著者

高木 泰 土屋 務 三宅 俊昭 竹内 富雄 梅澤 純夫

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.2, pp.131-142, 1992-02-01 (Released:2009-11-16)

参考文献数

41

被引用文献数

3 4

---

Anthracycline antibiotics, represented by daunorubicin and doxorubicin, are important antitumor agents widely used in clinical treatment. Their use is, however, restricted by the cardiotoxic character and other undesirable side-effects. To overcome these drawbacks and expand the utility, many efforts have been made for the past two decades. Recently we have synthesized a compound with strong antitumor activity and weak toxicity, 7-O- (2, 6-dideoxy-2-fluoro-α-L-talopyranosyl) adriamycinone, in which the glycosidic bond is comparatively stable in acid-catalyzed hydrolysis by the presence of highly electronegative fluorine atom at C-2'. This article describes the recent studies on the synthesis of the 2'-fluoroanthracycline antibiotics and their 14, 3', and 4'-substituted derivatives together with structure-activity relationship. It was found that R-configuration at C-2' having the fluorine is requisite to exhibit strong antitumor activity; thus (2'S) -fluoro and 2', 2'-difluoro analogs were devoid of activity. Synthesis of 2'-methoxyl analogs is also described.

著者

西村 吉雄

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.55, no.2, pp.142-151, 1997-02-01 (Released:2009-11-16)

参考文献数

42

被引用文献数

1 1

---

Specific inhibitors of glycosidases are aiding in unraveling how oligosaccharides of glycoconjugates, as the functional domains for carbohydrate-protein interactions, regulate biological functions, and how they produce beneficial pharmaceutical effects in the prevention and treatment of a variety of diseases.This paper describes the progress of the synthesis of iminosugar glycosidase inhibitors, siastatin B analogues toward the rational drug design of D-glucuronic acid and L-iduronic acid-based inhibitors for tumor invasion, and of sialic acid-based inhibitors for the influenza virus sialidase, as well as indicating progress in the development of a new therapeutic and prophylactic treatment for tumor metastasis and influenza infection.

著者

近藤 信一 池田 大四郎

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.10, pp.902-911, 1982 (Released:2010-01-22)

参考文献数

79

被引用文献数

2 2

---

Several 1, 4-diaminocyclitol-containing aminoglycoside antibiotics have been discovered by four Japanese research groups during the past five years. Fortimicin A, C, D and KG3 produced by Micromonospora, sporaricin A and C by Saccharopolyspora, istamycin A, B, C and A2, 2″- N-form-imidoylistamycin A and B by Streptomyces, and dactimicin by Dactylosporangium inhibit strongly the growth of Grampositive and -negative bacteria including most aminoglycosides-resistant strains. These antibiotics are pseudodisaccharides consisting of a diaminosugar and a 1, 4-diaminocyclitol acylated with glycine at the 4-methylamino group. Fortimicin A and some derivatives of this group antibiotics have been evaluated their clinical usefulness. In this review, chemical studies and structure-activty relationships of the 1, 4-diaminocyclitol-aminoglycoside antibiotics are discussed.

著者

大和 隆志 杉山 亨 須賀 亮 大塚 雅巳 大野 雅二

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.48, no.3, pp.194-205, 1990-03-01 (Released:2009-11-13)

参考文献数

31

被引用文献数

1

---

Bleomycins (BLMs) are antitumor antibiotics of unusual glycopeptide structure. The potent activity of BLM is attributed to the oxygen activation and the DNA cleavage by the formation of iron-chelate of the peptide moiety. erythro-β-Hydroxy-L-histidine, a pivotal amino acid for the oxygen activation, is prepared enantioselectively by aldol reaction of (R) -3-bromoacetyl-4-isopropyl-1, 3-oxazolidin-2-one with 1-triphenylmethylimidazole-4-carbaldehyde. Model ligands for the metal binding site of BLM with 4-methoxypyridine (PYML-6) and 4-dimethylaminopyridine (PYML-8) show oxygen activation up to 97% and 125% of that of BLM, respectively. cis-β-Methylstyrene is oxidized either with Fe (III) -H2O2 or Fe (II) -O2 complex systems of BLM and PYML-6 to give the corresponding optically active epoxide. The DNA binding region of BLM is combined with PYML-6 to give the first man-designed BLM, PYML (6) -bleomycin, which shows nucleotide cleavage mode remarkably similar to that of BLM. On the other hand, PYML-6 moiety and distamycin are coupled to afford PYML (6) - (4R-APA) -distamycin which shows dramatically altered AT specific mode in the DNA scission.

