Kazuo Kamaike

An efficient method for the synthesis of [4-15N]cytidine and [6-15N]adenosine derivatives from uridine and inosine

Abstract Nucleophilic substitution reactions of 4-azolyl-1-β-D-ribofuranosylpyrimidin-2(1H)-one and 6-azolyl-9-β-D-ribofuranosyl-9H-purine derivatives, which were converted from uridine and inosine, with [15N]phthalimide in the presence of triethylamine or DBU were found to give [4-15N]-N4-phthaloylcytidine and [6-15N]-N6-phthaloyladenosine derivatives, respectively, in high yields, while reactions with succinimide also afforded N4-succinylcytidine and N6-succinyladenosine derivatives, in high yields.

An Efficient Method for the Synthesis of [4–15N]Cytidine, 2′-Deoxy[4–15N]Cytidine, [6–15N]adenosine, and 2′-Deoxy [6–15N]adenosine Derivatives # 1

Abstract Nucleophilic substitution reactions of 4-azolyl-1 β-P-D-ribofuranosylpyrimidin-2(1H)-one and 6-azolyl-9-β-D-ribofuranosyl-9H-purine derivatives, which were converted from uridine and inosine, with [15N]phthalimide in the presence of triethylamine or DBU gave N 4-phthaloyl[4-15N]cytidine and N 6-phthaloyl[6-15N]- adenosine derivatives, respectively, in high yields. Similar reactions of those azolyl derivatives with succinimide afforded N 4-succinylcytidine and N 6-succinyladenosine derivatives in high yields. The corresponding 2′-deoxyribonucleosides were also synthesized efficiently through the same procedure. 1. Partial Protection of Carbohydrate Derivatives. Part 31. For Part 30, see Aoyama, Y.; Sekine, T.; Iwamoto, Y.; Kawashima, E.; Ishido, Y. Nucleosides Nucleotides, submitted. The present work has partly been communicated (cf. Kamaike, K.; Takahashi, M.; Utsugi, K.; Tomizuka, K.;Ishido, Y. Tetrahedron Lett. 1995, 36, 91–94.). #This paper is dedicated to Dr. Yoshihisa Mizuno on the occasion ...

Efficient methods for the synthesis of [2-15N]guanosine and 2'-deoxy[2-15N]guanosine derivatives.

The nucleophilic addition–elimination reaction of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N 2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N 2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutyl-ammonium periodate. A similar sequence of reactions of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(β-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N 2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2′,3′,5′-tri-O-acetyl[2-15N]guanosine. The corresponding 2′-deoxy derivatives (16 and 18) were also synthesized through similar procedures.

Oligonucleotide synthesis by the use of a 2-(levulinyloxymethyl)-5-nitrobenzoyl group as the novel base-labile protecting Group for the 5′-hydroxyl groups of ribonucleoside and 2′-deoxyribonucleoside 3′-phosphoramidites

Abstract A novel 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) protecting group for the 5′ position of nucleoside 3′-phosphoramidites was successfully applied to the solid-phase synthesis of both an oligodeoxyribonucleotide (TpTpT and TpTpTpT) and an octaribonucleotide in combination with a 2′- O -Thp protecting group (UpCpApGpUpUpGpG). The LMNBz group was simply unmasked due to its base-labile property by a two-step procedure, i.e. , treatments with 0.5 M hydrazine hydrate in 1:4 acetic acid - pyridine, and then with 0.5 M imidazole in acetonitrile.

Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis

Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate.

Synthesis and analysis of nucleosides bearing pyrrolepolyamide binding to DNA.

Abstract An efficient synthesis of adenosine bearing pyrrolepolyamide 1 was achieved by coupling of 3 with 2. The CD spectra obtained at several [ligand ]/[duplex] ratios allowed verification of the formation complex of the DNA duplex [d(CGCAAATTGGC)/d(GCCAATTTGCG)] with 1.

Synthesis of an Oligonucleotide Bearing a Phosphate Function at the 5′-Terminus Using a Novel Protecting Group in Terms of a Cellulose Acetate Derivative as a Polymer-Support

Abstract Synthesis of the title oligonucleotide bearing a phosphate function at the 5′-terminus, i.e., pCpUpCpGpUpCpCpApCpCpA, by the use of the terminal cytidylic acid unit involving a novel protecting group of 2-[2-(monomethoxytrityloxy)ethylthio]ethyl group on its 5′-phosphoryl function in terms of a cellulose acetate polymer-support is described.

Synthesis and Evaluation of Pyrrole Polyamide- 2′-Deoxyguanosine 5′-Phosphate Hybrid

Pyrrole polyamide-2′-deoxyguanosine 5′-phosphate hybrid (Hybrid 4) was synthesized and evaluated in terms of the inhibition of mouse mammary carcinoma FM3A cell growth. Hybrid 4 was found to exhibit dose-dependent inhibition of cell growth.

Synthesis and evaluation of oligonucleotide-conjugated pyrrole polyamide-2'-deoxyguanosine hybrids as novel gene expression control compounds.

DNA oligonucleotide-conjugated pyrrole polyamide-2′-deoxyguanosine hybrids were synthesized and examined as novel gene expression control compounds. The Tm values and circular dichroism spectral analyses showed that the oligonucleotide-conjugated hybrids possess high DNA recognition and a very high binding affinity for DNA that includes the pyrrole polyamide binding sequence.

Novel Base-Labile Protecting Groups for 5′-Hydroxy Function in Solid-Phase Oligonucleotide Synthesis

Abstract The 6-(levulinyloxymethyl)-3-methoxy-2-nitrobenzoyl (LMMoNBz) and 2-(levulinyloxymethyl)-5-methoxy-4-nitrobenzoyl (LMMpNBz) groups were developed as novel base-labile protection for the 5′-hydroxy function in solid-phase oligonucleotide synthesis. A comparative study of the LMMoNBz, LMMpNBz and 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) protecting groups for oligonucleotide synthesis proved strong feasibility for the LMMoNBz group.