著者

菅原 徹 David G. CORK

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.55, no.5, pp.466-473, 1997-05-01 (Released:2009-11-16)

参考文献数

38

被引用文献数

3 4

---

Organic synthetic chemistry utilises scientific technology from various fields but compared to the great advances seen in the automation of analytical instruments over the last 20 years, the synthesis of organic compounds has been relatively slow to move from a largely manual process. Automation of synthesis is not only important for increasing efficiency, precision and safety but also decreasing labor and exploring new synthetic methodologies. In this review of automated synthesis apparatus we broadly divide them into two categories;those using robotic transfer of a reagent, reactant, product or vessel, and others that only use flow-lines for transfers between fixed reactors. These categories are then sub-divided into systems and workstations according to the extent of the operations and functions. We highlight some of the representative past and present automated synthesis apparatus and look at what the future may hold in the way of miniaturized and high-throughput automated synthesis.

著者

谷口 陽祐 佐々木 茂貴

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.62, no.10, pp.1026-1037, 2004 (Released:2009-11-13)

参考文献数

33

被引用文献数

2 4

---

Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules, and would become powerful tools for genomic research. However, the problem that the stable triplexes form only with homopurine : homopyrimidine sequences has not been generally solved in spite of extensive studies. In this study we have developed new base analogs (WNA) constructed of three parts, a benzene ring, a heterocyclic ring, and a bicyclic skeleton to hold these two parts. Among a number of WNA analogs, we have determined two useful WNA analogs, WNA-/βT and WNA-/βC, for selective stabilization of triplexes at a TA and a CG interrupting site with higher stability than the natural-type triplexes, respectively. The results of this study will provide useful information for the design of new WNA analogs to overcome inherent problems for further expansion of triplex recognition codes.

著者

尾崎 広明 〓原 正靖 澤井 宏明

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.62, no.12, pp.1238-1248, 2004-12-01 (Released:2009-11-13)

参考文献数

71

被引用文献数

1 2

---

Our recent study on the oligodeoxyribonucleotide (ODN) containing 5-substituted pyrimidine nucleosides is described. 5-Substituted 2 '-deoxyuridine derivatives and 5-substituted arabinofuranosyluracil derivatives were synthesized from 2, 2 '-anhydro-5-methoxycarbonylmethyluridine, which was synthesized from arabinoaminooxazoline and dimethyl α-bromomethylfumarate. Modified ODNs bearing these nucleoside analogs were prepared chemically by pre-synthetic modification method or post-synthetic modification method. Effect of 5-substituent groups on DNA/DNA or DNA/RNA duplexes was investigated by measuring the melting behaviors. Some of these modified ODNs are expected as antisense ODNs since these could induce RNase H activity and impart stability against nuclease. Also, 5-substituted 2 '-deoxyuridine analog triphosphates served as substrates of thermophilic family B DNA polymerases in a primer extension reaction or PCR, to give the modified ODNs. 5-Methoxycarbonylmethy1-2'-deoxyuridine residues incorporated into DNA by PCR could be used to post-synthetic derivatization. This finding is useful for in vitro selection of the functionalized DNA.

著者

高久 洋

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.40, no.12, pp.1159-1170, 1982-12-01 (Released:2009-11-13)

参考文献数

52

被引用文献数

1 2

---

The synthesis of oligonucleotides by the use of 5-chloro-8-quinolyl group has been described. This group can be successfully used as a phosphate protecting group of internucleotidic bonds in the synthesis of oligonucleotides by the phosphotriester approach. A new condensing and phosphorylating reagents are also described in detail.

著者

高久 洋

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.45, no.3, pp.196-211, 1987-03-01 (Released:2009-11-13)

参考文献数

167

被引用文献数

1 3

---

The phosphorylation of nucleosides is a fundamental reaction in the synthesis of oligonucleotides. This article reviews recent results on the phosphorylation of nucleosides in the synthesis of oligonucleotides by the phosphotriester method and the phosphite triester method. The new condensing and phosphorylating reagents for modified phosphotriester method, activated phosphotriester method, and modified phosphite triester method were discussed.

