Document Detail


Hemi-synthesis and biological activity of new analogues of podophyllotoxin.
MedLine Citation:
PMID:  12213460     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-alpha-amino-4-deoxypodophyllotoxin and from there, to the corresponding acetamido and formamido derivatives. Base-catalyzed isomerisation of 4-alpha-amino-4-deoxypodophyllotoxin led to the corresponding picropodophyllin isomer while the 4-beta-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.
Authors:
Emmanuel Roulland; Prokopios Magiatis; Paola Arimondo; Emmanuel Bertounesque; Claude Monneret
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  10     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-09-05     Completed Date:  2003-03-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  3463-71     Citation Subset:  IM    
Affiliation:
Laboratoire de Pharmacochimie, UMR 176 CNRS-IC, Section Recherche de l'Institut Curie, 26 rue d'Ulm, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / chemical synthesis,  pharmacology
Animals
Antineoplastic Agents, Phytogenic / chemical synthesis*,  pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
DNA Topoisomerases, Type I / antagonists & inhibitors
Enzyme Inhibitors / chemical synthesis,  pharmacology
Humans
Leukemia L1210 / drug therapy
Necrosis
Podophyllotoxin / analogs & derivatives*,  chemical synthesis*,  pharmacology
Stereoisomerism
Structure-Activity Relationship
Swine
Tubulin / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antineoplastic Agents, Phytogenic; 0/Enzyme Inhibitors; 0/Tubulin; 518-28-5/Podophyllotoxin; EC 5.99.1.2/DNA Topoisomerases, Type I

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