著者

西村 吉雄

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.45, no.9, pp.873-887, 1987-09-01 (Released:2009-11-13)

参考文献数

81

被引用文献数

2 3

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This article describes the syntheses and the relationships between structure and antitumor activity of pyrrolizidine alkaloid (indicine N-oxide), lignan lactone glycoside (etoposide) and their related compounds from the standpoint of diastereomer and enantiomer.Total syntheses of indicine N-oxide, its diastereomer (intermedine N-oxide) and their enantiomers have been achieved in a totally stereospecific fashion through a sequence involving as the key steps (a) the enantioselective synthesis of retronecine and its enantiomer, (b) the enantioselective synthesis of (+) -trachelanthic acid and its enantiomer, and (c) a combination of each segments.Syntheses of all four possible diastereomers of etoposide and its aminoglycosidic analogues have been achieved via optical resolution of (±) -podophyllotoxin by glycosidation with D- and L-sugars.

著者

西村 吉雄 齋藤 仁 好川 博 近藤 信一 竹内 富雄

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 30 (ISSN:24331856)

巻号頁・発行日

pp.508-515, 1988-09-26 (Released:2017-08-18)

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The semi-synthetic podophyllotoxin glycosides, VP-16-213 (1) and VM-26 (2) showing a marked clinical efficacy and the intriguing mechanisms of action have stimulated interest in the synthesis of new active analogues of the podophyllotoxin glycoside. The systematic chemical modification of podophyllotoxins was studied. 1) Aminoglycosidic lignan variants (6, 7, etc.) of 4'-O-demethy1-1-epipodophyllotoxin were synthesized by a stereoselective BF_3-catalyzed coupling of 5 with the corresponding aminosugar derivatives. N-Alkylaminoglycosyl analogues (8, etc.) of 1 were also derived from 6. 2) Syntheses of all possible diastereomers (1, 6, 8, and 15-23) of 1, 6 and 8 were achieved via optical resolution of (±)-podophyllotoxin by glycosidation with D- and L-sugars. 3) Glycosidic variants of 1-β-hydroxy-α-peltatin and 1-β-hydroxy-8-O-methyl-a-peltatin (24-26) were synthesized by glycosidation of 28 and 29 with the corresponding sugar derivatives. 4) The syntheses of carbocyclic lignan variants (34-37) of 4'-O-demethyl-1-epipodophyllotoxin were achieved by coupling of 5 with chiral aminocyclitols. 5) 1-O-(2-Aminoethyl) ethers of 4'-O-demethyl-1-epipodophyllotoxin (38-42, etc.) were synthesized by coupling of 5 with the corresponding 2-aminoethanol derivatives, and with ethylene glycol followed by reductive amination of its aldehyde. Among all derivatives synthesized, 6 and 8 were found to have superior antitumor activity to 1.

著者

斉藤 仁 好川 博 西村 吉雄 近藤 信一 竹内 富雄 梅澤 濱夫

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.9, pp.3741-3746, 1986-09-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

17 25

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D-(and L-)2, 6-Dideoxy-2-aminoglycosidic variants of 4'-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4'-O-benzyloxycarbonyl- or 4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (6 or 14) with the corresponding aminosugar derivatives. 1-O-(2-Amino-2-deoxy-4 : 6-O-ethylidene-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (18) reacted with aldehydes in the presence of sodium cyanoborohydride, or reacted with α, β-unsaturated esters, or with α, β-unsaturated nitriles to yield the corresponding N-alkyl analogs. A number of the 4'-O-demethyl-1-epipodopyllotoxin β-D-aminoglycoside derivatives gave significant survival time increases in mice with leukemia L-1210. In particular, 1-O-(2-dimethylamino-2-deoxy-4 : 6-O-ethylidene-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (19) showed superior activity to VP-16-213 (etoposide, 1).

著者

斉藤 仁 好川 博 西村 吉雄 近藤 信一 竹内 富雄 梅澤 濱夫

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.9, pp.3733-3740, 1986-09-25 (Released:2008-03-31)

参考文献数

42

被引用文献数

8 14

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D-(and L-)Aminoglycosidic variants of 4'-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4'-O-benzyloxycarbonyl- or 4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (8 or 22) with the corresponding aminosugar derivatives. Cyclic acetals of 1-O-(2-amino-2-deoxy- and 3-amino-3-deoxy-β-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxins (13 and 21) gave a significant survival time increase in mice with leukemia L-1210, and showed superior activity to VP-16-213 (etoposide, 5).

著者

西村 吉雄

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.55, no.2, pp.142-151, 1997-02-01 (Released:2009-11-16)

参考文献数

42

被引用文献数

1 1

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Specific inhibitors of glycosidases are aiding in unraveling how oligosaccharides of glycoconjugates, as the functional domains for carbohydrate-protein interactions, regulate biological functions, and how they produce beneficial pharmaceutical effects in the prevention and treatment of a variety of diseases.This paper describes the progress of the synthesis of iminosugar glycosidase inhibitors, siastatin B analogues toward the rational drug design of D-glucuronic acid and L-iduronic acid-based inhibitors for tumor invasion, and of sialic acid-based inhibitors for the influenza virus sialidase, as well as indicating progress in the development of a new therapeutic and prophylactic treatment for tumor metastasis and influenza infection.