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).