103614-76-2Relevant articles and documents
A Reverse Approach to the Total Synthesis of Halichondrin B
Nicolaou,Pan, Saiyong,Shelke, Yogesh,Das, Dipendu,Ye, Qiuji,Lu, Yong,Sau, Susanta,Bao, Ruiyang,Rigol, Stephan
supporting information, p. 9267 - 9276 (2021/07/01)
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.
Unified, Efficient, and Scalable Synthesis of Halichondrins: Zirconium/Nickel-Mediated One-Pot Ketone Synthesis as the Final Coupling Reaction
Yahata, Kenzo,Ye, Ning,Ai, Yanran,Iso, Kentaro,Kishi, Yoshito
supporting information, p. 10796 - 10800 (2017/08/30)
Unified, efficient, and scalable syntheses of the halichondrin natural products are reported. A newly developed Zr/Ni-mediated one-pot ketone synthesis was used to couple the two halves of the final product at a late stage in the synthesis. With the use of a slight excess of the left halves, the desired ketones were isolated in yields of 80–90 %. The halichondrins were obtained from these ketones in two steps, namely desilylation and [5,5]-spiroketal formation. The new synthetic route was effective for the total synthesis of all members in the homohalichondrin subgroup. The scalability of this process was demonstrated with halichondrin B; 150 mg of halichondrin B (68 % overall yield) were obtained from 200 mg of the right-half precursor.
