155252-36-1Relevant academic research and scientific papers
Hemi-synthesis and biological activity of new analogues of podophyllotoxin
Roulland, Emmanuel,Magiatis, Prokopios,Arimondo, Paola,Bertounesque, Emmanuel,Monneret, Claude
, p. 3463 - 3471 (2007/10/03)
Various 4-analogues of podophyllotoxin and epipodophyllotoxin were obtained via the formation of the corresponding 4-keto derivatives. Methyloximation of podophyllotoxone, followed by subsequent catalytic hydrogenation, gave stereoselective access to 4-α-amino-4-deoxypodophyllotoxin and from there, to the corresponding acetamido and formamido derivatives. Base-catalyzed isomerisation of 4-α-amino-4-deoxypodophyllotoxin led to the corresponding picropodophyllin isomer while the 4-β-amino afforded a neopodophyllotoxin-like derivative. On the other hand, oxirane and hydroxymethyl-containing analogues were prepared from podophyllotoxin and 4-epi-4′-demethyl-podophyllotoxin, using a Takai olefination strategy. In the latter series, carboxaldehyde- and carboxylic acid-containing derivatives were also synthesized.
New compounds related to podophyllotoxin and congeners: synthesis, structure elucidation and biological testing.
Hansen,Jensen,Willumsen,Norskov-Lauritsen,Ebbesen,Nielsen,Buchardt
, p. 1190 - 1200 (2007/10/02)
4-Azido, 4-amino, 4-amido and 4-alkoxy compounds related to the lignans podophyllotoxin and 4'-demethylepipodophyllotoxin have been synthesized, and their structures elucidated. The Ritter reaction was shown to be useful in the preparation of the 4-amido compounds with the required stereochemistry. A preparative method for 4-chloro-4-deoxypicrophyllotoxin, for which all earlier synthetic attempts resulted in the two dehydrated compounds, alpha- and beta-apopicropodophyllotoxin, was developed. Supplementary preliminary studies of the biological activities of some of the compounds were performed. All compounds had pronounced inhibitory effect on the in vitro growth of human cervical cancer cells and TC-mouse cells with 4-amino-4-deoxypodophyllotoxin and 4-azido-4-deoxypodophyllotoxin showing the highest activity. Alkaline elution studies indicate that the toxicity of the 4'-demethoxy derivatives is due to protein-mediated DNA nicking. None of the compounds were found to have antiviral effect against herpes simplex type 2 (HSV-2), human immunodeficiency (HIV), and cytomegalovirus (CMV) in doses not toxic to the cells.
