Synthesis of tetrahydroquinoline enediyne core analogs of dynemi

Details Synthesis of tetrahydroquinoline enediyne core analogs of dynemi Synthesis of tetrahydroquinoline enediyne core analogs of dynemi

1993-09-09

1995-08-15

Rotman, Alan L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546 79, 546152, C07F 702, C07D22106, C07D22122

Patent

active

054420652

ABSTRACT:
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.

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