Synthesis of navelbine analogs

Details Synthesis of navelbine analogs Synthesis of navelbine analogs

1991-07-29

1993-06-15

Berch, Mark L.

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

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

546 51, 546201, C07D46100, C07D22700, C07B 4900

Patent

active

052200167

ABSTRACT:
The invention is a de novo synthesis of the norcatharanthine moiety of navelbine. The synthesis includes condensing a Grignard reagent prepared from an amine-protected R(+)-piperidinyl methanol with an N-protected 2-methoxyoxalyl indole. The indole N-protecting group is removed to provide a 2-methoxyindole hydroxy ester which is coupled to vindoline. After removal of the amineprotecting group from the piperidinyl group, ring closure to the indole moiety provides dihydrodesethyl navelbine. Other derivatives and analogs of navelbine with potential clinical applications in cancer chemotherapy may be readily synthesized. The synthesis opens a route to a wide variety of navelbine modifications, including modifications at or near the tryptamine bridge.

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