Clark & Elbing LLP
Macrocyclization reactions and intermediates and other fragments useful in the synthesis of analogs of halichondrin B
The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.
EISAI R&D MANAGEMENT CO., LTD.
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Dae-Shik Hyeong-Wook Charles E. Francis G. Jaemoon
Kim Choi Chase Fang Lee