著者

小林 正治 平間 正博

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.62, no.3, pp.184-193, 2004-03-01 (Released:2009-11-13)

参考文献数

25

被引用文献数

3 4

---

A novel nine-membered enediyne antibiotic N 1999-A 2 was chemically synthesized and its absolute stereochemistry was determined. Chemical evidence of the thiol-triggered activation as well as the DNA cleavage profiles of N 1999-A 2 and its stereoisomers proved that the configuration of the C 11-naphthoate moiety played a dominant role in governing not only the orientation of the thiol attack but also the specificity of DNA cleavage.

著者

中谷 和彦 齋藤 烈

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.59, no.7, pp.670-679, 2001-07-01 (Released:2010-01-22)

参考文献数

52

被引用文献数

1 1

---

In order to gain insight into molecular basis for the sequence selective guanine alkylation by natural products aflatoxin B1 oxide and kapurimycin A3 we have synthesized epoxides with napthopyranone and anthrapyranone rings. Alkylation of guanine in DNA by these models proceeds with sequence selectivity similar to those of natural products. Absolute configuration of the epoxide side chain is significantly effective for the efficiency of guanine alkylation. Guanine alkylation most effectively proceeded at Gs in GG sequence, but G in the GC sequence was the least reactive site for the alkylation. The order of calculated energy levels of highest occupied molecular orbital (HOMO) for dinucleotide base pairs were in a good agreement with the G alkylation susceptibility experimentally obtained by our synthetic models. With these data we concluded that interaction of HOMO of DNA and LUMO of drugs is responsible for the sequence selectivity of guanine alkylation.

著者

橋本 祐一 首藤 紘一

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.43, no.10, pp.908-920, 1985 (Released:2009-11-13)

参考文献数

49

被引用文献数

2

---

Bis-intercalators and hemin-intercalators (Hemin-Glu-P-1's) which recognize and/or cleave DNA were designed and synthesized. 2-Aminodipyrido [1, 2-a : 3', 2' -d] imidazoles (Glu-P's) which are potent muta-carcinogens isolated from a pyrolysate of L-glutamic acid were used as intercalator moieties. Bis-intercalators possess extremely high affinity toward double stranded DNA and stabilize the double helix structure of DNA from heat denaturation effectively. Hemin-Glu-P-1's cleaved DNA at G-C and G-T sequences preferentially. Glu-P-1 moiety which recognizes DNA by intercalation and a functional group which can be an intramolecular fifth ligand of the ferrous ion in the hemin moiety are required for strong DNA-cleaving ability. The mode of DNA-cleaving reaction of Hemin-Glu-P-1's is quite similar to that of bleomycin (BLM). In other words, Hemin-Glu-P-1's are functional analogs of BLM. The mechanism of DNA cleavage by Hemin-Glu-P-1's and by BLM is not single. One of the mechanisms involves two bases elimination from the DNA.

著者

板東 俊和 杉山 弘

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.63, no.10, pp.1016-1027, 2005 (Released:2009-11-13)

参考文献数

43

被引用文献数

1 4

---

Fifty years after the discovery of the double helical structure of DNA, the complete sequence of the human genome has been determined. All genetic information, which is necessary for life, is written in 30 billion base pairs of DNA. Many diseases, including cancer, hereditary and viral diseases, can be understood at the DNA sequence level. Local DNA conformations are thought to play an important role in biological processes such as gene expression. Therefore, DNA sequences and local DNA conformation are targets of novel drugs that would precisely switch certain genes on or off. Modified bases that perform various functions can also be incorporated into defined DNA sequences. Since DNA can be amplified by PCR and in other organisms, DNA becomes a promising unit for nanotechnology applications. In this review, we focus on the sequence and conformation-specific chemical reactions that occur in DNA, and the prospective uses of the chemical biology of DNA will be discussed.

著者

飯田 博一 杉山 弘

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.58, no.10, pp.975-987, 2000 (Released:2009-11-13)

参考文献数

39

被引用文献数

2 3

---

By the completion of the human genome project, many diseases including cancer, hereditary and viral diseases can be understood by the DNA sequence level. Control of the specific gene expression will provide ultimate gene therapy. Minor groove binding polyamides containing N-methylpyrrole and N-methylimidazole amino acids exhibit promising performance based on the recognition of nucleic acid sequences. Various types of sequence-specific DNA binding agents are developed and used for the regulation of gene expression. We synthesized novel type of polyamide-alkylator conjugates. These synthetic compounds alkylated predetermined DNA sequences selectively, and also some of them possessed selective potency for certain cancer cell lines. In this review, we will focus on recent progress of minor groove binding polyamides that play important roles in the rational recognition of nucleic acid sequences. One of the future directions of rational design of molecular medicine in the post genome era is proposed.