著者

市川 英子 加藤 國基

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.4, pp.331-345, 2001-04-01 (Released:2010-01-22)

参考文献数

181

被引用文献数

6 7

---

In the search for effective, selective, and nontoxic antiviral and antitumour agents, a variety of strategies have been devised to design nucleoside analogs. These strategies have involved several formal modifications of the naturally occurring nucleosides, especially, alteration of the carbohydrate moiety. Since the naturally occurring purine nucleoside analog oxetanocin A and its derivatives have been found to be effective as anti-HIV-1 and anti-herpes virus agents in 1986, the syntheses of different types of sugar-modified nucleoside analogs have been reported. In this review we will give an overview of the sugar-modified nucleosides synthesized since the late 1990 according to their structural types along with the synthetic routes of some nucleosides.

著者

田中 博道 早川 弘之 宮坂 貞

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.49, no.12, pp.1142-1155, 1991-12-01 (Released:2009-11-16)

参考文献数

63

被引用文献数

2 6

---

Lithiation of nucleosides has been shown to be a highly general method for chemical modification of the base moiety. A wide range of substitutions can be accomplished simply by using different electrophiles in the reaction with the respective lithiated species.In the case of uridine, the protecting group of the sugar hydroxyl groups appeared to be an important determinant of the efficiency and regiochemical outcome of the lithiation. Regiospecific abstraction of H-6 in uracil moiety with LDA takes place only when 2'- and 3'-hydroxyl groups are simultaneously protected with an alkylidene group, e.g. isopropylidene group. Subsequent reaction with a variety of electrophiles furnishes 6-substituted derivatives, which are difficult to synthesize by any other methods.As an application of the C-6 lithiation with LDA, a series of 6-iodo and 6-phenylthio acyclouridines were synthesized. Among these derivatives, 1- [(2-hydroxyethoxy) methyl] -6-phenylthiothymine (HEPT) was found to be a new lead for anti-HIV agents. The activity of HEPT is highly specific to HIV-1 : other viruses, including HIV-2, are totally non-susceptible to HEPT. Further synthetic study improved the activity to a greater extent. In terms of excellent activity, low toxicity, and effectiveness against AZT-resistant HIV-1, these HEPT analogues constitute promising candidates for AIDS chemotherapy.

著者

熊本 浩樹 田中 博道

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.2, pp.145-154, 2002-02-01 (Released:2009-11-13)

参考文献数

25

被引用文献数

1 2

---

Described herein are three types of anionic migration of silyl and stannyl groups observed during the lithiation (hydrogen-lithium exchange) of nucleosides. In the first example of 9- [2, 3, 5-tris-O- (tert-butyldimethylsilyl) -β-D-ribofuranosyl]-6-chloropurine, the 8-trimethylsilyl or 8-tributylstannyl group introduced by lithiation underwent migration to the 2-position (migration within the base) through further lithiation of the less acidic H-2. The second example was observed by using 1- (2-deoxy-D-erythro-pent-1-enofuranosyl) uracil as a substrate, wherein the lithiationbased migration took place from the 6-position of the nucleobase to the 2'-position of the sugar (furanoid glycal). The last example came from the lithiation of the 5'-O-silylated or -stannylated anti-HIV agent d 4 T (2', 3'-didehydro-3'-deoxythymidine). As a result of highly unusual vinylic lithiation in the presence of allylic hydrogen, these 5'-O-protecting groups were transferred to the 3'-position of the unsaturated sugar (migration within the sugar). Since stannyl group can be transformed in various ways, the above three examples have opened up access to nucleoside derivatives that have been difficult to be synthesized by other methods.

