Search

Novel 2-iminiomethylvinamidinium trihalides were isolated as stable crystals and found to be useful triformylmethane synthons with non-deliquescent nature in air. They were easier to manufacture, handle, and store than the known 2-iminiomethylvinamidinium dichloride. By virtue of in situ aminal protection, a combination of the vinamidinium salt with a secondary amine achieved an efficient and scalable synthesis of 7-acylamino-3-formylquinoline, a versatile synthetic intermediate for potent anti-obesity drugs 7-acylamino-3-aminomethyl-8-methylquinolines.

Application of this method is demonstrated by the total syntheses of Kavain (IV) and Yangonin (V).

A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6-chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The SNAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100–110 °C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core.

The reaction of aldehydes and ketones with in situ generated zinc alkoxide tolerates a wide range of functional groups.

This review article describes preparation and modification of oligonucleotides by condensation in aqueous solution. Nucleotides and oligonucleotides are generally soluble in water, but not in organic solvents. Reactions in aqueous solution are therefore indispensable. Condensation in aqueous media is thermodynamically unfavorable. Several methods have been devised to overcome this problem. Large amount of water soluble condensing agents such as EDC or cyanogen bromide are employed for the condensation of oligonucleotides. Use of imidazole-activated nucleotides is an another approach for the preparation and the modification of oligonucleotides. The control of pH of the reaction media is necessary to accomplish the efficient and regioselective condensation. Metal ions or polynucleotide template, wihch organize the substrate nucleotides by complex formation promote the target condensation.

The coupling reaction of activated nucleobases, such as the sodium salts of N-benzoyladenine and 6-chloropurine and 2,4-bis-O-trimethylsilylthymine, with 1-α-chloro-2-deoxy-3,5-di-O-p-toluoylribofuranose (1) in a mixture of acetonitrile and tetrahydrofuran leads to the stereospecific formation of α-anomeric 2'- deoxynucleosides with satisfactory yields. The ratio of the distribution between the resulted α- and β-stereoisomers was about 3:1 in each case. The method is simple and applicable to the preparation of both purine and pyrimidine α-2'- deoxynucleosides

Arabinoaminooxazoline reacted readily with α-(bromomethyl)acrylate derivatives to afford the corresponding adduct. Potassium tert-butoxide- or sodium methoxide-catalyzed cyclization of the adduct gave 5-substituted 2,2′-anhydroarabinofuranosyluracil derivatives.

Electrochemical reduction of natural graphite was carried out in 1M LiClO[sub 4] ethylene carbonate (EC)/1,2-dimethoxyethane (DME) solution at 30 C. Natural graphite was reduced stepwise to LiC[sub 6]. The staging phenomenon was observed by X-ray diffraction (XRD). The first stage and the second stage compounds were identified as a commensurate structure in which lithium atoms form a close-packed two-dimensional array. A second-stage compound (LiC[sub 18]) with a different in-plane lithium ordering based on a LiC[sub 9] two-dimensional packing in lithium intercalated sheets also was observed; also third, fourth-stage compounds were identified. The electrochemical oxidation of the first-stage compound (LiC[sub 6]) was examined and shown to reversible over the entire range, i.e., C[sub 6] + xLi [r reversible] Li[sub x]C[sub 6]. The reaction mechanism for the reduction of graphite and the oxidation of the first-stage compound are discussed in relation to the staging phenomenon from the detailed open-circuit voltage and XRD data. The chemical potential of LiC[sub 6] was estimated to be [minus]3.6 kcal mol from the observed reversible potential. The feasibility of using a lithium-graphite intercalation compound in lithium ion (shuttlecock) cells is described, and the innovative secondary systems, C[sub 6]/LiCoO[sub 2] and C[sub 6]/LiNiO[sub 2] fabricated in discharged states,more » are demonstrated.« less

5-Substituted uracil nucleosides useful for the attachment of linker arms to nucleic acids are prepared from arabinoaminooxazoline and dimethyl α-bromomethylfumarate in a short reaction sequence without using any protecting groups, and incorporated into oligodeoxyribonucleotides.

2′-Deoxyuridine derivatives bearing several kinds of amino-linker arms at C5 position were synthesized from 5-(methoxycarbonylmethyl)-2′-deoxyuridine and ethylenediamine, 1,6-hexanediamine, or tris(2-aminoethyl)amine. The modified nucleosides were incorporated into oligodeoxyribonucleotides at one or three positions in place of thymidine residues. The thermal stability of the duplexes was investigated. Three incorporations of ethylenediamine or tris(2-aminoethyl)amine at the C5-position increase the duplex stability. The amino-linker arm affected the stability of the duplexes depending on the number of amino groups in the linker arm and the length of the arm. The linker arm improved the nuclease resistance at 5′-side phosphodiester linkage of the modified nucleoside in oligodeoxyribonucleotides.

