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Isobaric chemical labeling is a widely used strategy for high-throughput quantitative proteomics based on mass spectrometry. However, commercially available reagents have high costs in applications as well as the sensitivity limitations for detection of the trace protein samples. Previously, we developed a 2-plex isobaric labeling strategy based on phosphorus chemistry for ultrasensitive proteome quantification with high accuracy. In this work, 6-plex tandem phosphorus tags (TPT) were developed with 3-fold increase in the multiplexing quantitative capacity compared to the 2-plex isobaric phosphorus reagents introduced previously. High isotope enrichment of 18 O labeling was incorporated into the phosphoryl group with three exchangeable oxygen atoms by using commercially available H 2 18 O. The combinational incorporations of 18 O atom in reporter ions and balance group set up the low-cost foundation for development of multiplex TPT reagents. The novel 6-plex TPT reagents could produce phosphoramidate as unique reporter ions with approximately 1 Da mass difference and thus enable 6-plex quantitative analysis in high-resolution ESI-MS/MS analysis. Using HeLa cell tryptic peptides, we concluded that 6-plex TPT reagents could facilitate large-scale accurate quantitative proteomics with very high labeling efficiency.

The Ser-His dipeptide is the shortest active peptide. This dipeptide not only hydrolyzes proteins and DNA but also catalyzes the formation of peptides and phosphodiester bonds. As a potential candidate for the prototype of modern hydrolase, Ser-His has attracted increasing attention. To explore if Ser-His could be obtained efficiently in the prebiotic condition, we investigated the reactions of N-DIPP-Ser with His or other amino acids in an aqueous system. We observed that N-DIPP-Ser incubated with His can form Ser-His more efficiently than with other amino acids. A synergistic effect involving the two side chains of Ser and His is presumed to be the critical factor for the selectivity of this specific peptide formation.

A series of phosphorus-substituted germanium(II) complexes, L(1)GeR [L(1) = CH{(CMe)(2,6-(i)Pr2C6H3N)}2; 2, R = PPh2; 4, R = OPPh2; 5a, R = OP(O)Ph2; 5b, R = OP(O) (O(n)Bu)2; 6a, R = OP(S)Ph2; 6b, R = OP(S)(OEt)2], were synthesized through the direct activation of various organic phosphorus compounds by N-heterocyclic ylide-like germylene 1. These compounds were characterized by IR and NMR spectroscopy, and 4, 5a, 6a, and 6b were further investigated by X-ray crystallography. Interestingly, the reaction of 1 with Ph2P(O)H produced the tricoordinated phosphorus(III) species L(1)GeOPPh2 (4) rather than the expected isomeric product L(1)GeP(O)Ph2. The reaction of 1 with dialkylthiophosphoric acid and diphenylthiophosphinic acid resulted in the products 6a and 6b containing the P═S double bond rather than the P═O double bond.

Rationale: α-Amino phosphonates with intrinsic biological activities have been used in a wide variety of applications. Because of the widespread existence of natural organophosphorus compounds containing P-C bonds such as the α-amino phosphonates, it is important to investigate the gas-phase chemistry of P-C bonds in order to determine their basic properties, which might provide some insights into their biosynthesis and catalytic cleavage., Methods: Twenty α-amino phosphonates were successfully synthesized and their fragmentation behavior was systematically investigated using in-solution deuterium labeling in combination with high-resolution Fourier transform ion cyclotron resonance (FTICR) electrospray ionization tandem mass spectrometry., Results: The fragmentation pathways of twenty α-amino phosphonates with different chemical structures were systematically studied. In general, P-C bonds could be easily cleaved via a novel intramolecular hydrogen atom migration from the amino group to the phosphoryl group through a five-membered-ring intermediate in the gas phase. A possible mechanism of the rearrangement of α-amino phosphonates is proposed., Conclusions: An interesting intramolecular hydrogen atom migration between the amino and phosphoryl groups was observed with cleavage of the P-C bond in the molecule through a five-membered-ring intermediate. This characteristic fragmentation pathway not only provides some insights into the basic chemistry of compounds with P-C bonds, but could also have some applications in the structural determination of the α-amino phosphonate analogues., (Copyright © 2014 John Wiley & Sons, Ltd.)

A new method for copper-catalyzed P-C bond formation through reaction of phosphorus nucleophiles with diaryliodonium salts at room temperature is described. Most target products are obtained with this method in high yields within a short reaction time of 10 min. It can be easily adapted to large-scale preparations. When unsymmetrical iodonium salts are employed, nucleophilic substitution occurs preferentially on the sterically hindered aromatic ring or the more electron-deficient ring.

