1,3-Dimethyl-2-(3-nitro-1,2,4-triazol-1-yl)-2-pyrrolidin-1-yl-1,3,2-diazaphospholidinium hexafluorophosphate (MNTP): a powerful condensing reagent for phosphate and phosphonate esters

Oka, Natsuhisa; Shimizu, Mamoru; Saigo, Kazuhiko; Wada, Takehiko

doi:10.1016/j.tet.2006.01.084

Cited by 33 publications

(28 citation statements)

References 34 publications

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“…The progression of the reaction was followed by 31 P NMR spectroscopy either by performing the H-phosphonate coupling in the NMR tube (CD 3 CN) or by NMR spectroscopic analysis of a small aliquot of the reaction mixture. The reaction is supposed to proceed through formation of the reactive tetracoordinated P III -intermediates such as H-pyrophosphonates[ 49 ] and nitrotriazol-1-yl-phosphites,[ 50 ] which can be detected by 31 P NMR spectroscopy in the absence of hydroxylic component. Upon shortage of nucleophilic component 27 , activation of Ara4N H-phosphonate 6 resulted in eventual formation of nitrotriazol-1-yl-H-phosphonate 6 a (Supporting Information, Figure 2 ), which was detected by 31 P NMR spectroscopy ( δ =13.1 and 14.1 ppm, J PH =652 and 656 Hz, respectively).…”

Section: Resultsmentioning

confidence: 99%

Chemical Synthesis of Burkholderia Lipid A Modified with Glycosyl Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐β‐L‐arabinose and Its Immunomodulatory Potential

Hollaus

Ittig

Hofinger

et al. 2015

Chemistry A European J

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Modification of the Lipid A phosphates by positively charged appendages is a part of the survival strategy of numerous opportunistic Gram-negative bacteria. The phosphate groups of the cystic fibrosis adapted Burkholderia Lipid A are abundantly esterified by 4-amino-4-deoxy-β-l-arabinose (β-l-Ara4N), which imposes resistance to antibiotic treatment and contributes to bacterial virulence. To establish structural features accounting for the unique pro-inflammatory activity of Burkholderia LPS we have synthesised Lipid A substituted by β-l-Ara4N at the anomeric phosphate and its Ara4N-free counterpart. The double glycosyl phosphodiester was assembled by triazolyl-tris-(pyrrolidinyl)phosphonium-assisted coupling of the β-l-Ara4N H-phosphonate to α-lactol of β(1→6) diglucosamine, pentaacylated with (R)-(3)-acyloxyacyl- and Alloc-protected (R)-(3)-hydroxyacyl residues. The intermediate 1,1′-glycosyl-H-phosphonate diester was oxidised in anhydrous conditions to provide, after total deprotection, β-l-Ara4N-substituted Burkholderia Lipid A. The β-l-Ara4N modification significantly enhanced the pro-inflammatory innate immune signaling of otherwise non-endotoxic Burkholderia Lipid A.

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Section: Resultsmentioning

confidence: 99%

Chemical Synthesis of Burkholderia Lipid A Modified with Glycosyl Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐β‐L‐arabinose and Its Immunomodulatory Potential

Hollaus

Ittig

Hofinger

et al. 2015

Chemistry A European J

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“…Coupling of H ‐phosphonate 5 was performed with chlorotripyrrolidinophosphonium hexafluorophosphate (PyTP) followed by conversion into the silylated phosphite triester with bis(trimethylsilyl)acetamide (BSA) and subsequent oxidation with camphorsulfonic acid (CSO) . This approach, however, produced the diester derivative 19 only in a poor yield.…”

Section: Resultsmentioning

confidence: 99%

Synthetic Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐l‐arabinose Derivatives Demonstrate that ArnT is an Inverting Aminoarabinosyl Transferase

et al. 2019

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Abstract4‐Amino‐4‐deoxy‐l‐arabinopyranose (Ara4N) residues have been linked to antibiotic resistance due to reduction of the negative charge in the lipid A and core regions of the bacterial lipopolysaccharide (LPS). To study the enzymatic transfer of Ara4N onto lipid A, which is catalysed by the ArnT transferase, we chemically synthesised a series of anomeric phosphodiester‐linked lipid Ara4N derivatives containing linear aliphatic chains as well as E‐ and Z‐configured monoterpene units. Coupling reactions were based on sugar‐derived H‐phosphonates, followed by oxidation and global deprotection. The enzymatic Ara4N transfer was performed in vitro with crude membranes from a deep‐rough mutant from Escherichia coli as acceptor. Product formation was detected by TLC and LC‐ESI‐QTOF mass spectrometry. Out of seven analogues tested, only the α‐neryl derivative was accepted by the Burkholderia cenocepacia ArnT protein, leading to substitution of the Kdo2‐lipid A acceptor and thus affording evidence that ArnT is an inverting glycosyl transferase that requires the Z‐configured double bond next to the anomeric phosphate moiety. This approach provides an easily accessible donor substrate for biochemical studies relating to modifications of bacterial LPS that modulate antibiotic resistance and immune recognition.

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“…Indeed, the subsequent key P V coupling reaction of 30 with 34 under the agency of TMBSC and MNO afforded a mixture of the fully protected target compound me‐ADPR ( 32 ) and its monodemethylated analogue in a combined yield of 60 %. Previously, Wada and co‐workers had shown that phosphonium reagents are selective activators and effective agents for the condensation of methylphosphonates with alcohols . Using 3‐nitro‐1,2,4‐triazol‐1‐yl‐tris(pyrrolidin‐1‐yl)phosphonium hexafluorophosphate (PyNTP) as the condensation agent further improved the yield of protected me‐ADPR ( 32 ) to 84 % (Figure S5).…”

Section: Figurementioning

confidence: 99%

Combined Phosphoramidite‐Phosphodiester Reagents for the Synthesis of Methylene Bisphosphonates

et al. 2017

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A new class of phosphanylmethylphosphonate reagents has been developed to enable the controlled synthesis of methylene bisphosphonate mono‐ and diesters. Condensation of such reagents with an alcohol of choice through azole‐mediated phosphoramidite chemistry followed by in situ oxidation provides orthogonally protected methylene bisphosphonate tetraesters. Global deprotection of the tetraester leads to terminal methylene bisphosphonates. Alternatively, selective deprotection at the terminal phosphonate followed by a condensation between the acquired methylene bisphosphonate triester and a second alcohol leads to methylene bisphosphonates diesters.

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1,3-Dimethyl-2-(3-nitro-1,2,4-triazol-1-yl)-2-pyrrolidin-1-yl-1,3,2-diazaphospholidinium hexafluorophosphate (MNTP): a powerful condensing reagent for phosphate and phosphonate esters

Abstract: A novel phosphonium-type condensing reagent,

Cited by 33 publications

References 34 publications

Chemical Synthesis of Burkholderia Lipid A Modified with Glycosyl Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐β‐L‐arabinose and Its Immunomodulatory Potential

Chemical Synthesis of Burkholderia Lipid A Modified with Glycosyl Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐β‐L‐arabinose and Its Immunomodulatory Potential

Synthetic Phosphodiester‐Linked 4‐Amino‐4‐deoxy‐l‐arabinose Derivatives Demonstrate that ArnT is an Inverting Aminoarabinosyl Transferase

Combined Phosphoramidite‐Phosphodiester Reagents for the Synthesis of Methylene Bisphosphonates

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