Alkyl Boronic Acid Synthesis Essay

(Phys.org)—A team of researchers from the Scripps Research Institute has developed a simple, practical method for converting carboxylic acids into boronate esters and boronic acids. In their paper published in the journal Science, the team describes the process and why they believe it will make such compounds more accessible.

Carboxylic acids are acids that belong, quite naturally, to the carboxyl group, which consists of double-bonded carbon atoms to a single oxygen atom and singly bonded to a member of a hydroxyl group. They are used in a variety of manufacturing processes, most often as part of a reaction that produces other compounds such as boronate esters and boronic acids (alkyls or aryl substituted boric acids that have a carbon–boron bond). End products include things like soaps, soft drinks, food products and some drugs, such as the cancer therapy Velcade. But as the researchers note, until now, the process has involved converting such acids to more useful compounds in ways they describe as non-trivial. In this new effort, the researchers describe a technique to convert such acids to boronate esters and boronic acids that is practical and relatively simple.

To convert a carboxylic acid to a boron compound, the researchers started by converting it to a redox-active N-hydroxyphthalimide ester. A nickel catalyst was then used to induce decarboxylative borylation in the presence of bis(pinacolato)diboron, a bipyridine ligand to produce a boronate ester, which was then hydrolyzed. They note the technique works equally well on a host of tertiary carboxylic acids and even peptides. They also point out that it can be used in late-stage transformations of complex molecules, making it useful in a particularly broad range of applications.

To prove its value, the team worked with a group at Calibr, and together they used the technique to create analogs of human neutrophil elastase inhibitors, which are used to treat lung diseases. Calibr has been looking for a way overcome potency issues, and report that the new technique resulted in compounds that were much more potent than those made the traditional way.

The new technique is relatively straightforward, which means it will likely be tried and adapted first in laboratories around the world, and then put into production processes relatively quickly, possibly reducing costs.

Explore further:B3NO2 ring system serves as a versatile catalyst for amide bond formation

More information: Chao Li et al. Decarboxylative borylation, Science (2017). DOI: 10.1126/science.aam7355

Abstract
The widespread use of alkyl boronic acids and esters is frequently hampered by the challenges associated with their preparation. Herein we describe a simple and practical method to rapidly access densely functionalized alkyl boronate esters from abundant carboxylic substituents. This broad-scope Ni-catalyzed reaction uses the same activating principle as amide bond formation to replace a carboxylic acid with a boronate ester. Application to peptides allowed expedient preparations of α-amino boronic acids, often with high stereoselectivity, facilitating the synthesis of both FDA approved alkyl boronic acid drugs (Velcade and Ninlaro) as well as a boronic acid version of the iconic antibiotic vancomycin. The reaction also enabled the discovery and extensive biological characterization of potent elastase inhibitors which may have a strategic advantage due to their covalent-reversible binding properties.

Press release

Journal reference:Science

© 2017 Phys.org

Citation data is made available by participants in Crossref's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search inSciFinder.

  • Tetramethyl Orthosilicate (TMOS) as a Reagent for Direct Amidation of Carboxylic Acids

    D. ChristopherBraddockPaul D.LickissBen C.RowleyDavidPughTeresaPurnomoGajanSanthakumarSteven J.Fussell

    Organic Letters201820 (4), 950-953

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Catalytic Oligopeptide Synthesis

    ZijianLiuHidetoshiNodaMasakatsuShibasakiNaoyaKumagai

    Organic Letters201820 (3), 612-615

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Boronic Acid Accelerated Three-Component Reaction for the Synthesis of α-Sulfanyl-Substituted Indole-3-acetic Acids

    AmritaDasKenjiWatanabeHiroyukiMorimotoTakashiOhshima

    Organic Letters201719 (21), 5794-5797

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Nonclassical Routes for Amide Bond Formation

    Renata Marciade FigueiredoJean-SimonSuppoJean-MarcCampagne

    Chemical Reviews2016116 (19), 12029-12122

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Lewis Acids

    ManabuHatanoKazuakiIshihara

    2016,27-66

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis

    TharwatMohy El DineWilliamErbYohannBerhaultJacquesRoudenJérômeBlanchet

    The Journal of Organic Chemistry201580 (9), 4532-4544

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • A Dual Arylboronic Acid–Aminothiourea Catalytic System for the Asymmetric Intramolecular Hetero-Michael Reaction of α,β-Unsaturated Carboxylic Acids

    TakumiAzumaAkihiroMurataYusukeKobayashiTsubasaInokumaYoshijiTakemoto

    Organic Letters201416 (16), 4256-4259

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • A Highly Efficient Asymmetric Synthesis of Vernakalant

    JohnLimantoEric R.AshleyJingjunYinGregory L.BeutnerBrendan T.GrauAmude M.KassimMary M.KimArtisKlaparsZhijianLiuHallena R.StrotmanMatthew D.Truppo

    Organic Letters201416 (10), 2716-2719

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Lanthanum(III) Triflate Catalyzed Direct Amidation of Esters

    HiroyukiMorimotoRisaFujiwaraYuheiShimizuKazuhiroMorisakiTakashiOhshima

    Organic Letters201416 (7), 2018-2021

    Abstract | Full Text HTML | PDF | PDF w/ Links

  • Mechanistic insights into boron-catalysed direct amidation reactions

    SergeyArkhipenkoMarco T.Sabatini

  • Categories: 1

    0 Replies to “Alkyl Boronic Acid Synthesis Essay”

    Leave a comment

    L'indirizzo email non verrà pubblicato. I campi obbligatori sono contrassegnati *