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

[Image: see text] 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...

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Autores principales: Fiorito, Daniele, Keskin, Selbi, Bateman, Joseph M., George, Malcolm, Noble, Adam, Aggarwal, Varinder K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100475/
https://www.ncbi.nlm.nih.gov/pubmed/35499478
http://dx.doi.org/10.1021/jacs.2c03192
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author Fiorito, Daniele
Keskin, Selbi
Bateman, Joseph M.
George, Malcolm
Noble, Adam
Aggarwal, Varinder K.
author_facet Fiorito, Daniele
Keskin, Selbi
Bateman, Joseph M.
George, Malcolm
Noble, Adam
Aggarwal, Varinder K.
author_sort Fiorito, Daniele
collection PubMed
description [Image: see text] 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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spelling pubmed-91004752022-05-14 Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters Fiorito, Daniele Keskin, Selbi Bateman, Joseph M. George, Malcolm Noble, Adam Aggarwal, Varinder K. J Am Chem Soc [Image: see text] 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). American Chemical Society 2022-05-02 2022-05-11 /pmc/articles/PMC9100475/ /pubmed/35499478 http://dx.doi.org/10.1021/jacs.2c03192 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Fiorito, Daniele
Keskin, Selbi
Bateman, Joseph M.
George, Malcolm
Noble, Adam
Aggarwal, Varinder K.
Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title_full Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title_fullStr Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title_full_unstemmed Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title_short Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters
title_sort stereocontrolled total synthesis of bastimolide b using iterative homologation of boronic esters
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100475/
https://www.ncbi.nlm.nih.gov/pubmed/35499478
http://dx.doi.org/10.1021/jacs.2c03192
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