著者

池原 森男 大塚 栄子

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.38, no.11, pp.1092-1099, 1980-11-01 (Released:2010-01-22)

参考文献数

48

被引用文献数

2 2

---

1 Discovery of 2-5 A2.1.5 Methoxytetrahydopyranyl protection2 Synthesis of 2-5 A2.1.6 Metal catalyzed synthesis2.1 Formation of 2'-5' internucletide linkages2.2 Formation of 5'-triphsosphate (Synthesis of A 2' p 5' A 2' p5' A) 2. 2. 1 5'-Phosphorylation2.1.1 Enzymatic synthesis2.2.2 5'-Triphosphorylation with DCC2.1.2 Chemical method using benzoyl protection2.2.3 Carbonylimidazolide method2. 1. 3 o-Nitobenzyl protection2.2. 4 Other methods2. 1. 4 Silyl protection3 Biological activity of 2-5 A

著者

小林 義郎 熊懐 稜丸 田口 武夫

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.38, no.11, pp.1119-1129, 1980-11-01 (Released:2010-01-22)

参考文献数

36

被引用文献数

3 4

---

First, characteristics of a carbon-fluorine bond from the biological point of view are summarized with some examples : mimic effect, protective fluorination, irreversible conjugation with enzyme, increased lipophilicity and so on are presented. Secondly, some approaches to biologically active compounds utilizing the above characteristics are shown by the examples of trifluoromethylated nucleoside derivatives and fluorinated vitamin D3 analogues.

著者

永田 亘 成定 昌幸

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.38, no.11, pp.1009-1024, 1980-11-01 (Released:2009-11-13)

参考文献数

90

被引用文献数

2 3

---

Progress in synthetic studies on 1-oxacephems is reviewed. Antibacterial activity of this new class of compounds is also discussed briefly. Earlier syntheses, rather lengthy but quite pioneering, provided us with valuable information of the interesting biological activity of 1-oxacephems. Several improved synthesis have appeared, enabling to prepare a variety of derivatives and examine their antibacterial activity. Thus, syntheses and antibacterial activity of some interesting 1-oxacephems and 7α-methoxy-1-oxacephems, such as, arylmalonamido-, α-acylureidophenylacetamido-, and α-aminothiazolyl-α-methoxyiminoacetamido derivatives with representative 3'-substituents are described. A compound 6059-S 98 discovered in Shionogi Research Laboratories, proved to have excellent antibacterial activity, spectrum, and other pharmacological properties and, therefore, is currently under clinical studies. An industrially feasible synthetic method for its nucleus 88 a as well as 7α-methoxy-1-oxacephem nuclei with a variety of substituents at the 3'-position in general was established after extensive studies.

著者

亀谷 哲治 井原 正隆

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.38, no.11, pp.1025-1036, 1980-11-01 (Released:2010-01-22)

参考文献数

38

被引用文献数

5 9

---

Thienamycin, an exceptionally potent, broad spectrum β-lactam antibiotic, possesses a novel 1-carbapen-2-em structure. Total syntheses and synthetic approaches of thienamycin and its related compounds, which have been published before early in June of 1980, are summarized according to the manner for the formation of carbapenem and carbapenam ring systems.

著者

松田 譲

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.2, pp.152-158, 1997-02-01 (Released:2009-11-16)

参考文献数

19

被引用文献数

2 1

著者

喜谷 喜徳

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.38, no.11, pp.1063-1076, 1980-11-01 (Released:2010-01-22)

