著者

横川 文明 塩入 孝之

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.7, pp.634-641, 2000-07-01

被引用文献数

4

---

Antillatoxin is an ichthyotoxic cyclic lipopeptide isolated by Gerwick and co-workers from the marine cyanobacterium <I>Lyngbya majuscula</I> collected in Curacao. Although we have finished the stereoselective total synthesis of antillatoxin having the proposed structure with (4<I>S</I>, 5<I>R</I>) -configuration, we have found that the synthetic sample was not identical with the natural one and the proposed structure should be revised. Further our synthetic efforts have culminated in the first total synthesis of antillatoxin in its natural form, proving that the natural one has (4<I>R</I>, 5<I>R</I>) -configuration. In this account, our total synthesis and synthetic studies by other groups will be discussed.

著者

右田 俊彦

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.27, no.7, pp.609-621, 1969

被引用文献数

1

---

1961年本誌に同じような標題のもとに、ラジカル反応のうち比較的収率のよい反応をあつめ, その後それらの反応に対する機構論的観察をとりまとめた。また古くから知られた反応までも含めて, 現在まで行なわれた実例がSosnovskyによって集録されている。<BR>ラジカル反応の合成化学的開発という意義をもつ研究はいまもなお盛んに行なわれているが, ここではその後見出された種々の反応を紹介すると共に, ラジカル反応を合成化学に利用するときの考え方に論点を向けてゆきたいと考えている<BR>多くのラジカル反応の教科書にみられるように, ラジカルの行なう反応を素反応別にわけると次のようになる。<BR>1.ラジカル1個の行なう反応<BR>R・→R'・+M (ラジカルの分解) <BR>R・→R'・ (ラジカルの転位) <BR>2.ラジカル間の反応<BR>R・+R・→R-R (会合反応) <BR>R・+R・→RH+R (-H) (不均化反応) <BR>3.ラジカルの酸化・還元<BR>R・+<I>e</I>→R : 〓<BR>R・-<I>e</I>→R⊕<BR>4.不飽和分子への付加<BR>R・+>C=C<→R-C-C・<BR>R・+O<SUB>2</SUB>→ROO・<BR>5.飽和分子との置換反応<BR>R・+X-C-→R-X+・C- (x-ひきぬき反応) <BR>R・+RLS-S-R, →R-S-R'+R'S・ (メタセシス) <BR>合成化学的に用いるという観点からこれらの反応を眺めてみよう。<BR>1.の反応はラジカルは安定分子を放出しつつ他のラジカルに変化し, あるいはより安定なラジカルに転位することがあることを示すもので, 中間に生ずるラジカルについてこの反応の可能性を考える必要がある。そして分解もしくは転位がきわめて収率よくおこるときは, それを利用して合成化学的に用いることもできよう。<BR>ラジカルに対してきわめて活性な芳香族化合物は過酸化ベンゾイルによってベンゾキシ化することができるが, 一般の芳香族化合物はフェニル化をうける。前者は過酸化物の分解によって生ずるベンゾキシラジカルの反応を, 後者はベンゾキシラジカルの分解で生じたフェニルラジカルの反応を利用した芳香核置換反応である。<BR>(C<SUB>6</SUB>H<SUB>5</SUB>COO) <SUB>2</SUB>→2C<SUB>6</SUB>H<SUB>5</SUB>COO・ArH→ArOOCCC<SUB>6</SUB>H<SUB>5</SUB><BR>C<SUB>6</SUB>H<SUB>5</SUB>COO・-CO<SUB>2</SUB>→C<SUB>6</SUB>H<SUB>5</SUB>・ArH→ARC<SUB>6</SUB>H<SUB>5</SUB><BR>3, 3-ジクロルプロペンに臭化水素をラジカル的に付加させるとき生成物は1, 2-ジクロル-3-プロムフロパンである。これは臭素原子がオレフィンに付加して生ずるラジカルに次の転位が行なわれたものである。<BR>Cl<SUB>2</SUB>CHCH=CH<SUB>2</SUB> →Br・→Cl<SUB>2</SUB>CHCHCH<SUB>2</SUB>Br→o <BR>ClCHCHCLCH<SUB>2</SUB>Br→HBrClCH<SUB>2</SUB>CHCLCH<SUB>2</SUB>Br<BR>しかし, ラジカルの分解または転位が重要な段階となる合成反応は少ないといってよい。<BR>2.の反応はラジカル2個が反応して安定分子を形成する反応である。このうち同種のラジカルが会合する反応は, 対称的な構造をもつ化合物の合成に用いられることがある。そのいくつかの例は先に上げた総説の中に集録したのでそれを参照していただきたい。<BR>不安定な多くのラジカルは溶液中では直ちに溶媒分子と反応するので, 会合が収率よくおこることを期待するためには生じたラジカルが多少とも安定でなくてはならない。クメン中過酸化物を分解させて1, 2-ジメチル-1, 2-ジフェニルブタンをつくる方法などがその典型的な例である。<BR>Ph-CH (CH<SUB>3</SUB>) <SUB>2</SUB> R・→Ph-C-CH<SUB>3</SUB>-CH<SUB>3</SUB>→Ph-Me-C-Me-Me-C-Me-Ph<BR>したがってその適用範囲もそう広いものではない。ラジカルを電解法によって発生させるときは, ラジカルの濃度が電極の近くに高くなるので, このような会合反応が期待できることがある。Kolbeの電解による炭化水素の合成はその例である。<BR>2CH<SUB>3</SUB>COO--<I>e</I>→2CH<SUB>3</SUB>COO・→-CO<SUB>2</SUB>2CH<SUB>3</SUB>・→C<SUB>2</SUB>H<SUB>6</SUB><BR>反応3.は炭素ラジカルを金属イオン等によって酸化あるいは還元してカルボニウムイオン, カルバニオンとする反応である。ラジカルは水とは反応しないが, カルボニウムイオンなどは水と容易に反応して相等するアルコールをうることができる。この種の研究は最近主としてKochiによって手広く行なわれている。なお今後の開発が期待される分野である。<BR>反応4, 5はラジカルの安定分子との反応である。不安定なラジカルは溶液中に発生すると, 直ちに溶液中の安定分子と反応4, 5の形式にしたがって反応する。したがって, 今日までに知られた合成に用いうる適用範囲の広い反応は, 反応4.あるいは5.の組み合せからなる連鎖反応であることは当然のことである。ここでも主してこの種の反応をとりあつかうことにする。

著者

荒井 緑 篠原 俊夫 荒井 孝義 笹井 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.1, pp.59-69, 2004-01-01

被引用文献数

5

---

The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis (isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate <I>via</I> double intramolecular nitrile oxide cycloaddition as a key step. The complex of (<I>M, S, S</I>) -R-SPRIX and Pd (OCOCF<SUB>3</SUB>)<SUB>2</SUB> promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization <I>via</I> oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIXs promote neither the Wacker-type reaction nor the tandem reaction.

著者

佐藤 則夫

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.49, no.6, pp.594-595, 1991-06-01 (Released:2009-11-16)

参考文献数

2

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ヘキサメチルジシラザンは有機ケイ素化合物の中でも良く知られた化合物であり, 分子内にケイ素-窒素結合をもつ化合物の代表である。良好なシリル化剤として有機合成反応でしばしば用いられる。他の有機ケイ素化合物と同じく天然には存在せず, 全て合成により製造されている。

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

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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

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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.