著者

長瀬 敏雄

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.57, no.10, pp.888-897, 1999 (Released:2009-11-16)

参考文献数

40

被引用文献数

1 1

---

Medicinal chemistry efforts on optimization of the endothelin receptor antagonistic natural products toward highly potent and selective ETA, ETB or ETA/B dual receptor antagonists are summarized. In order to get adequate biological tools for elucidating physiological and/or pathophysiological roles of endothelin as well as to identify highly potent antagonists possessing appropriate profiles, liquid phase and solid phase peptide synthesis, and their modification have been carried out. During these efforts, we have realized physiological roles of endothelin and its receptors, and have confirmed drug discovery values of its receptor antagonists as clinical drugs to modulate various kinds of disease.

著者

大久保 満

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.55, no.6, pp.566-569, 1997-06-01 (Released:2009-11-16)

参考文献数

10

被引用文献数

2 3

---

A new indolocarbazole anticancer agent, NB-506 (6-N-formylamino-12, 13-dihydro-1, 11-dihydroxy-13-β-D-glucopyranosyl) -5H-indolo [2, 3-a] pyrrolo [3, 4-c] carbazole-5, 7 (6H) -dione) was developed. The total synthesis of NB-506 was successfully achieved with a new glycosylation reaction which was carried out in good yield with high β-selectivity. Moreover the Mitsunobu reaction was newly found to be a convenient method for synthesizing dissymmetric indolocarbazole glycosides at the glycosylation step.

著者

長瀬 博 藤井 秀明

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.64, no.4, pp.371-381, 2006-04-01 (Released:2010-10-20)

参考文献数

30

被引用文献数

1 3

---

A selective nonpeptidic δ opioid receptor agonist TAN-67, (4aS*, 12 aR*) -4 a- (3-hydroxyphenyl) -2-methyl-1, 2, 3, 4, 4 a, 5, 12, 12 a-octahydropyrido [3, 4-b] acridine was designed from the selective δ opioid receptor antagonist NTI on the basis of the message-address concept and the accessory site theory. (-) -TAN-67 is a potent and selective δ1 opioid receptor agonist and showed profound antinociceptive effect, cardioprotective effect, and antiarrhythmic effect. On the contrary, (+) -TAN-67 induced hyperalgesia, which is the opposite effect of the antinociception. Optical resolution of racemic TAN-67 and the synthesis of (4aS*, 8 aR*) -4 a- (3-methoxyphenyl) -2-methyl-6-oxodecahydroisoquinoline, the important intermediate ketone of TAN-67 synthesis were also described.

著者

奥山 彬

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.60, no.8, pp.794-799, 2002-08-01 (Released:2009-11-13)

参考文献数

8

被引用文献数

1

---

The key issue of the present drug development is to find the lead compound in the minimum time and cost by using all kinds of new and traditional technology such as genomic drug discovery, random High Throughput Screening (HTS), virtual screening, combinatorial chemistry, X-ray crystal analysis, molecular modeling and so on. It is crucial to build up efficiently Chemical Compound Library with wide diversity to be applied to HTS for any kind of biological activity. University Compound Project at Foundation for Education of Science and Technology was started on February 2002, to use more efficiently not commercially-available domestic and abroad University Compounds (UC) for the drug development by building up the University Compound Data Base (UCDB). So far, 60 chemists at 35 universities and institutes, and 12 companies have joined to the project. The project has collected about 29, 000 UCDB available to the participating companies for the selection of UC and would add about 10, 000 UCDB every year.