In this paper, we describe the development of a novel stable isotope N-phosphorylation labeling (SIPL) strategy for peptide de novo sequencing and protein quantification based on organic phosphorus chemistry. The labeling reaction could be performed easily and completed within 40 min in a one-pot reaction without additional cleanup procedures. It was found that N-phosphorylation labeling reagents were activated in situ to form labeling intermediates with high reactivity targeting on N-terminus and ε-amino groups of lysine under mild reaction conditions. The introduction of N-terminal-labeled phosphoryl group not only improved the ionization efficiency of peptides and increased the protein sequence coverage for peptide mass fingerprints but also greatly enhanced the intensities of b ions, suppressed the internal fragments, and reduced the complexity of the tandem mass spectrometry (MS/MS) fragmentation patterns of peptides. By using nano liquid chromatography chip/time-of-flight mass spectrometry (nano LC-chip/TOF MS) for the protein quantification, the obtained results showed excellent correlation of the measured ratios to theoretical ratios with relative errors ranging from 0.5% to 6.7% and relative standard deviation of less than 10.6%, indicating that the developed method was reproducible and precise. The isotope effect was negligible because of the deuterium atoms were placed adjacent to the neutral phosphoryl group with high electrophilicity and moderately small size. Moreover, the SIPL approach used inexpensive reagents and was amenable to samples from various sources, including cell culture, biological fluids, and tissues. The method development based on organic phosphorus chemistry offered a new approach for quantitative proteomics by using novel stable isotope labeling reagents.

A mild and efficient method was developed for the copper-catalyzed additions of H-phosphonate diesters to boronic acids under the copper catalyst system Cu(2)O/1,10-phenanthroline. To the best of our knowledge this finding is the first example of a copper-catalyzed synthesis of aryl phosphonates from arylboronic acids and H-phosphonate dialkyl esters., (© 2011 American Chemical Society)

Synthesis of valuable compounds directly from small and simple molecules is an area of great interest in chemical research. However, the preparation of most organophosphorus compounds from white phosphorus currently relies on inefficient, stepwise procedures that result in significant environmental pollution and poor atom economy. We herein describe a novel and high-yielding route to generate various phosphorothioates with diverse substituents from white phosphorus, disulfides, and alcohols in a single reaction step. This innovative three-component coupling reaction utilizes basic industrial raw materials and offers several advantages, including operational simplicity, mild reaction conditions, a broad substrate scope, and high product selectivity. [ABSTRACT FROM AUTHOR]

Metal phosphates are important catalysts and materials in synthesis chemistry. Herein, we describe the synthesis and characterization of phosphate‐catecholate chelated Nd(III), Zr(IV) and Al(III) chlorides (2–5). These species are achieved via ethyl chloride elimination reaction of oxophosphoranes with corresponding metal chlorides. The product 2–5 represent a new serial of monometallic and bimetallic phosphate‐catecholate chelated metal complexes stabilized by both P−O and catecholate‐O donors. These findings pave the way for future explorations of such species in catalysis. [ABSTRACT FROM AUTHOR]

The reaction of the stannyl phosphaketene (Nacnac)SnPCO 1 (Nacnac = CH{(CMe)(2,6-iPr2C6H3N)}2) with B(C6F5)3 produced the 1,4-addition product of (Nacnac)SnPCO(B(C6F5)3). However, the corresponding reactions in the presence of dimethyl maleate, diisopropyl fumarate or diethyl-but-2-ynedioate gave [2+2] addition yielding four-membered phosphacycles, ((Nacnac)Sn(MeO2C))CHPC(OB(C6F5)3)CH(CO2Me), [(C6F5)3B)PC(OSn)C(CO2Me)CH(CO2Me)]2, (Nacnac)Sn(iPrO2C)CC(OAl(C6F5)3)P[CH(CO2iPr)CH2(CO2iPr)]CH(CO2iPr), and (Nacnac)SnP (EtO2CCC(CO2Et))CO(B(C6F5)3), respectively. In contrast, the corresponding reaction of phenylacetylene gave the FLP-addition product (Nacnac)SnOC(P)C(Ph)CH(B(C6F5)3). Collectively, this reactivity demonstrates that the stannyl phosphaketene 1 can act as a synthon for P-analogues of β-lactam derivatives. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A transition‐metal‐free one‐pot direct synthesis of tetrathiophosphates (R1S)2P(S)SR2 from white phosphorus (P4), through intermediate sodium alkyltetrathiophosphates (R1S)2P(S)SNa, is presented. In the presence of NaSH, various disulfides such as diaryl disulfidbges and dialkyl disulfides are easily coupled with P4 to give sodium alkyltetrathiophosphates (R1S)2P(S)SNa in almost quantitative yield, which react with alkyl halides in one pot to generate (R1S)2P(S)SR2. Furthermore, S‐(2‐cyanoethyl)‐substituted tetrathiophosphates (R1S)2P(S)SCH2CH2CN are successfully designed as a kind of tetrathiophosphorylation reagent to react with diaryl iodonium salts involving deprotection‐dealkylation process. [ABSTRACT FROM AUTHOR]

