- 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.
- 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.
- 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.
- 著者
- 山口 秀夫
- 出版者
- 一般財団法人 日本英文学会
- 雑誌
- 英文学研究 (ISSN:00393649)
- 巻号頁・発行日
- vol.53, no.1-2, pp.226-232, 1976-12-01 (Released:2017-04-10)
- 著者
- 田之口 真理子 加島 竜彦 雑賀 英之 井上 大志 有本 正生 山口 秀夫
- 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.1, pp.68-72, 1989-01-25 (Released:2008-03-31)
- 参考文献数
- 31
- 被引用文献数
- 11 16
Two new lignans, hernolactone (1) and fernandin (2), isolated from the seeds of Hernandia ovigera L. were synthesized in recemic forms. Firstly, (±)-1 was obtained by utilizing the conjugate addition reaction of 4 with butenolide followed by alkylation with trimethoxybenzyl bromide and subsequent removal of the protecting groups. Synthesis of 2 was pursued using the corresponding 4-phenyl-1, 2-dihydronaphthalene lactone(18). The cleavage of the lactone moiety of 18 afforded an unsaturated hydroxy acid (22). Subsequent hydrogenation of 22 followed by acidification with concetrated hydrochloric acid gave isopicrobernanadin (21), leaving the 2, 3-trans, 3, 4-cis hydroxy acid (23), which was lactonized by means of N, N-dicyclohexylcarbodiimide to afford (±)-2.
- 著者
- 田之口 真理子 細野 江津子 北岡 真由子 有本 正生 山口 秀夫
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.39, no.7, pp.1873-1876, 1991-07-25 (Released:2008-03-31)
- 参考文献数
- 10
- 被引用文献数
- 8 11
Two kinds of lignans were isolated from the seeds of Hernandia ovigera L. in addition to the nine lignans previously reported. One was confirmed as (-)-dimethylmatairesinol (11) and the other was identified as 5'-methoxypodorhizol (14) by comparison with the anthentic sample. An attempt at the cyclization of 14 afforded two compounds which were determined to be isohernandin (15) and an isomer of 15, 2-hydroxymethy 1-5, 6-methylenedioxy-7-methoxy-4-(3', 4', 5'-trimethoxyphenyl)-1, 2, 3, 4-tetrahydronaphthoic acid lactone (16).
- 著者
- 山口 秀夫 有本 正生 中島 淳二 田之口 眞理子 深田 能成
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.34, no.5, pp.2056-2060, 1986-05-25 (Released:2008-03-31)
- 参考文献数
- 16
- 被引用文献数
- 10 11
Epipodophyllotoxin (EPT) and podophyllotoxin (PT) were prepared from desoxypodophyllotoxin (DPT), obtained from the seeds of Hernandia ovigera L. (Hernandiaceae) EPT was obtaind together with dehydrodesoxypodophyllotoxin (I) by a radical bromination of DPT with N-bromosuccinimide (NBS) followed by hydrolysis of the resultant 1-bromo-DPT, which was confirmed to be a mixture of 1α- and 1β-bromo compounds (7 : 3). EPT was oxidized with pyridinium chlorochromate to give podophyllotoxone (IV). The stereoselective reduction of IV to afford PT was examined with a variety of reagents, and borane-tert-butylamine complex was found to be effective.
- 著者
- 山口 秀夫 中島 淳二 有本 正生 田之口 真理子 石田 寿昌 井上 正敏
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.32, no.5, pp.1754-1760, 1984-05-25 (Released:2008-03-31)
- 参考文献数
- 18
- 被引用文献数
- 2 5
Two kinds of 4-aryltetralin type lignans, β-peltatin-A methyl ether (I-A) and β-peltatin-B methyl ether (I-B), were synthesized from desoxypodophyllotoxin (DPT), which is available in large quantities from the seeds of Hernandia ovigera L. (Hernandiaceae). The syntheses were achieved via demethylene-DPT (IV), 8-bromo-demethylene-DPT (V) and 8-bromo-DPT (VI). Methylenation of V was carried out successfully by using cesium fluoride and methylene iodide in DMF. Compound I-B was readily obtained by the reaction of VI with cuprous iodide and sodium methoxide in the presence of pyridine. Synthesis of I-A was only achieved by the reaction of lithiated VI with nitrobenzene at-100°C in the presence of tetramethylethylene diamine, and I-A was obtained in low yield, together with I-B.
1 0 0 0 OA Studies on the Constituents of the Seeds of Hernandia ovigera L. III. Structures of Two New Lignans
- 著者
- 山口 秀夫 有本 正生 田之口 眞理子 石田 寿昌 井上 正敏
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.30, no.9, pp.3212-3218, 1982-09-25 (Released:2008-03-31)
- 参考文献数
- 22
- 被引用文献数
- 12 21
Two kinds of lignans were isolated from the seeds of Hernandia ovigera L. (Hernandiaceae) besides the previously reported desoxypodophyllotoxin (DPT), desoxypicropodophyllin, bursehernin and podorhizol, and the structures of the lignans were clarified. One, C23H24O8, named hernandin, was identified as 5-methoxy-desoxypodophyllotoxin (I) by both chemical and X-ray crystallographic methods. The other, C22H18O7, was obtained by purification of a previously isolated impure substance, mp 270-275°C. This compound was identified as 1, 2, 3, 4-dehydrodesoxypodophyllotoxin (II). This is the first report of the natural occurrence of II in plants.
