著者

小林 義郎 熊懐 稜丸 榛沢 雄二

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.37, no.3, pp.183-196, 1979-03-01 (Released:2009-11-13)

参考文献数

50

被引用文献数

2 2

---

Trifluoromethyl group shows a stabilizing effect on the compounds which would be unstable if they had no trifluoromethyl group. This review is concerned with two faces of the chemistry of trifluoromethylated valence bond isomers of aromatic compounds : Diels-Alder and 1, 3-dipolar reactions planned for the conversion of hexakis (trifluoromethyl) benzvalene to the corresponding tetrahedrane and the synthesis of new valence bond isomers of heteroaromatic compounds. In the former, the tetrahedrane itself could not yet be isolated, but the formation of tetrakis (trifluoromethyl) cyclobutadiene and new valence isomers of oxepin was confirmed. In the latter, Dewar thiopene, Dewar pyrrole, Dewar pyridine, and diphosphabenzvalene with trifluoromethyl groups were synthesized and their reactions were discussed. The effect of trifluoromethyl group is not limited to the strained compound. Thus, tetrakis (trifluoromethyl) -1, 4-diphosphabenzene, the first example of diphosphabenzenes, was synthesized.

著者

琴寄 崇

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.37, no.6, pp.486-493, 1979-06-01 (Released:2010-01-22)

参考文献数

5

---

Some case histories in chemical process occurred due to unexpected reaction in the past twelve years in Japan were collected, classified and discussed. As the result, chemical accidents of this type were found to occur mainly in reaction process, in distillation process, in drying or storage process (in which the causes are mostly similar to spontaneous ignition phenomena) and in pipe lines.Causes of accidents in the reaction process can be classified into two large groups, in which one is due to the fault of temperature control and the other is concerned with the miss in composition control of the reaction system. The typical examples of the fault of temperature control are as follows breakdown of electric power supply, breakdown of temperature control instruments, infelicity of the positon of the temperature sensor, etc. And that of the miss in composition control are : breakdown of measuring instruments, mistake in feeding control of reactants or catalyst, fault associated with agitating operation, trouble in enlarging the scale of operation, etc.On distillation process, it is stated that special caution should be given to impurities such as catalyst or its derivative for recovery that may be carried forward with the crude distillate to the distillation process.In addition, some comments are given on how to investigate the course of accident.

著者

目 武雄

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.32, no.10, pp.763-776, 1974 (Released:2009-11-13)

参考文献数

39

被引用文献数

3 3

著者

橋本 貞夫 鈴江 崇志

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.6, pp.528-537, 1980-06-01 (Released:2009-11-13)

参考文献数

33

被引用文献数

1 2

---

1- (Tetrahydro-2-furanyl) -5-fluorouracil (Futraful®, FT-207) was synthesized by S.A. Hiller, et al. in 1967. In this 5-fluorouracil (5-FU) derivative, a tetrahydrofuran group replace the sugar on the nucleoside.FT-207 is an antimetabolite, anti-tumor agent, and is well absorbed from the intenstine. It is gradually metabolized to substances such as 5-FU, 5-fluorouridine (FUR) and 5-Fluorouridine monophosphate (FUMP), which exhibit anti-tumor activity. These active substances are maintained in the blood and tissues for a long time, and thus FT-207 shows significant anti-tumor activity.FT-207 has less effect than other anti-tumor agents on antibody production, the blood picture and the functions of the liver, spleen and kidney. Thus since it has only side effects, it can be used for a long-term therapeutic treatment.It is effective when given intravenously, orally or intrarectally and has been employed clinically to induce tumor regression and to maintain regression and inhibit metastases.

著者

ウイルシヤー イーアール

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.12, no.4, pp.144-150, 1954

著者

服部 弘

出版者

公益社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.76, no.12, pp.1358-1359, 2018-12-01 (Released:2018-12-12)

参考文献数

13

---

Biocatalytic reactions are recently attracting attention as they offer various advantage over chemocatalysts and classical organic synthesis. Aided by the development of engineering techniques, such as site-directed mutagenesis and directed evolution, biocatalysts are modified to realize sustainable organic synthesis of API and natural products. In this mini review, recent applications of biocatalytic reactions in total synthesis of natural products are presented.

著者

中田 忠

出版者

公益社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.59, no.12, pp.1156, 2001-12-01 (Released:2009-11-13)

著者

吉岡 明 山田 俊郎

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.48, no.1, pp.56-64, 1990-01-01 (Released:2009-11-13)

参考文献数

50

被引用文献数

5 6

---

An economical synthetic process of methyl jasmonate has been established.Total yield of this process is higher than 60 % for all five steps from cheaply available adipic acid. 2-Pentyny1-2-cyclopentenone, the key intermediate in this route, is synthesized by applying the improved palladiumcatalyzed enone formation from allyl β-keto carboxylate as a key reaction. The pentynyl moiety is introduced by the use of pentynyl chloride which is prepared in two steps from 2-butyne, our original source, cheaply.