参考文献数

31

被引用文献数

1 1

---

Since the discovery of the antitumor activity of cis-dichlorodiammineplatinum (II) (=DDP) by B. Rosenberg et al. in 1969, various diamino Pt complexes have been synthesized and their antitumor activities were tested, in order to prepare more potent Pt complexes, with least toxicity. cis-DDP was found very effective and it had been approved by the Food and Drug Administration, U.S.A. in December, 1978 as an antitumor agent for the treatmet of bladder cancer, ovarian cancer, testis cancer and, head and neck cancer. The problem is the kidney toxicity and severe nausea and vomiting, when DDP was administered to the patients. Ototoxicity is also another problem.Various Pt complexes were synthesized by replacing carrier ligands, and mono- and bi-dentate leaving groups. 1, 2- Cyclohexanediamine (= dach) is considered to be one of the useful carrier ligands. Dach has two geometrical isomers, cis and trans, and the latter is resolved into two optical isomers, d and l.Among the Pt complexes prepared in my laboratory, D-glucuronato and D-gluconato Pt (II) complexes of trans-1-dach are water-soluble and potential antitumor agents.2- (Aminomethyl) cyclohexylamine and stilbenediamine were synthesized. The former has two geometrical isomers, each of which has two optical isomers, while the latter has three isomers, meso, trans-d and trans-l. Preparation of their Pt (II) complexes and their antitumor activities are described.

著者

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.49, no.11, pp.1032-1042, 1991-11-01 (Released:2009-11-16)

参考文献数

16

被引用文献数

7 9

---

The first generation of 10 membered ring analogues (11-13) of the neocarzinostatin chromophore (1) could undergo the thiol or radical triggered Masamune-Bergman type cycloaromatization, but they were not able to show the antibiotic nor antitumor activities. New analogues (2729) of the second generation exhibited the remarkable DNA cleaving activities as well as the biological activities. The unprecedented guanine specific DNA cleavage by the simple chiral alcohol 28 is striking, while the complex of the possible intercalator 29 with the neocarzinostatin apoprotein (2) did not show an evident specificity.

著者

戸嶋 一敦 中田 雅也 松村 秀一

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.6, pp.503-513, 1996-06-01 (Released:2009-11-16)

参考文献数

23

被引用文献数

1 2

---

The molecular design and chemical synthesis of novel and artificial enediyne classes of DNA cleaving molecules 14, and their chemical and DNA cleaving profiles are described. The enediyne sulfides 1aI were synthesized via the coupling of the vinyl iodide 8 and the protected propargyl alcohol 9, and the intramolecular cyclization of the dibromide 17. 1b was found to cycloaromatize by 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) in 1, 4-cyclohexadiene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. 1aI cleaved DNA under weakly alkaline conditions, and 1e, 1k and 1l, all of which have a DNA intercalatable moiety, exhibited strong DNA cleaving activities with the identical high purine base (G>A) selectivity. The enediyne triols 2ac were prepared from xylitol (19) via the conversion of the keto-aldehyde 24 into the keto-enediyne 25 by an intramolecular aldol reaction. 2a was also cycloaromatized in a manner similar to that for the enediyne sulfide, and 2ac showed guanine-specific DNA cleavages under weakly alkaline conditions. The enynallene sulfones 3af were obtained by m-CPBA oxidation of the corresponding enediyne sulfides. 3c was cycloaromatized by DBU through both radical and polar pathways. 3af cleaved DNA at any DNA-base site under weakly alkaline conditions, and 3df possessing a hydrophilic moiety exhibited stronger DNA cleavages. The dienediynes 4ac were synthesized from 25. 4c possessing acetoxy groups at the propargylic positions was cycloaromatized by methyl thioglycolate through radical pathways, and cleaved DNA at any pH with guanine-base selectivity. Furthermore, the DNA cleaving activity of 4c significantly increased in the presence of methyl thioglycolate.

著者

菅原 徹

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.5, pp.465-475, 2002-05-01 (Released:2009-11-13)

参考文献数

54

被引用文献数

1 4

---

Historically chemical automation was started in the field of analytical chemistry and until around 1992 only a few instrument makers and laboratories had studied the automation of organic synthesis chemistry (1st stage). Along side the growth of combinatorial chemistry, considerable attention has since been paid to developing automated synthesis apparatus and the accompanying peripheral apparatus, especially for the efficient development of new drugs in pharmaceutical companies (2nd stage). Recently many kinds of special-purpose automated modules and units have been developed for solid and solution phase synthesis, especially for high throughput parallel synthesis, isolations and purifications.In this report, I will briefly look at the history of laboratory automation, offer some advice on how to carry it out and then describe some future prospects.

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.