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. 2022 May 11;144(18):7995-8001.
doi: 10.1021/jacs.2c03192. Epub 2022 May 2.

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

Daniele Fiorito  1 , Selbi Keskin  1 , Joseph M Bateman  1 , Malcolm George  1 , Adam Noble  1 , Varinder K Aggarwal  1
Affiliations

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

Daniele Fiorito et al. J Am Chem Soc. .

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).

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Iterative strategies toward the stereocontrolled synthesis of polyols.
Scheme 1
Scheme 1. Retrosynthetic Approach to Bastimolide B
Scheme 2
Scheme 2. Synthesis of Fragments A (4) and B (5)
Scheme 3
Scheme 3. Study of Effects of Substrate Control on Asymmetric Lithiation
Scheme 4
Scheme 4. Fragment Coupling and Completion of the Synthesis of Bastimolide B
See this image and copyright information in PMC

References

    1. Staunton J.; Weissman K. J. Polyketide Biosynthesis: A Millennium Review. Nat. Prod. Rep. 2001, 18, 380. 10.1039/a909079g. - DOI - PubMed
    2. Newman D. J.; Cragg G. M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770. 10.1021/acs.jnatprod.9b01285. - DOI - PubMed
    1. Yeung K.-S.; Paterson I. Advances in the Total Synthesis of Biologically Important Marine Macrolides. Chem. Rev. 2005, 105, 4237. 10.1021/cr040614c. - DOI - PubMed
    2. Lorente A.; Lamariano-Merketegi J.; Albericio F.; Á lvarez M. Tetrahydrofuran-Containing Macrolides: a Fascinating Gift from the Deep Sea. Chem. Rev. 2013, 113, 4567. 10.1021/cr3004778. - DOI - PubMed
    3. Liu H.; Lin S.; Jacobsen K. M.; Poulsen T. B. Chemical Syntheses and Chemical Biology of Carboxyl Polyether Ionophores: Recent Highlights. Angew. Chem., Int. Ed. 2019, 58, 13630. 10.1002/anie.201812982. - DOI - PubMed
    1. Schetter B.; Mahrwald R. Modern Aldol Methods for the Total Synthesis of Polyketides. Angew. Chem., Int. Ed. 2006, 45, 7506. 10.1002/anie.200602780. - DOI - PubMed
    2. Kan S. B. J.; Ng K. K.-H.; Paterson I. The Impact of the Mukaiyama Aldol Reaction in Total Synthesis. Angew. Chem., Int. Ed. 2013, 52, 9097. 10.1002/anie.201303914. - DOI - PubMed
    3. Gati W.; Yamamoto H. Second Generation of Aldol Reaction. Acc. Chem. Res. 2016, 49, 1757. 10.1021/acs.accounts.6b00243. - DOI - PubMed
    1. Smith A. B. III; Wuest W. M. Evolution of Multi-Component Anion Relay Chemistry (ARC): Construction of Architecturally Complex Natural and Unnatural Products. Chem. Commun. 2008, 5883. 10.1039/b810394a. - DOI - PMC - PubMed
    2. Deng Y.; Smith A. B. III Evolution of Anion Relay Chemistry: Construction of Architecturally Complex Natural Products. Acc. Chem. Res. 2020, 53, 988. 10.1021/acs.accounts.0c00076. - DOI - PMC - PubMed
    1. Yus M.; González-Gómez J. C.; Foubelo F. Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products. Chem. Rev. 2013, 113, 5595. 10.1021/cr400008h. - DOI - PubMed
    2. Boiarska Z.; Braga T.; Silvani A.; Passarella D. Brown Allylation: Application to the Synthesis of Natural Products. Eur. J. Org. Chem. 2021, 2021, 3214. 10.1002/ejoc.202100258. - DOI

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