著者

橋山 富樹

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.5, pp.394-400, 1999-05-01 (Released:2009-11-16)

参考文献数

14

被引用文献数

3 3

---

An efficient method for preparation of diltiazem hydrochloride, a representive calcium antagonist widely used for the treatment of ischemic heart disease all over the world, is described. In the reaction of 2-nitrothiophenol (1) with trans-3-phenylglycidic esters (2) carrying various substituents on the benzene ring, both reactivity and stereoselectivity of the oxirane ring-opening of the glycidates were markedly influenced by the electronic nature of the substituents. As a result of our investigation on the catalytic effect of various Lewis acids in the reaction of 2a with 1, tin compounds were found to be effective catalysts for the cis-opening and readily produced the threo-nitro ester (3a), a key intermediate for the synthesis of diltiazem.Isolation of the crystalline complex from the reaction of 1 with SnCl4 and its efficient catalytic activity similar to that of SnCl4 suggest that the transition state involves co-cordination of tin derivatives both with 1 and the epoxy oxygen of 2a to result in highly specific cis-opening.

著者

松本 純一 由田 薫

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.53, no.9, pp.822-827, 1995-09-01 (Released:2009-11-16)

参考文献数

12

被引用文献数

1 3

著者

小松 弘典 及川 利洋 石橋 大樹

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.6, pp.594-603, 2005-06-01 (Released:2009-11-13)

参考文献数

30

被引用文献数

2 4

---

The demand for 2'-deoxynucleosides is increasing rapidly in the fields of gene therapy, biological research, and medical diagnosis. Development of an efficient synthetic method has been expected over the past few decades. We developed a novel synthetic method applicable to industrial manufacture of all four natural 2'-deoxynucleosides. Chemically synthesized 2-deoxyribose 1-α-phosphate (dRP) was enzymatically converted to thymidine (T), 2'-deoxycytidine (dC), 2'-deoxyadenosine (dA), and 2'-deoxyguanosine (dG) in the presence of nucleoside phosphorylase. This chemo-enzymatic method consists of three distinctive technologies : (i) stereoselective synthesis of dRP by crystallization-induced asymmetric transformation; (ii) an efficient method to expedite enzymatic conversions by adding Mg (OH)2; (iii) development of a new enzyme for the enzymatic synthesis of dC.

著者

山野 光久

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.9, pp.907-913, 2007-09-01 (Released:2010-10-20)

参考文献数

25

被引用文献数

3

著者

加々良 耕二 五島 俊介 市原 正治

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.5, pp.415-421, 1999-05-01 (Released:2009-11-16)

参考文献数

9

被引用文献数

6 7

---

Vamicamide is a new anticholinergic agent useful for the treatment of urinary incontinence. Vamicamide is synthesized from benzonitrile in 6 steps which include reductive amination and separation of diastereomers as key steps. In this paper, the process development of Vamicamide is described not only from the point of organic synthesis but also from the industrialization standpoints such as scale-up, economy, safety and environmental control.

著者

伊藤 孝浩 間瀬 俊明

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.65, no.6, pp.563-574, 2007-06-01 (Released:2010-10-20)

参考文献数

53

被引用文献数

1 1

---

Obesity poses a major risk for metabolic diseases like diabetes, hyperlipemia, cardiovascular disease and so on. Endogenous neuropeptide Y (NPY) is mediated by NPY receptors to cause the function which is involved in regulating feeding behavior. Recently, our basic research efforts identified highly potent and orally active NPY receptor antagonists. In this review article, we describe practical syntheses of three drug candidates from process chemistry perspective.

著者

古谷 敏行

出版者

公益社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.59, no.5, pp.510-511, 2001-05-01 (Released:2009-11-13)

参考文献数

5

被引用文献数

1 2

---

筆者の所属する部門では原薬製造プロセスを研究しており, 新薬の効率的製法開発と既製品の工程改良による製造コスト削減を目指している。このなかで, 主に酵素反応と有機合成反応とを組み合わせた, いわゆるハイブリッドプロセスを基盤として研究を行っている。このような分野に従事してきたなかで, 最も強く関わってきたのがジルチアゼムの製法開発である。ジルチアゼムは, 田辺製薬 (株) で開発された冠血管拡張剤であり, 100ヵ国以上で販売され今なお世界的に高い評価を受けている。ここではジルチアゼムの製法開発例を通じて, 企業の研究者としてプロセス研究の進め方・考え方を披露したい。ジルチアゼムは1, 5-ベンゾチアゼピン骨格を有し, 2つの不斉炭素をもつため4種類の構造異性体が存在する。このうち主作用を有するものは (2S, 3S) 体であり, 当初から光学活性体として開発された。スキーム1に当社で開発した主な製造ルートを示す。当初の製造にはジアステレオマー光学分割法によって (2S, 3S) -3を得る方法が採用された。しかし, その後この方法は工程数が長いことと, 分割により大量の廃棄物が副生することから, さらに効率的な製法開発が要望された。一般に光学活性体の製造において, 後工程でラセミ化が起こらない限り, なるべく出発原料に近い段階でキラリティーを構築するのが, 生産効率・経済性・廃棄物処理の面で有利である。この考えに基づいて, transラセミ体として最初に不斉中心が現れる (2RS, 3SR) -グリシッド酸エステル2での光学分割に注目した。しかし, (2RS, 3SR) -2は, 酸・塩基の官能基をもたず, さらにベンゼン環に隣接して反応性に富むオキシラン環を有するため, ジァステレオマー誘導法などの光学分割は困難であった。

