文献一覧: 藤本勝彦 (著者)

2 0 0 0 OA Antitumor Agents. II : Regio- and Stereospecific Syntheses of 1-β-Alkyl-1-desoxypodophyllotoxin Derivatives and Biological Activity

著者: 寺田忠史藤本勝彦野村誠山下純一 / 小武内尚武田節夫南慶典吉田健一郎山口秀夫山田雄次 Yuji YAMADA
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.41, no.5, pp.907-912, 1993-05-15 (Released:2008-03-31)
参考文献数: 58
被引用文献数: 6 10

1-β-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined.The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-β-allylated compounds (2a-c). The regiochemistry and the β-stereochemistry of the 1-allyl group were confirmed by comparison of the 13C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-β-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b.None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-β-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-β-(2, 3-Dihydroxypropyl) compounds (5 and 8) and 1-β-(2, 3-diacetoxypropyl) compounds (6 and 7)showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.

2022-02-07 17:31:23
2 + 1 Twitter

2 0 0 0 OA A New Synthetic Route to Optically Active α, β- and β', γ'-Unsaturated Alcohols, and Its Application to the Synthesis of a Fungitoxic C-18 Hydroxy Unsaturated Fatty Acid

著者: 樫原宏末宗洋藤本勝彦酒井浄
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.37, no.10, pp.2610-2614, 1989-10-25 (Released:2008-03-31)
参考文献数: 17
被引用文献数: 7 9

A new synthetic route to optically active α, β-, β', γ'-unsaturated alcohols was established. The chiral enones (6 and 8), prepared from dimethyl malate via chiral phosphonates (4 and 5), were diastereoselectively reduced with Zn(BH4)2 to afford the 1, 3-syn derivatives (9 and 11). As an application of this 1, 3-asymmetric induction, the fungitoxic C-18 hydroxy unsaturated fatty acid isolated from stromata of Epichloe typhina was synthesized.

2022-02-04 22:11:19
2 + 3 Twitter

2 0 0 0 Antitumor Agents. II. Regio- and Stereospecific Syntheses of 1-.BETA.-Alkyl-1-desoxypodophyllotoxin Derivatives and Biological Activity.

著者: 寺田忠史山田雄次野村誠藤本勝彦野村誠山下純一 / 小武内尚武田節夫南慶典吉田健一郎山口秀夫
出版者: 公益社団法人日本薬学会
雑誌: CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
巻号頁・発行日: vol.41, no.5, pp.907-912, 1993
被引用文献数: 10

1-β-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined.The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-β-allylated compounds (2a-c). The regiochemistry and the β-stereochemistry of the 1-allyl group were confirmed by comparison of the <SUP>13</SUP>C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-β-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b.None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-β-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-β-(2, 3-Dihydroxypropyl) compounds (5 and 8) and 1-β-(2, 3-diacetoxypropyl) compounds (6 and 7)showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.

2016-04-30 21:21:56
2 + 0 Twitter

2 0 0 0 Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents.

著者: 寺田忠史藤本勝彦野村誠山下純一小武内尚武田節夫 / 山田雄次山口秀夫山口秀夫
出版者: 公益社団法人日本薬学会
雑誌: CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
巻号頁・発行日: vol.40, no.10, pp.2720-2727, 1992
被引用文献数: 27

Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210).An intact 6, 7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity.The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following : 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

2016-04-30 21:21:07
2 + 0 Twitter

1 0 0 0 OA Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents

著者: 寺田忠史藤本勝彦野村誠山下純一小武内尚武田節夫 / 山田雄次山口秀夫 Hideo YAMAGUCHI
出版者: The Pharmaceutical Society of Japan
雑誌: Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日: vol.40, no.10, pp.2720-2727, 1992-10-25 (Released:2008-03-31)
参考文献数: 34
被引用文献数: 21 27

2018-06-16 03:34:45
1 + 0 Twitter