77421-36-4Relevant articles and documents
Synthetic and mechanistic studies on the azabicyclo[7.3.1]enediyne core and naphtho[2,3-h]quinoline portions of dynemicin A
Magnus, Philip,Eisenbeis, Shane A.,Fairhurst, Robin A.,Iliadis, Theodore,Magnus, Nicholas A.,Parry, David
, p. 5591 - 5605 (2007/10/03)
The synthesis of the 13-keto-10-azabicyclo[7.3.1]enediyne core structure of dynemicin A has been achieved by two routes, Schemes 4 and 6. The chemistry of the 13-keto core structure is dominated by the unusually facile bridgehead enolization. Comparison of the rates of cycloaromatization of a variety of enediynes revealed that substantial rate differences occurred even though the distance between the bonding acetylenes was virtually identical. A non-radical cycloaromatization pathway, initiated by thiol addition to the enediyne system, was discovered, and the simple core amine 26 exhibits modest in vitro and in vivo antitumor activity. Finally, two methods for the synthesis of the naphtho[2,3-h]quinoline portion of dynemicin A are described, and both these compounds also exhibit antitumor activity.
Synthesis of tetrahydroquinoline enediyne core analogs of dynemicin
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, (2008/06/13)
A process is described for the preparation of the core azobicyclo[7.3.1]tridecaenediyne moiety of the antitumor antibiotic dynemicin. The synthesis allows efficient production of the enediyne as a stable, compound in good yield from the adamantyl N-protected azabicyclo[7.3.1]tridecadiyne. The adamantyl protecting group is employed in the starting material, N-adamantyl dihydroquinoline or N-adamantyl 6-methoxy quinoline. Also disclosed are process for the synthesis of 3-hydroxy-6-methoxyquinoline and several N-substituted derivatives of azobicyclo[7.3.1]tridecaenediyne. Solid tumor and leukemia assays were performed on the analogs of dynemicin. The results suggest a method that these compounds will useful in treating certain types of leukemias and solid tumors. The disclosed synthesis provides a route to new dynemicin intermediates and analogs which will allow development of second and third generation dynemicins.
Short Synthesis of the Dynemicin Core Structure: Unusual Bridgehead Enolate Raectivity
Magnus, Philip,Parry, David,Iliadis, Theodore,Eisenbeis, Shane A.,Fairhurst, Robin A.
, p. 1543 - 1544 (2007/10/02)
The dynemicin core azabicycloenediyne 2 is readily synthesized in five steps from the quinolines 9 or 13; the chemistry of the core enediyne is dominated by its ready enolization.