著者

平井 功一 丸山 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.57, no.5, pp.382-386, 1999-05-01 (Released:2009-11-16)

参考文献数

9

被引用文献数

1 1

---

Several problems encountered during the kg scale production of such an unstable carbapenem antibiotic “Panipenem” (CS-533) was overcome by scrutinizing the reaction conditions and the factors influencing the reactions. Each item was reviewed from the nostalgic standpoint of a basic organic chemist, and the hard work of isolation technology is described at the same time.

著者

高松 聡 丸山 徳見 井澤 邦輔

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.9, pp.864-878, 2005-09-01 (Released:2009-11-13)

参考文献数

39

被引用文献数

2 3

---

Lodenosine, [9- (2, 3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl) adenine, FddA, 1] is an acid-stable purine nucleoside analog with activity against human immunodeficiency virus (HIV). There are two possible approaches to 1 - the glycosylation of a nucleoside base with a fluorinated sugar or direct nucleoside fluorination. However, both methods have drawbacks in terms of the number of steps, the use of toxic agents and low overall yields. In this review article, we describe two industrial synthetic approaches to 1 via 6-chloropurine riboside and 6-chloropurine 3'-deoxyribo-side, the latter being derived from inosine, a readily available starting material produced by fer-mentation. Several deoxygenation and fluorination methods are compared considering reaction yields, cost, safety and environmental concerns.

著者

飯沼 勝春 村井 安

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.5, pp.368-373, 1999-05-01 (Released:2009-11-16)

参考文献数

7

被引用文献数

2 2

---

Arbekacin, aminoglycoside antibiotic, was synthesized in 1973 by Kondo et al starting from Dibekacin by the acylation of 1-amino group with (S) -4-amino-2-hydroxybutyric acid (AHB), and approved as a chemotherapeutic agent in 1990 limiting to MRSA infection. In the development of industrial large scale synthesis, the main theme was selective protection of four amino groups except 1-amino group. We focused our effort to set up large scale synthetic method by taking advantage of zinc-chelation reaction. By the optimization of reaction conditions and minimization of isolation procedures, final production method was completed. We herein report the development course of high yield and low cost production method by the selective protection of amino group.

著者

西脇 正憲

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.61, no.5, pp.464-471, 2003-05-01 (Released:2009-11-13)

参考文献数

12

被引用文献数

3 4

---

Recently, green chemistry (GC) plays an important role for manufacturing active pharmaceutical ingredients (APIs) at pharmaceutical companies. For example, large amount of aluminum waste was originally involved and dichloromethane used as a solvent in the process of a new anticholinergic agent, Vamicamide (FK 176), useful for the treatment of urinary incontinence. Non-selective and tedious procedures for alkylation of quinazoline nucleous were used on a laboratory scale in the process of a novel aldose reductase inhibitor, Zenarestat (FK 366) developed for the remedy of diabetic complications. These problems must be excluded before realizing a truly efficient process on a large scale. New process involved much less amount of waste in the case of Vamicamide, and utilized regioselective alkylation reaction for Zenarestat. As a result, E-factor and reaction mass efficiency (RME) were dramatically improved. Herein, we report our efforts leading to an efficient, practical and environmentally friendly process amenable to a large scale synthesis.

著者

橋本 俊一 本田 雄 柳谷 由己 中島 誠 池上 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.53, no.7, pp.620-632, 1995-07-01 (Released:2009-11-16)

参考文献数

38

被引用文献数

4 6

---

The rational design and development of stereocontrolled glycosidation reactions has been the subject of intensive investigations. Our interest in this context has been centered on the design of the leaving groups of glycosyl donors coupled with their activation without resorting to precious, explosive, or toxic heavy-metal salts as promoters. In an effort to capitalize on the phosphorus-containing leaving groups, we have recently devised new glycosyl donors incorporating diphenyl phosphate, diphenylphosphinimidate, N, N, N', N'-tetramethylphosphoroamidate, phosphorodiamidimidothioate, or diethyl phosphite as leaving groups, the glycosidations of which constitute mild and efficient methods for the highly stereocontrolled construction of 1, 2-trans-β-and 1, 2-cis-α-glycosidic linkages. In this paper, several notable features of the present glyosidation methods coupled with the mechanistic aspects are described.