The Synthesis of Phosphonic and Phosphinic Acids and their Derivatives: Non‐Functionalized Acids

Edmundson, R. S.

doi:10.1002/9780470682531.pat0062

Cited by 6 publications

(8 citation statements)

References 398 publications

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“…The equilibrium constant for these compounds usually strongly favors the tetracoordinated tautomer (108, 109). Nevertheless, phosphonous acids and phosphonites are known to carry out both electrophilic and nucleophilic reactions (109, 110). The most straightforward mechanism for the methyl transfer to phosphorus would therefore be attack of a tervalent form of AcDM-PTT onto the methyl group of MeCbl (Figure 7A).…”

Section: Phosphinothricinmentioning

confidence: 99%

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

Metcalf

Donk

2009

Annu. Rev. Biochem.

301

299

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Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lies behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin, and the clinical candidate for treatment of malaria FR900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations and a wealth of new biochemistry has been revealed through their study. These studies have also suggested new strategies for natural product discovery. metcalf@uiuc.edu, vddonk@uiuc.edu. Summary Points •Phosphonates and phosphinates function by mimicking phosphate esters or anhydrides or carboxylate groups in enzyme substrates. As such, a large number of enzymes can be potential targets of this class of compounds.• The number of unprecedented reactions involved in the biosynthesis of fosfomycin, phosphinothricin, and FR900098 is an indication of the wealth of novel biochemistry used in the biosynthesis of this class of compounds.• Phosphoenolpyruvate (PEP) mutase catalyzes the C-P bond-forming step in all naturally occurring phosphonates for which the gene clusters are currently known. Hence, degenerate primers for PEPM can be used for the discovery of new phosphonate encoding gene clusters and hence new natural products.• Given the current commercial use of phosphonates and phosphinates in medicine and agriculture, discovery of new naturally occurring compounds beyond the twenty or so currently known structures may provide an important untapped source of new products for human use. Future issues• Based on the large number of metabolic processes that can be targeted with phosphonates, numerous phosphonate and phosphinate containing natural products likely remain to be discovered. Future studies will confirm or refute this hypothesis.• The fundamentally new radical-SAM strategy for methylation of unactivated carbon centers must be confirmed or disproven by in vitro studies.• The molecular logic that dictates epoxidation by HppE and C-C bond cleavage in HEPD is not understood and requires further investigation. Fine-tuning the activities of these enzymes may result in useful catalysts for synthetic purposes.• What is the cellular target of dehydrophos?• What alternative strategies are used in Nature to install a C-P bond that do not rely on the PEP mutase-like reaction?

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Section: Phosphinothricinmentioning

confidence: 99%

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

Metcalf

Donk

2009

Annu. Rev. Biochem.

301

299

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“…These couplings start from N,Ndialkylphosphoramide dichlorides (R 2 NPCl 2 ) or N,N-dialkylphosphoramic dichlorides [R 2 NP(O)Cl 2 ] or alternatively involve the reaction of aryldiazonium fluoroborates with PCl 3 in the presence of a catalyst (CuBr). [4] These methods generally give suboptimal yields, often lead to mixtures, and also generate significant amounts of waste salts.…”

Section: Introductionmentioning

confidence: 99%

A Direct Catalytic Synthesis of Sodium Diarylphosphinates and Their Corresponding Acids from Sodium Phosphinate

et al. 2016

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“…The corresponding phosphinic acids 3 are the key intermediates in this synthesis and they form, after activation to phosphinic halides, the desired phosphinates 1 via a nucleophilic substitution reaction (Scheme 1 , path A). 9 Of course, first the organophosphinic acids 3 need to be prepared using, for example, a hydrophosphonation reaction of alkenes with hypophosphorous acid 4 , 10 a reaction between dialkyl hydrogen phosphites 5 and organometallic reagents followed by oxidation, 10 etc. 11 12 A generic strategy towards phosphinates 1 is not available yet.…”

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“…11 12 A generic strategy towards phosphinates 1 is not available yet. 10 13 The used synthetic pathway is therefore dependent on the structure of the desired phosphinate 1 .…”

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confidence: 99%

“…Phosphorus trichloride ( 6 ) can be substituted with an excess of alcohol in the presence of base and the resulting phosphite ester 7 can be subjected to an Michaelis–Arbuzov reaction with a haloalkane to form a phosphonate 2 (Scheme 1 , path B). 1 10 13 However, the latter reaction requires high temperatures and only primary haloalkanes react readily. Under certain conditions, secondary haloalkanes might also react, but tertiary haloalkanes and haloarenes are unreactive in the Michaelis–Arbuzov reaction.…”

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Selective Substitution of POCl3 with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates

2018

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The selectivity of the substitution reaction of phosphoryl chloride with organometallic reagents was investigated using NMR spectroscopy. This led to the discovery that the selectivity of the substitution reaction can be tuned by choosing a proper organometallic reagent. A phosphinate could be obtained by using a Grignard reagent whereas an organozinc reagent provided a phosphonate. Based on these results, one-pot synthetic methods for the preparation of phosphinates and phosphonates using commercially available starting materials were developed. Both methods allow the synthesis of a broad range of either phosphinate or phosphonate derivatives in a straightforward and general procedure. Moreover, using these one-pot procedures, mixed systems substituted with different alkyl/aryl groups can be prepared.

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The Synthesis of Phosphonic and Phosphinic Acids and their Derivatives: Non‐Functionalized Acids

Abstract: Introduction The Formation of P  C ( sp 3 ) Bonds. Syntheses of Alkyl, Cycloalkyl and Aralkyl Phosphonic and Phosphinic Acids The Formation of P  C ( sp 2 ) Bonds. Syntheses of Alkenyl and Alkadienyl Phosph… Show more

Cited by 6 publications

References 398 publications

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

A Direct Catalytic Synthesis of Sodium Diarylphosphinates and Their Corresponding Acids from Sodium Phosphinate

Selective Substitution of POCl3 with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates

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