Total synthesis of 5-N-acetylardeemin and amauromine: Practical routes to potential MDR reversal agents Journal Article

  


Authors: Depew, K. M.; Marsden, S. P.; Zatorska, D.; Zatorski, A.; Bornmann, W. G.; Danishefsky, S. J.
Article Title: Total synthesis of 5-N-acetylardeemin and amauromine: Practical routes to potential MDR reversal agents
Abstract: The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 → 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 → 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.
Keywords: unclassified drug; doxorubicin; nonhuman; paclitaxel; mouse; animal experiment; animal model; cytotoxicity; drug synthesis; vinblastine; cyclization; oxidation; chemical reaction; multidrug resistance; stereochemistry; alkaloid derivative; article; 5 n acetylardeemin; amauromine
Journal Title: Journal of the American Chemical Society
Volume: 121
Issue: 51
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 1999-12-29
Start Page: 11953
End Page: 11963
Language: English
DOI: 10.1021/ja991558d
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033616097&partnerID=40&md5=fe3860ffa42e01bfe8b5eeca8c5903a7
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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MSK Authors
  1. William Bornmann
    112 Bornmann
  2. Andrzej Zatorski
    23 Zatorski
  3. Samuel J Danishefsky
    539 Danishefsky
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