A Reverse Approach to the Total Synthesis of Halichondrin B.

Journal of the American Chemical Society
K C NicolaouStephan Rigol

Abstract

A new strategy is described for the total synthesis of halichondrin B featuring reversal of the sequential construction of a number of its cyclic ethers from the classical approach by instead forming C-O bonds first followed by C-C bond formation. Employing the Nicholas reaction to generate linear ethers as precursors for the total synthesis of halichondrin B and other members of the halichondrin and eribulin families of compounds, this novel approach provides new opportunities for the development of improved syntheses of these complex and valuable compounds. In this Article, we report the syntheses of defined fragments I, MN, EFG, and A. Fragments I and MN were then coupled and elaborated to advanced intermediate IJKLMN, which was joined with fragment EFG to afford, after appropriate elaboration and macrolactonization, the more advanced polycyclic intermediate EFGHIJKLMN. Elaboration of the latter and coupling with fragment A followed by further functionalization completed the total synthesis of halichondrin B through a short and convergent pathway.

References

Jun 8, 2000·Bioorganic & Medicinal Chemistry Letters·Y WangM J Yu
Jun 24, 2000·The Journal of Organic Chemistry·S D BurkeJ J Klovning
Feb 24, 2001·Chemistry : a European Journal·T M Kamenecka, S J Danishefsky
Sep 2, 2003·Angewandte Chemie·David R WilliamsSamarjit Patnaik
Oct 16, 2004·Bioorganic & Medicinal Chemistry Letters·Boris M SeletskyMelvin J Yu
Nov 5, 2005·The Journal of Organic Chemistry·William T LambertSteven D Burke
Dec 15, 2005·Chemical Reviews·Tadashi Nakata
Dec 15, 2005·Chemical Reviews·Masayuki Inoue
Aug 21, 2007·Bioorganic & Medicinal Chemistry Letters·Kyoji FurutaMasaaki Suzuki
Jul 24, 2008·Journal of the American Chemical Society·K C NicolaouDennis R Burton
Sep 4, 2008·Angewandte Chemie·K C NicolaouRobert J Aversa
Feb 13, 2009·Angewandte Chemie·Katrina L JacksonAndrew J Phillips
Apr 23, 2009·Chemical Reviews·K C Kumara SwamyK V P Pavan Kumar
Jun 19, 2009·Chemical Reviews·Katrina L JacksonAndrew J Phillips
Oct 8, 2009·Journal of the American Chemical Society·Dae-Shik KimYoshito Kishi
Feb 18, 2011·Bioorganic & Medicinal Chemistry Letters·Sridhar NarayanMelvin J Yu
Feb 24, 2011·The Journal of Organic Chemistry·Baudouin GerardLisa A Marcaurelle
Nov 15, 2011·The Journal of Organic Chemistry·Michael C McLeodMargaret A Brimble
Dec 23, 2011·Journal of the American Chemical Society·Akihiko YamamotoYoshito Kishi
Mar 13, 2014·Journal of the American Chemical Society·Atsushi UedaYoshito Kishi
May 20, 2017·Chemical Reviews·Joshua E ZweigTimothy R Newhouse
Jun 19, 2019·Scientific Reports·Satoshi KawanoYoshito Kishi
Aug 14, 2020·Journal of the American Chemical Society·Vemula Praveen Kumar, Yoshito Kishi

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Citations

Dec 2, 2021·Journal of the American Chemical Society·K C NicolaouStephan Rigol

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