The development of practical and mild catalytic methods for the direct transformation of white phosphorus into value-added organophosphorus compounds, without the hazardous chlorination step, represents an important advancement in the field of organic synthesis. The first organic-dye-catalyzed radical cascade alkylation of white phosphorus with unactivated alkyl iodides was developed, which selectively afforded structurally diverse dialkylphosphines in moderate to good yields. This practical reaction operates under metal-free conditions and exhibits good functional group tolerance and high phosphorus conversion. [ABSTRACT FROM AUTHOR]

Correction for 'Metal-free visible-light-induced phosphorylation of unactivated alkyl iodides with white phosphorus as the P-atom source' by Fushan Chen et al., Green Chem., 2023, 25, 6629–6634, https://doi.org/10.1039/D3GC01579C. [ABSTRACT FROM AUTHOR]

Developing practical and mild strategies for the direct functionalization of white phosphorus (P4) without chlorination is an appealing but formidable challenge. To this end, we report a breakthrough in the preparation of structurally diverse dialkylphosphines and trialkylphosphines that rely on the successive generation of carbon‐centered radicals from N‐hydroxyphthalimide (NHPI) esters and the controllable alkylation of the P4 molecule under transition‐metal‐ and photocatalyst‐free conditions. To facilitate separation and prevent product losses during purification, the corresponding oxidation products dialkylphosphine oxides (DAPOs) and trialkylphosphine oxides (TAPOs) were isolated. This photoinduced phosphorylation reaction features one‐pot operation, high product selectivity, and tolerates a broad range of alkyl NHPI esters, including derivatives of complex natural products and pharmaceuticals. Further diversified transformation of DAPOs to construct P−F, P−C, P−N, and P−O bonds was also demonstrated. [ABSTRACT FROM AUTHOR]

Dialkyl phosphites (DAPIs), traditionally prepared from hazardous and corrosive PCl3, are the fundamental reactive starting materials used in organophosphorus chemistry. Here, a KBr‐mediated synthesis of DAPIs involving P4, alcohols and water is presented. With the use of silica gel as the catalyst, oxone as the safe oxidant, industrially important (EtO)2P(O)H, (i‐PrO)2P(O)H and (MeO)2P(O)H are prepared in 70–90% yields. Furthermore, rare metal extractant bis(2‐ethylhexyl) phosphate (D2EHPA) is obtained in 73% yield. The reaction is characterized by a complete conversion of white phosphorus. Moreover, this method can be easily adapted to large‐scale preparation. [ABSTRACT FROM AUTHOR]

Functionalization of white phosphorus with disulfides, amines and KOH to phosphoramidodithioates containing both P−N, P−S and P=O bonds via a four‐component reaction is presented. It proceeds with high yields and provides an attractive approach for the construction of valuable N−P(O)−S motif using a one‐step strategy. The advantages of this newly developed process include a clean reaction profile, complete conversion of white phosphorus, transition metal‐free and halogen‐free environmentally benign system, and large‐scale synthetic application. Besides, phosphoramidodithioates can also be utilized to construct P−C, P−O and P=S bonds with the appropriate reagents. [ABSTRACT FROM AUTHOR]

The first general and high-yielding synthesis of mixed phosphorotrithioates (R1S)2P(O)SR2 involving white phosphorus, disulfides, and alkyl halides is presented, which provides the shortest and environmentally benign method to synthesize these compounds of practical importance. Only one method for the formation of (R1S)2P(O)SR2 from elemental phosphorus has been developed. Here, with the use of KOH as a base and DMSO–toluene as a solvent, various disulfides couple readily with white phosphorus to give O-potassium S,S-dialkylphosphorotrithioates (R1S)2P(S)OK in almost quantitative yields, which react with alkyl halides to form (R1S)2P(O)SR2 in high yields. The reaction is characterized by the complete conversion of white phosphorus. Moreover, this method can be easily adapted to large-scale preparation. Our mechanistic data suggest that the attack of RSK on S,S,S-trialkyl phosphorotrithioates and subsequent C–S bond cleavage, the Michaelis–Arbuzov-like dealkylation, are the key steps in the formation of (R1S)2P(S)OK. [ABSTRACT FROM AUTHOR]