著者

石黒 正路 今城 精一

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.54, no.5, pp.427-436, 1996-05-01 (Released:2009-11-16)

参考文献数

30

被引用文献数

2 2

---

Complex structures of neocarzinostatin (NCS) and β-lactamase/β-lactam antibiotics were built using NMR and crystallographic data of the proteins. On binding of ligands to proteins, particular amino acid side chains as well as ligands show dynamic character to exhibit specific molecular recognition. NMR studies and conformational analysis of the Phe 78 side chain of NCS revealed that the Phe 78 residue plays a major role on the chromophore binding through conformational change of the side chain aromatic moiety. Crystal structures and computational modeling of the enzyme-ligand complexes indicated that at the active site, the carboxylate of β-lactam antibiotics induces the conformational change of the Lys 73 residue and acts as a trigger of the hydrolytic reaction (acylation). Modeling of the acyl-enzyme structures also suggested the role of a mobile water molecule at the active site for deacylation. Experimental (NMR and X-ray crystallography) and computational results provided a fruitful information about molecular interaction between proteins and ligands.

著者

石黒 正路 今城 精一

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.42, no.8, pp.722-731, 1984-08-01 (Released:2009-11-13)

参考文献数

52

被引用文献数

1 1

---

Recent application of three dimensional computer graphics technics has widely expanded to molecular modeling. This article describes a brief history of computer graphics use in molecular modeling, function of hardware and software and its application to molecular modeling in Suntory computer aided drug-design system.

著者

芝 哲夫

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.50, no.12, pp.1070-1073, 1992-12-01 (Released:2009-11-16)

被引用文献数

1

著者

端早田 隆

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.65, no.7, pp.715-716, 2007-07-01 (Released:2010-10-20)

参考文献数

11

被引用文献数

1 2

---

This short review describes the recent development on β-mannosidic bond formation. Though the formation of β-mannoside is rather difficult in chemical synthesis, following two useful representative methods are reported; 1) introducing an acetal moiety as an acceptor on a donor as the stereocontroling element for intramolecular β-mannosylation; 2) using a donor having cyclic acetal protecting group at O-4, 6 position. As for the later, it was reported that the introduction of propagyl group at O-2 position improved β-selectivity even if a donor having steric protecting group at O-3 position was employed. Catalytic and β-selective mannosylation is also noted.

著者

中野 眞汎

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.42, no.7, pp.665-671, 1984-07-01 (Released:2009-11-13)

参考文献数

18

被引用文献数

5 7

---

Poly (ethylene carbonate), poly (propylene carbonate), and poly (ethylene propylene carbonate) were examined as to their biodegradability, permeability, and drug release characteristics.Poly (ethylene carbonate) degraded but poly (propylene carbonate) did not in the peritoneal cavity of rats and the peritoneal cavity and subcutaneous tissue of guinea pigs. Mixtures of the two polymers degraded at a rate in proportion to poly (ethylene carbonate) content. Degradation rate in the peritoneal cavity was faster than that in subcutaneous tissue in guinea pigs.Membranes free from pores were obtained from poly (ethylene carbonate). Permeability of drugs through them depended on lipophilicity indicating role of solubility of the drugs in the membrane material for permeation.Release rate of tegafur from poly (ethylene carbonate) implants was faster than that from poly (propylene carbonate) implants. Blood level profiles were obtained after implantation of implants in rats.Microspheres containing local anesthetics were prepared by a solvent evaporation process and effects of drug content and polymer on release profiles were examined in vitro. Duration of local anesthesia after administration of dibucaine microspheres in guinea pigs was demonstrated.

著者

田村 類 高橋 弘樹 生塩 孝則

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.56, no.1, pp.22-33, 1998-01-01 (Released:2009-11-16)

参考文献数

16

被引用文献数

1 3

---

We have discovered the first case of accomplishment of an enantiomeric resolution by simple recrystallization of a series of racemic compounds [(±) forms] composed of a regular packing of (+) and (-) molecules in a crystal, although in principle this sort of enantiomeric resolution has been considered to be infeasible for more than a century since the discovery of chiral crystals by Pasteur and preferential crystallization of conglomerates by Gernetz which are a mixture of homochiral (+) and (-) crystals. We have designated this new enantiomeric resolution phenomenon as “Preferential Enrichment”. Here we report a distinct evidence that polymorphism between a racemic compound and a mixed crystal (solid solution), which consists of alternating alignment of the two homochiral dimers in a crystal, is responsible for the “Preferential Enrichment”, and we propose a mechanism of the phenomenon of the reversal of chirality in the deposited crystals, that is the essence of the “Preferential Enrichment”, on the basis of the polymorphic transformation during crystallization.