A General Solution for Unstable Boronic Acids: Slow-Release Cross-Coupling from Air-Stable MIDA Boronates

Knapp, David M.; Gillis, Eric P.; Burke, Martin D.

doi:10.1021/ja901416p

Cited by 512 publications

(413 citation statements)

References 53 publications

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“…These sensitivities can be magnified considerably when specific functional groups have been deleted from the polyene macrolide skeleton, which has previously precluded the synthesis of some targeted AmB derivatives, including C35deOAmB (29). To improve the efficiency and flexibility with which such complex small molecules can be prepared, we have recently developed a simple and modular synthesis strategy, analogous to iterative peptide coupling, in which building blocks having all of the required functional groups preinstalled in the correct oxidation states and with the desired stereochemical relationships are sequentially linked via iterative application of one mild reaction (30)(31)(32)(33)(34)(35)(36)(37)(38). Enabling this approach, we discovered that N-methyliminodiacetic acid (MIDA) is a highly effective ligand for reversibly attenuating the reactivity of a boronic acid and thereby permitting the controlled sequential assembly of bifunctional haloboronic acids (Fig.…”

Section: Resultsmentioning

confidence: 99%

Amphotericin primarily kills yeast by simply binding ergosterol

Gray

Palacios

Dailey

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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498

408

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Amphotericin B (AmB) is a prototypical small molecule natural product that can form ion channels in living eukaryotic cells and has remained refractory to microbial resistance despite extensive clinical utilization in the treatment of life-threatening fungal infections for more than half a century. It is now widely accepted that AmB kills yeast primarily via channel-mediated membrane permeabilization. Enabled by the iterative cross-coupling-based synthesis of a functional group deficient derivative of this natural product, we have discovered that channel formation is not required for potent fungicidal activity. Alternatively, AmB primarily kills yeast by simply binding ergosterol, a lipid that is vital for many aspects of yeast cell physiology. Membrane permeabilization via channel formation represents a second complementary mechanism that further increases drug potency and the rate of yeast killing. Collectively, these findings (i) reveal that the binding of a physiologically important microbial lipid is a powerful and clinically validated antimicrobial strategy that may be inherently refractory to resistance, (ii) illuminate a more straightforward path to an improved therapeutic index for this clinically vital but also highly toxic antifungal agent, and (iii) suggest that the capacity for AmB to form proteinlike ion channels might be separable from its cytocidal effects.small molecules | protein-like functions | N-methyliminodiacetic acid boronates

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Section: Resultsmentioning

confidence: 99%

Amphotericin primarily kills yeast by simply binding ergosterol

Gray

Palacios

Dailey

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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498

408

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“…2-Pyridinylboronic acids and esters using halogen-metal exchange (HMe) are generally synthesized from 2-bromopyridines (3, X = 2-Br). 5,6,13,17,[34][35][36][37][38][39][40][41][42] In the particular case of compound 3 (X = 2-I), 2-iodopyridine was used. 16 To improve the stability (particularly in air and water), pyridine-2-boronates such as 6, 34 7, 35,36 and 8 37,38 were developed.…”