Acridine-modified oligodeoxyribonucleotides (ODNs) at the C5-position of a 2′-deoxyuridine via different lengths of linker arms were synthesized. Reaction of 5-(N-aminoalkyl)carbamoylmethyl-2′-deoxyuridines with 9-phenoxyacridine gave the acridine-modified 2′-deoxyuridines which were incorporated into ODNs. The duplexes containing the acridine-modified strands and their complementary DNA or RNA were thermally more stable than that containing the unmodified strand. Thermal stability of the duplexes of the modified ODNs varied depending on the length of the linker arms. This paper is dedicated to the late Professor Tsujiaki Hata.

A novel 2′-deoxyuridine derivative bearing a cyanomethoxycarbonylmethyl group at the C-5 position (1) was synthesized, and its use was examined as a convertible nucleoside for the versatile post-synthesis functionalization of oligodeoxyribonucleotides (ODNs). The ODNs containing 1 reacted with primary monoamines such as heptylamine, histamine, and tyramine as well as d- and polyamines under mild conditions, giving the corresponding derivatized ODNs.

We have synthesized adenosine and 7-methylguanosine 5‘-diphosphate imidazolides from imidazole and the corresponding nucleoside 5‘-diphosphates. The phosphorimidazolide bond of the compounds was susceptible to hydrolysis and hydrolyzed gradually in neutral aqueous solution, but it was more stable than that of the corresponding imidazolides of nucleoside 5‘-monophosphate. The 7-methylguanosine 5‘-diphosphate imidazolide reacted with guanosine 5‘-monophosphate or 5‘-monophosphorylated oligoribonucleotides in neutral aqueous solution in the presence of an Mn2+ ion catalyst converting to the cap portion of mRNA or the capped m7Gppp-oligoribonucleotides in substantial yields. The condensation reaction of adenosine 5‘-diphosphate imidazolide with adenosine 5‘-monophosphate took place similarly in neutral aqueous solution by a divalent metal ion-catalyst such as Mg2+ or Mn2+, yielding diadenosine 5‘,5‘-triphosphate.

Potassium lespedezate (1) is the leaf-opening substance of a nyctinastic plant, Lespedeza cuneata G. Don. We have synthesized two sugar-derivatives of 1, potassium galactolespedezate (4) and mannolespedezate (6). Both 4 and 6 were quite effective for the leaf-opening of Cassia. mimosoides at 8 × 10−7 M, as strong as 1. However, 1 kept the leaf open only for a few days; on the other hand, 4 and 6 kept the leaf open after a week at that concentration. Additionally, remarkable difference was observed in the rate of enzymatic hydrolysis of natural and artificial leaf-opening sustance by using commercially available β-glucosidase Therefore, 4 and 6 would not be hydrolized in the plant body, and are potentially useful molecular probes for the studies of the control of the nyctinastic leaf-movement by a biological clock.

In a previous paper, the syntheses of potassium galactolespedezate (1) and potassium galactoisolespedezate (2), artificial leaf-opening substances useful for bioorganic studies of nyctinasty were reported. The fluorescent probe compounds, fluorescence-labeled galactoisolespedezates (3, 10, 13), designed on the basis of 1 and 2, were prepared. In particular, compound 3 was bioactive at 5×10−5 M, one-fiftieth as strong as the natural leaf-opening substance. This fluorescent probe would be useful for bioorganic studies of nyctinasty.

Two new diterpenoids, 2 and 4, having a dolabellane skeleton were isolated from the Okinawan soft coral of the genus Clavularia. Their structures were determined based on spectroscopic analysis, chemical conversion and X-ray crystallographic analysis. One of these diterpenoids showed cytotoxic activity against tumor cells.

An oligodeoxyribonucleotide (ODN) containing three C5-substituted arabinofuranosyluracils was synthesized by the post-synthetic modification method from the ODN containing three C5-substituted 2,2'-anhydrouridines. The stability of the modified ODN/DNA duplex was lower than that of the corresponding normal duplex but that of the modified ODN/RNA duplex showed little change. The modified ODN could induce RNase H activity and was resistant against nuclease.

A high-active oxygen reduction catalyst was prepared by heat-treatment of transition metal hexacyanometalate precursors containing cobalt and iron dispersed on carbon black under an inert atmosphere. The catalytic activity for oxygen reduction was insensitive to the presence of high concentration of methanol and was comparable to that of the platinum catalyst in the absence of methanol.

2'-Deoxy-2'-S-hexyluridine derivative was synthesized from 2,2'-anhydrouridine and 1-hexanethiol and incorporated into an oligodeoxyribonucleotide. The thermal stability of the duplexes formed by the 2'-S-hexyl modified ODN with either the complementary DNA or RNA strand was decreased compared to the unmodified counterparts.

Electrochemical and x-ray diffraction studies were carried out for the reduction of RuO 2 having rutile structure in 1M LiClO 4 propylene carbonate/1,2-dimethoxyethane (1:1) solution. RuO 2 was topotactically reduced to LiRuO 2 , drawing an L-shaped voltage curve