著者

田中 博道 内田 祐子 篠崎 操 早川 弘之 松田 彰 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.2, pp.787-790, 1983-02-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

21 32

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6-Chloro-9-(2, 3-O-isopropylidene-β-D-ribofuranosyl) purine (1) was found to be a suitable substrate for the preparation of C-8 substituted purine nucleosides. Thus, upon lithiation of 1 with LDA and successive reaction with various types of electrophiles, the C-8 substituted products were obtained. The C-6 chlorine atoms in these products were readily replaced by an amino group, a mercapto group, or hydrogen, providing a facile preparation of 8-substituted adenosines, 6-thioinosines, or nebularines.

著者

早川 弘之 高井 富美 田中 博道 宮坂 貞 山口 健太郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.5, pp.1136-1139, 1990-05-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

18 23

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Displacement of a hydroxyl group in pyrimidine nucleosides having a vicinal diol system by a fluorine atom was investigated by using diethylaminosulfur trifluoride (DAST). Though participation of the base moiety often thwarts the desired introduction of a fluorine atom, it was found that appropriate modification of the base and/or sugar moieties allowed the desired fluorodehydroxylation to occur, giving 5'-, 3'-β-, and 2'-α-fluorinated uracilnucleosides in good yields.

著者

田中 博道 松田 彰 飯島 秀治 早川 弘之 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.6, pp.2164-2167, 1983-06-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

25 40

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A new class of 5, 6-disubstituted uridines, in which the C-6 position was occupied by phenylthio group or iodine, were synthesized via lithiation of the corresponding 5-substituted 2', 3'-O-isopropylidene-5'-O-methoxymethyluridines and subsequent electrophilic reactions. These newly-synthesized uridine derivatives exhibited antileukemic activities against mouse leukemia L5178Y cells in culture.

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

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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

早川 弘之 原 裕淳

出版者

公益社団法人日本オペレーションズ・リサーチ学会

雑誌

オペレーションズ・リサーチ : 経営の科学 (ISSN:00303674)

巻号頁・発行日

vol.47, no.8, pp.499-504, 2002-08-01