- 著者
- 山口 秀夫 有本 正生 田之口 真理子 沼田 敦
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.101, no.5, pp.485-488, 1981-05-25 (Released:2008-05-30)
- 参考文献数
- 12
- 被引用文献数
- 5 7
Two kinds of reactions were carried out on the components of the seeds of Hernandia ovigera L. The reaction of lead tetraacetate on desoxypodophyllotoxin (I) and its analogous compounds caused the cleavage of methylenedioxyl group, affording the corresponding diphenols. In the case of 3, 4-methylenedioxypropylbenzene (XII), an intermediate acetoxyl compound (XIII) was isolated. The reactions of 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) on I and its analogous compounds afforded smoothly aromatized compounds. By the same reaction on bursehernin (III), cyclization and aromatization occurred simultaneously affording chinensin (XVIII) which was confirmed by direct comparison with authentic speciemen. The results of the cleavage reaction on I and XII by use of borontrichloride were also described.
1 0 0 0 OA ハスノハギリ(Hernandia ovigera L.)の種子成分研究
- 著者
- 山口 秀夫 有本 正生 山本 起巳子 沼田 敦
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.6, pp.674-677, 1979-06-25 (Released:2008-05-30)
- 参考文献数
- 15
- 被引用文献数
- 12 14
Four kinds of lignans were isolated from the seeds of Hernandia ovigera L. collected in Okinawa besides the previously reported desoxypodophyllotoxin (I). Oily substance II, named bursehernin, C21H22O6, was confirmed to be lignan-2 isolated from Bursera schlechtendalii. III, mp 171-173°, and IV, mp 125-126°, were determined as desoxypicropodophyllin and podorhizol obtained from Podophyllum emodi WALL. respectively. V, mp 270-275°, could not be clarified due to its small amount.
- 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
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.
- 著者
- 山口 秀夫 有本 正生 中島 淳二 田之口 眞理子 深田 能成
- 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.34, no.5, pp.2056-2060, 1986-05-25
Epipodophyllotoxin (EPT) and podophyllotoxin (PT) were prepared from desoxypodophyllotoxin (DPT), obtained from the seeds of Hernandia ovigera L. (Hernandiaceae) EPT was obtaind together with dehydrodesoxypodophyllotoxin (I) by a radical bromination of DPT with N-bromosuccinimide (NBS) followed by hydrolysis of the resultant 1-bromo-DPT, which was confirmed to be a mixture of 1α- and 1β-bromo compounds (7 : 3). EPT was oxidized with pyridinium chlorochromate to give podophyllotoxone (IV). The stereoselective reduction of IV to afford PT was examined with a variety of reagents, and borane-tert-butylamine complex was found to be effective.
- 著者
- 落合 正仁 藤田 榮一 有本 正生 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.33, no.3, pp.989-997, 1985-03-25
Oxidative cyclization of hydroxy allylsilanes utilizing the combination of a hypervalent organoiodine compound and a Lewis acid was studied. The allylsilanes 4,prepared from the γ-lactones 1 via conversion to the bis (trimethylsilylmethyl) carbinols 3,on treatment with iodosyl-benzene in the presence of boron trifluoride-etherate in an ethereal solution, afforded the 6-membered β-methylene cyclic ethers 13a and 13b in good yields. Similar treatment of the allylsilanes 8a and 8b gave the 5-membered cyclic ethers 13a and 13b. On the other hand, oxidative cyclization of the carboxylic acid 12 gave a poor yield of the lactone 21 and the major product was found to be the rearranged γ-keto acid 22. Regioselectivity in the iodine (III)-mediated cyclization of 8a is discussed.
- 著者
- 山口 秀夫 有本 正生 田之口 真理子 沼田 敦
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 藥學雜誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.101, no.5, pp.485-488, 1981
- 被引用文献数
- 7
Two kinds of reactions were carried out on the components of the seeds of Hernandia ovigera L. The reaction of lead tetraacetate on desoxypodophyllotoxin (I) and its analogous compounds caused the cleavage of methylenedioxyl group, affording the corresponding diphenols. In the case of 3, 4-methylenedioxypropylbenzene (XII), an intermediate acetoxyl compound (XIII) was isolated. The reactions of 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) on I and its analogous compounds afforded smoothly aromatized compounds. By the same reaction on bursehernin (III), cyclization and aromatization occurred simultaneously affording chinensin (XVIII) which was confirmed by direct comparison with authentic speciemen. The results of the cleavage reaction on I and XII by use of borontrichloride were also described.
- 著者
- 山口 秀夫 有本 正生 山本 起巳子 沼田 敦
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 薬学雑誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.6, pp.p674-677, 1979-06
- 被引用文献数
- 1
Four kinds of lignans were isolated from the seeds of Hernandia ovigera L. collected in Okinawa besides the previously reported desoxypodophyllotoxin (I). Oily substance II, named bursehernin, C_<21>H_<22>O_6,was confirmed to be lignan-2 isolated from Bursera schlechtendalii. III, mp 171-173°, and IV, mp 125-126°, were determined as desoxypicropodophyllin and podorhizol obtained from Podophyllum emodi WALL. respectively. V, mp 270-275°, could not be clarified due to its small amount.
- 著者
- 加島 竜彦 田ノ口 真理子 有本 正生 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.39, no.1, pp.192-194, 1991-01-25
(±)-Desoxypodophyllotoxin (2), a chief component of the seeds of Hernandia ovigera L., and (±)-β-peltatin-A methyl ether (3), an analogous phenyltetralin lignan, which have 2,3-trans, 3,4-cis configuration were synthesized according to the method developed for the synthesis of hernandin (1). The syntheses were pursued using the corresponding 4-phenyl-1,2-dihydronaphthalene lactones (9 and 10) followed by cleavage of the lactone moiety to give the unsaturated hydroxy acids (11 and 12). Subsequent hydrogenation and ring closure by means of p-toluenesulfonic acid afforded both 2,3-trans, 3,4-cis and 2,3-cis, 3,4-cis ligans (2 and 13 or 3 and 14), which were isolated by preparative thin layer chromatography.