Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters

Daniele Fiorito, Selbi Keskin, Joseph M. Bateman, Malcolm George, Adam Noble, Varinder K. Aggarwal

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)
132 Downloads (Pure)

Abstract

Bastimolide B is a polyhydroxy macrolide isolated from marine cyanobacteria displaying antimalarial activity. It features a dense array of hydroxylated stereogenic centers with 1,5-relationships along a hydrocarbon chain. These 1,5-polyols represent a particularly challenging motif for synthesis, as the remote position of the stereocenters hampers stereocontrol. Herein, we present a strategy for 1,5-polyol stereocontrolled synthesis based on iterative boronic ester homologation with enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled from readily available building blocks with full control over the remote stereocenters, enabling the total synthesis to be completed in 16 steps (LLS).
Original languageEnglish
Pages (from-to) 7995−8001
Number of pages7
JournalJournal of the American Chemical Society
Volume144
Issue number18
Early online date2 May 2022
DOIs
Publication statusPublished - 11 May 2022

Bibliographical note

Funding Information:
D.F. thanks the Swiss National Science Foundation for an Early Postdoc Mobility Fellowship (P2GEP2_194799). S.K. thanks TUBITAK (The Scientific and Technological Research Council of Turkey) BIDEB-2219 international postdoctoral research fellowship programme for financial support. M.G. thanks the Bristol Chemical Synthesis Centre for Doctoral Training, funded by EPSRC (EP/S024107/1) and the University of Bristol for a PhD studentship. We thank Prof W. Gerwick (UC San Diego, Scripps institute of Oceanography) for providing the original NMR data of bastimolide B. We thank Prof. C. P. Butts and S. G. Aiken (University of Bristol) for fruitful scientific discussion and Siying Zhong for preliminary investigations into homologation with stannane 13 .

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

Structured keywords

  • BCS and TECS CDTs

Keywords

  • Organic compounds
  • Alcohols
  • Hydrocarbons
  • Chemical synthesis

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