Tohru Ueda

A facile one-step synthesis of 5′-phosphatidylnucleosides by an enzymatic two-phase reaction.

Abstract Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from phosphatidylcholines to the 5′-hydroxyl group of nucleosides in a two-phase system. A variety of 5′-phosphatidylnucleosides were easily prepared in high yields by this reaction.

A novel stereospecific radical cyclization of 2',3'-O-isopropylideneuridine and -adenosine 5'-aldehyde to the corresponding 6,5'-cyclodihydrouridine and 8,5'-cycloadenosine derivatives

Abstract Treatment of 2′,3′- O -isopropylideneuridine 5′-aldehyde with tributyltin hydride in the presence of azobisisobutyronitrile affords (6 S ,5′ S )-6,5′-cyclo-5,6-dihydro-2′,3′- O -isopropylideneuridine in a stereospecific manner. A similar reaction with N 6 -benzoyl-2′,3′- O -isopropylideneadenosine 5′-aldehyde leads to the corresponding 8,5′-cycloadenosine.

Nucleosides and Nucleotides. 104. Radical and Palladium-Catalyzed Deoxygenation of the Allylic Alcohol Systems in the Sugar Moiety of Pyrimidine Nucleosides§,1

Abstract New methods for the synthesis of 2′,3′-didehydro-2′,3′-dideoxy-2′ (and 3′)-methyl-5-methyluridines and 2′,3′-dideoxy-2′ (and 3′)-methylidene pyrimidine nucleosides have been developed from the corresponding 2′ (and 3′)-deoxy-2′ (and 3′)-methylidene pyrimidine nucleosides. Treatment of a 3′-deoxy-3′-methylidene-5-methyluridine derivative 8 with 1,1′-thiocarbonyldiimidazole gave the allylic rearranged 2′,3′-didehydro-2′,3′-dideoxy-3′-[(imidazol-1-yl)carbonylthiomethyl] derivative 24. On the other hand, reaction of 8 with methyloxalyl chloride afforded 2′-O-methyloxalyl ester 25. Radical deoxygenation of both 24 and 25 gave 26 exclusively. Palladium-catalyzed reduction of 2′,5′-di-O-acetyl-3′-deoxy-3′-methylidene-5-methyluridine (32) with triethylammonium formate as a hydride donor regioselectively afforded the 2′,3′-dideoxy-3′-methylidene derivative 35 and 2′,3′-didehydro-2′,3′-dideoxy-3′-methyl derivative 34 in a ratio of 95:5 in 78% yield. These reactions were used on the corresponding 2′-deoxy-2...

Ultraviolet absorption, circular dichroism and magnetic circular dichroism studies of sulfur-containing nucleic acid bases and their nucleosides

Abstract Spectroscopic studies on electronic structures were carried out for sulfur-containing nucleic acid bases, 2-thiouracil, 4-thiouracil, 2,4-dithiouracil and 2-thiocytosine along with their nucleosides. The absorption, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra were interpreted in terms of tautomerism to suggest that 4-thiouracil is in a 2-keto-4-thione form and the other bases exist as an equilibrium mixture of thione and thiol forms in solution. The π-π★ transition energies of the thione structures of 2-thiouracil, 2-thiocytosine and their nucleosides are almost the same as those of unsubstituted pyrimidine bases and nucleosides. The n-π★ transition from a 2-thione function was clearly detected as a negative CD band at about 320 nm. On the other hand, from the absorption, CD and MCD spectra, the transitions of the 4-thiouracil derivatives were found to take place in an energy region lower than those of the corresponding parent bases.

Chemical Conversion of Uridine to 3′-Branched Sugar Nucleosides (Nucleosides and Nucleotides. 421.)

Abstract Deamination of 1-(3-amino-3-deoxy-β-D-glucopyranosyl)-uracil gave a ring contracted nucleoside, 3′-deoxy-3′-formyluridine as a hemiacetal form, and uracil. Similar treatment of the 2′-deoxyderivative, 1-(3-amino-2,3-dideoxy-β-D-glucopyranosyl)uracil, gave the corresponding 2′,3′-dideoxy-3′-formyluridine in high yield. The 3′-epimerization of the 3′-formyluridine derivative was achieved and after reduction of the formyl groups, 2′,3′-dideoxy-3′(R and S)-hydroxymethyluridine were obtained.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF BRANCHED CHAIN-SUGAR NUCLEOSIDES1

Abstract 2′-Alkyl derivatives of cytidine and thymidine have been synthesized. 2′-Deoxy-6,2′-methanocytidine has also been prepared. Among them, 2′-deoxy-2′-methylidene-cytidine exhibited potent antitumor activities.

Synthesis and Biological Activities of 3′-Deoxy-3′-Isocyano, -Isothiocyano, and -Isoselenocyano-thymidines

Abstract 2′,3′-Dideoxy-3′-isothiocyano, -isocyano, and -isoselenocyanothymidines (6b, 8b, and 9) were synthesized from the corresponding 3′-amino derivatives (5a, b). These nucleosides were tested for inhibitory activity of the pathogenicity of HIV-1 and the growth inhibitory activity of mouse and human cancer cell lines.

Synthesis of 2′-C-Nitromethyl Derivatives of Uridine and the Structure of a Carbon-Bridged Cyclonucleoside Derived Therefrom (Nucleosides and Nucleotides 51)

Abstract Treatment of a 2′-ketouridine with a nitromethyl carbanion afforded a 2′-C-nitromethyl derivative which was deprotected to give 2′-C-nitromethyl-β-D-arabinosyluracil. A 2′-C-nitromethylarabinosyl-5-bromouracil was converted to a carbon-bridged cyclonucleoside through the 2′-nitromethylene derivative by treatment with sodium borohydride and DBU. A mechanism for this conversion was presented.

Mechanism of inactivation of tobacco mosaic virus with ozone

Abstract The inactivation mechanism of tobacco mosaic virus (TMV) in a phosphate buffer (pH 6.9) by ozone was studied. We previously reported that the damage of naked TMV-RNA occurred at the guanine moiety of RNA (Shinriki et al., Biochim. biophys. Acta655, 323, 1981). In this paper, we clarified the mode of the inactivation of TMV by using tritium-labeled TMV (TMV∗) prepared by the reconstitution of tritium-labeled TMV-RNA (TMV-RNA∗) and coat protein of TMV. It was found that the amount of extracted TMV-RNA∗ from ozone-treated TMV∗ decreased with the advance of ozonization, and that there was good correlation between the loss of infectivity and the decrease of recovery of TMV-RNA∗. When TMV lost its infectivity due to ozone, tryptophan and tyrosine of the coat protein were also degraded by ozone. Polyacrylamide gel electrophoretic analysis of the substance produced during ozonization showed that the coat protein subunits were aggregated with each other and cross-linked with TMV-RNA∗. From these results, it was concluded that the inability of uncoating is the major cause of the TMV inactivation by ozone.

A Lithiation Route to C-5 Substitution of an Imidazole Nucleoside and Its Application to the Synthesis of 3-Deazaguanosine.

Abstract Lithiation of a protected methyl 2-chloro-l-(β-D-ribofuranosyl) imidazole-4-carboxylate with LDA affords the C-5 anion which reacts with a wide range of electrophiles to provide various types of 5-substituted derivatives. Application of this method to the synthesis of 3-deazaguanosine, an antiviral nucleoside, is also described.