Pd/C-mediated depropargylation of propargyl ethers/amines in water

Rambabu, D.; Bhavani, S.; Swamy, Nalivela Kumara; Rao, Mandava V. Basaveswara; Pal, Manojit

doi:10.1016/j.tetlet.2012.12.093

Cited by 34 publications

(22 citation statements)

References 32 publications

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“…Figure 2d shows Pro-5FU completely disappeared from the crude mixture after 24 h, with 5FU being the major reaction product. In accordance with previous observations26, mass spectrometry analysis of the reaction crude indicated the formation of nontoxic 1-hydroxyacetone—a natural lipid metabolite also known as acetol29—as a byproduct from the oxidative cleavage of the propargyl group (Supplementary Fig. 2a,b).…”

Section: Resultssupporting

confidence: 91%

“…Dealkylated products were obtained within 24 h, indicating that this environmentally friendly methodology could be translated to other heterocyclic systems with lactam/lactim tautomery. Because of its implications for the bioorthogonal use of this novel masking/activation strategy, it is important to highlight that the palladium-mediated oxidative cleavage of the N -propargyl group in aqueous media results in the formation of non-toxic 1-hydroxyacetone 26 ( Supplementary Fig. 2b ).…”

Section: Discussionmentioning

confidence: 99%

“…These alkyl functional groups have been widely used in organic synthesis as OH protection strategies 20 and, importantly, recent studies have shown the sensitivity of allyl and propargyl phenolic ethers to oxidative cleavage by palladium species in biocompatible conditions 21 22 23 . Although palladium-mediated N -dealkylations typically require temperatures incompatible with cell survival (>80 °C) 24 25 26 , we hypothesized that the particular features of the 5FU heterocyclic system (relatively low p K a values because of the charge delocalization of 5FU aromatic conjugate bases 27 , Supplementary Fig. 1a ) could promote its properties as a leaving group relative to more basic amino groups.…”

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confidence: 99%

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Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

et al. 2014

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A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd0 catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd0-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd0-resin combination is due to the in situ generation of 5-fluorouracil. Pd0-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations.

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Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

et al. 2014

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“…The reaction seemed to proceed via generation of an active Pd(0) species from Pd/C that actually catalyze the C-C bond forming reaction between 3 and 4. Thus, the active Pd(0) species generated in situ (Prasad et al, 2012;Chen et al, 2007;Rambabu et al, 2013) (Scheme 3) undergoes oxidative addition with 4 to give E-1. The organoPd(II) species E-1 then undergoes trans organometallation with copper acetylide generated in situ from CuI and 3 to afford E-2.…”

Section: Chemistrymentioning

confidence: 99%

Mefenamic acid based novel indole analogues: Their synthesis and anti-proliferative effects

Babu

Ashfaq

Kumar

et al. 2019

Arabian Journal of Chemistry

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Prompted by the literature report on anticancer properties of mefenamic acid, a series of mefenamic acid based indole derivatives were designed via a rational approach. Synthesis of this class of compounds was carried out via a 3-step method starting from the mefenamic acid and using the Pd/C-Cu mediated coupling-cyclization strategy as a key step. A focused library of related molecules was synthesized and evaluated for their anti-proliferative properties against normal (HEK293T) and oral (CAL 27) as well as breast (MCF-7) cancer cell lines when several compounds showed selective growth inhibition of oral cancer cells of which the compound 5g [i.e. N-(2-(((5-fl uoro-1-(methylsulfonyl)-1H-indol-2-yl)methoxy)methyl)phenyl)-2,3-dimethylaniline] was found to be promising. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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“…These results indicated that the depropargylation reaction can be catalyzed via Pd(II)-catalyzed hydration intermediates, but also via allenylpalladium resulting from the oxidative addition of Pd(0). [33,53,54] …”

Section: 1mentioning

confidence: 99%

A Turn‐On Fluorescent Probe for Highly Selective and Sensitive Detection of Palladium

et al. 2016

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Pd/C-mediated depropargylation of propargyl ethers/amines in water

Cited by 34 publications

References 32 publications

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

Mefenamic acid based novel indole analogues: Their synthesis and anti-proliferative effects

A Turn‐On Fluorescent Probe for Highly Selective and Sensitive Detection of Palladium

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