Eu plates, and one BaFBr:Eu plate were evaluated in terms of presampling modulation transfer function (MTF), normalized Wiener spectra (WSN), and detective quantum efficiency (DQE). Compared with the best-performing BaF(Br,I):Eu plate, the BaFI:Eu plate provided DQE that was higher, at spatial frequencies of 0.5, 1.0, and 2.0 cycles/mm, by 12% (21.8 versus 19.4), 13% (18.8 versus 16.7), and 11% (12.0 versus 10.8), respectively. Since presampling MTF values of the two plates were comparable, the BaFI:Eu plate's higher DQE is attributable to total WSN conversely being lower by 17% [8.65 x 10(-5) (mm2) versus 10.38 x 10(-5) (mm2)], 17% [5.85 x 10(-5) (mm2) versus 7.03 x 10(-5) (mm2)], and 12% [2.82 x 10(-5) (mm2) versus 3.19 x 10(-5) (mm2)] at the specified frequencies, respectively, primarily due to the contribution of x-ray quantum WSN. This jibes with the high x-ray absorption provided by the 27%-higher x-ray attenuation coefficients (7.54 versus 6.07, at 60 KeV) that BaFI offers over BaF(Br(0.85),I(0.15)), a result of the high atomic number of BaFI's exclusively iodine halide content. The results were consistent with earlier studies of several of these same plates and indicate that BaFI:Eu is a promising avenue to lower image noise and higher overall CR system image quality.