Section: The Synthesis Of Pyridinylboronic Acids and Esters By Halogementioning

confidence: 99%

Recent progress in the synthesis of pyridinylboronic acids and esters

Liu¹,

Milo²,

Lai

2013

Arkivoc

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Recent progress in the synthesis of (un)substituted pyridinylboronic acids and esters is reviewed. Five approaches to the synthesis of (un)substituted pyridinylboronic acids and esters are summarized: (1) halogen-metal exchange (HMe) and borylation, (2) metal-hydrogen exchange via directed ortho-metallation (DoM) followed by borylation, (3) palladium-catalyzed crosscoupling of halopyridines with tetraalkoxydiborane or dialkoxyhydroborane (4) iridium or rhodium catalyzed C-H or C-F borylation, and (5) exchange / borylation 2.1.1. The general procedure of halogen-metal (Li or Mg) exchange / borylation 2.1.2. The selectivity of halogen-metal (Li or Mg) exchange / borylation 2.1.3. The synthesis of 2-pyridinylboronic acids and esters by halogen-organometal (Li or Mg) exchange / borylation 2.1.4. The synthesis of pyridinediboronic acids via halogen-organotin (Sn) exchange / borylation 2.2. The synthesis of pyridinylboronic acids and esters by directed ortho-metalation (DoM) / borylation 2.2.1. The general procedure of directed ortho-metalation (DoM) / borylation 2.2.2. The selectivity of directed ortho-metalation (DoM) / borylation 2.3. The synthesis of pyridinylboronic acids and esters by palladium-catalyzed cross-coupling of halopyridines with tetraalkoxydiboron or dialkoxyhydroborane 2.4. The synthesis of pyridinylboronic acids and esters by iridium-or rhodium-catalyzed

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“…Of special promise are their biological [1][2][3], photophysical, and coordination [4][5][6][7][8] properties. Their use as chiral catalysts [9,10] is also of interest.The most frequently used methods for preparing (benzo)isoquinoline systems are cross-coupling reactions [11,12], which demand the use of special catalysts. We propose a method for preparing (benzo)isoquinoline derivatives based on an aza Diels-Alder reaction with 1,2,4-triazines as dienes and the aryne intermediates acting as dienophiles.…”

mentioning

confidence: 99%

“…The most frequently used methods for preparing (benzo)isoquinoline systems are cross-coupling reactions [11,12], which demand the use of special catalysts. We propose a method for preparing (benzo)isoquinoline derivatives based on an aza Diels-Alder reaction with 1,2,4-triazines as dienes and the aryne intermediates acting as dienophiles.…”

mentioning

confidence: 99%

Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

Kopchuk

Zyryanov

Коvalev

et al. 2013

Chem Heterocycl Comp

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(Benzo)isoquinoline derivatives are of significant interest in different areas of basic and applied organic chemistry. Of special promise are their biological [1][2][3], photophysical, and coordination [4][5][6][7][8] properties. Their use as chiral catalysts [9,10] is also of interest.The most frequently used methods for preparing (benzo)isoquinoline systems are cross-coupling reactions [11,12], which demand the use of special catalysts. We propose a method for preparing (benzo)isoquinoline derivatives based on an aza Diels-Alder reaction with 1,2,4-triazines as dienes and the aryne intermediates acting as dienophiles.The methodology for preparing diverse pyridine derivatives via reaction of the corresponding 1,2,4-triazines has long been known [13][14][15]. However, there are only a few examples of using aryne intermediates in similar reactions. The range of dienophiles in these cases is limited to certain dehydrobenzene derivatives, the generation of which used poorly available anthranilic acids [16,17] despite the marked growth in the chemistry of arynes in recent years [18,19].In our work, we propose a highly efficient method for the preparation of (het)aryl-substituted isoquinoline 1a and benzo[h]isoquinoline 1b, which involves the reaction of arynes 2a,b with the substituted 1,2,4-triazines 3a,b in anhydrous toluene for 24-36 h at 140°C under an argon atmosphere. The target compounds 1a,b were obtained in 76% and 80% yield, respectively. The corresponding arynes were generated in situ by the action of potassium tert-butoxide on the chloro-and bromo-substituted arenes 4a,b.The structure of the obtained compounds 1a,b was confirmed from the 1 H and 13 C NMR spectroscopy, mass spectrometry, and by elemental analysis data. The mass spectra of compounds 1a,b showed the presence of a molecular ion peak.The compounds obtained are 2,2'-bipyridine type ligands with an extended conjugated system, and are of interest from the viewpoint of complex formation and as luminescent materials.

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A General Solution for Unstable Boronic Acids: Slow-Release Cross-Coupling from Air-Stable MIDA Boronates

Cited by 512 publications

References 53 publications

Amphotericin primarily kills yeast by simply binding ergosterol

Amphotericin primarily kills yeast by simply binding ergosterol

Recent progress in the synthesis of pyridinylboronic acids and esters

Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

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