著者

川松 豊 杉原 弘貞 佐々木 希吉 森本 浩

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.13, pp.99-106, 1969-09-01

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I. Synthesis of 2,3-dialkoxy-5-alkyl-1,4-benzoquinone a) 4a and 4b obtained from 1 were oxidized with organic peracids to give 2,3-dimethoxy-(5a) and 2,3-diethoxy-5-methyl-1,4-benzoquinone (5b). b) 9a and 9b obtained from 6 were oxidized in a similar manner to give 5a and 10. II. Synthesis of isoprenoid quinones The authors found two new condensation methods. a) Method using an N-sulfinylamine. A solution of hydroquinone (12), methyl N-sulfinylanthranilate (14) and phytol (13) in dioxane was heated and oxidized with ferric chloride to give 2,3-dimethoxy-5-methyl-6-phytyl-1,4-benzoquinone (15) as well as by-products 16 and 17. The structures of 16 and 17 were made clear and the reaction mechanism was discussed. The results are shown in Table 1. b) Method using a metal. A solution of 5a and X-CH_2-CH=C-CH_3-CH_2-R in petroleum ether was treated with slightly an excess amount of amalgamated zinc at the room temperature to give 18. The product 18 was obtained also from hydroquinone (12). The reaction mechanism and the results are shown in Table 2. III. Stereochemistry of isoprenoid quinones It has been so far known that the steric configuration of the side chain of naturally occurring isoprenoid quinones is all-trans, but synthesized isoprenoid quinones inevitably contain a small amount of the cis-isomer. Then, the authors separated these isomers by the column chromatography to confirm their yields and to compare their NMR spectra with each other. The relationship between the structures of the quinones and the biological activity is also mentioned.

著者

川松 豊 杉原 弘貞 佐々木 希吉 森本 浩

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.13, pp.99-106, 1969

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I. Synthesis of 2,3-dialkoxy-5-alkyl-1,4-benzoquinone a) 4a and 4b obtained from 1 were oxidized with organic peracids to give 2,3-dimethoxy-(5a) and 2,3-diethoxy-5-methyl-1,4-benzoquinone (5b). b) 9a and 9b obtained from 6 were oxidized in a similar manner to give 5a and 10. II. Synthesis of isoprenoid quinones The authors found two new condensation methods. a) Method using an N-sulfinylamine. A solution of hydroquinone (12), methyl N-sulfinylanthranilate (14) and phytol (13) in dioxane was heated and oxidized with ferric chloride to give 2,3-dimethoxy-5-methyl-6-phytyl-1,4-benzoquinone (15) as well as by-products 16 and 17. The structures of 16 and 17 were made clear and the reaction mechanism was discussed. The results are shown in Table 1. b) Method using a metal. A solution of 5a and X-CH_2-CH=C-CH_3-CH_2-R in petroleum ether was treated with slightly an excess amount of amalgamated zinc at the room temperature to give 18. The product 18 was obtained also from hydroquinone (12). The reaction mechanism and the results are shown in Table 2. III. Stereochemistry of isoprenoid quinones It has been so far known that the steric configuration of the side chain of naturally occurring isoprenoid quinones is all-trans, but synthesized isoprenoid quinones inevitably contain a small amount of the cis-isomer. Then, the authors separated these isomers by the column chromatography to confirm their yields and to compare their NMR spectra with each other. The relationship between the structures of the quinones and the biological activity is also mentioned.

著者

左右田 隆 川松 豊 藤田 剛 目黒 寛司 池田 衡

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.122, no.11, pp.909-918, 2002-11-01 (Released:2003-02-18)

参考文献数

37

被引用文献数

8 11

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Insulin resistance is a characteristic feature of type II diabetes as well as obesity. This insulin resistant state at the peripheral tissue level causes impaired glucose utilization, leading to hyperglycemia. Studies of antidiabetic agents by Takeda originated more than three decades ago when KK mice were introduced, followed by the development of a highly insulin-resistant animal model, KKAy mice. The first 2,4-thiazolidinedione derivative AL-321, which exhibited hypoglycemic effects in KKAy mice, was discovered by modification of the hypolipidemic agent AL-294 as a lead compound. Extensive structure-activity relationship studies on the analogues of AL-321 led to the selection of ciglitazone (ADD-3878) as a candidate for clinical evaluation. Ciglitazone, a prototypical compound in the series, was shown to normalize hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in various insulin-resistant animal models without altering normoglycemia in nondiabetic animal models. However, it appeared that a more potent compound was needed for further clinical evaluation of this class of compound. Further study of this series of compounds led to the finding of pioglitazone (AD-4833) as a promising clinical candidate. Pioglitazone clearly ameliorates the abnormal glucose and lipid metabolism in diabetic patients and was marketed in the USA in August 1999 for the treatment of type II diabetes. Pioglitazone is now marketed in more than 40 countries world wide. Historical aspects of our studies on pioglitazone and its biological activities are described.