White phosphorus (P4) is still the major commercial P-atom source for the production of organophosphorus compounds. Conventionally, C–S–P bonds were constructed from environmentally questionable P(O)X directly or indirectly. From the green chemistry point of view, formation of C–S–P bonds from inorganic molecule P4 in an easy-to-operate and atom-economical way is essential because it will avoid the hazardous chlorination process. Only five methods for the formation of C–S–P bonds from P4 have been developed over the past 70 years. Here, the first general and high-yielding synthesis of P(SR)3 and P(O)(SR)3 involving P4 and thiols is presented. With the use of KOH or K2CO3 as a base and DMSO–toluene as a solvent, both arythiols and alkylthiols are tolerant in this transformation. The reaction is characterized by a complete conversion of white phosphorus. This operationally simple and environmentally sound reaction shows a broad scope of substrates and good functional group tolerance. Moreover, this method can be easily adapted to large-scale preparation. [ABSTRACT FROM AUTHOR]

The first Pd‐catalyzed domino Heck/phosphorylation of N‐(2‐iodophenyl)acrylamides with secondary phosphine oxides has been developed. The use of PdCl2 as a catalyst, 1,4‐bis(diphenylphosphino)butane as a ligand, K2CO3 as a base, various N‐(2‐iodophenyl)acrylamide derivatives are tolerant in this transformation, affording 3‐phosphinomethyl 3,3‐disubstituted oxindole products in good to excellent yields. This transformation offers a straightforward route to the formation of the new C−C and P−C bonds, oxindole ring in one step. Moreover, this method can be easily adapted to large‐scale preparation. [ABSTRACT FROM AUTHOR]

Correction for 'Stannyl phosphaketene as a synthon for phosphorus analogues of β-lactams' by Yong-an Luo et al., Chem. Commun., 2023, https://doi.org/10.1039/d3cc03117a. [ABSTRACT FROM AUTHOR]

The novel phosphate derivatives of phosphaphenanthrene with high-density phosphorus were synthesized and used as flame retardant additives for Li-ion batteries. The structures of compounds were characterized by H NMR, C NMR, P NMR, FT-IR, and HR-MS. The excellent thermal stability of compounds was ascertained by thermogravimetric analysis and differential scanning calorimetry. The compounds were added to conventional electrolytes as flame retardant additives and evaluated their ionic conductivity, electrochemical stability, self-extinguishing properties, and combustion performance. The results showed that the compound containing higher phosphorus content has efficient flame retardant properties. [ABSTRACT FROM AUTHOR]

Two novel cyclotetraphosphazene derivatives were synthesized by the reaction of octachlorocyclotetraphosphazene with the potassium salt of 4-hydroxybenzaldehyde, and subsequent reduction of aldehyde groups to alcohol groups using sodium borohydride. The bromination reaction was carried out using PBr3 to give N4P4(OC6H4-p-CH2Br)8 (4). This compound was employed in reaction with imidazole or morpholine to produce eight-armed, star-branched title compounds. The target compounds were characterized by 1H, 31P, and 13C NMR as well as IR and ESI-MS. The Cu complex of 5a was effective in oxidative cleavage reactions. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT[image omitted] [ABSTRACT FROM AUTHOR]

Abstract: The electrospray ionization tandem mass spectra (ESI-MS n ) of the sodium adducts of N-diisopropyloxyphosphoryl (DIPP) dipeptide methyl esters containing unnatural amino acids, such as DIPP-β-Ala-Phe-OMe and DIPP-γ-amino butyric acid-Phe-OMe, were studied. An unusual rearrangement reaction with a carbonyl oxygen migration through a six- or seven-membered ring tetracoordinate phosphorus transition state was observed. In addition, ESI-MS n of DIPP-l/d-α-Ala-Phe-OMe was also investigated. The transition state of their rearrangement was a five-membered ring pentacoordinate phosphorus transition state. It was the spatial configuration of phosphorus atom and the strong affinity between phosphorus and oxygen atoms that induced the carbonyl oxygen migration through different cyclic transition state. The results imply that the carbonyl oxygen migration in the ESI-MS/MS of dipeptide methyl esters was not dependent on the chain length of the amino acid at the N-terminus. [Copyright &y& Elsevier]

A novel, efficient method for the synthesis of spirophosphoranes containing a pentacoordinated P–C bond has been developed by P-alkylation reaction between pentacoordinated hydrospirophosphorane and halohydrocarbon. A series of new spirophosphoranes were synthesized, and the relative phosphorus configurations were presumed by 1H NMR NOESY or coupling constants experiment. Furthermore, the stereochemical mechanism of the pentacoordinated P-alkylation reaction was proposed by the verified experiment and 31P NMR tracing experiment. Image 1 • The spirophosphoranes containing a pentacoordinated P–C bond have been synthesized by P-alkylation reaction. • The relative pentacoordinated phosphorus configurations were presumed by 1H NMR NOESY and coupling constants. • The stereochemical mechanism of the P-alkylation reaction was proposed. [ABSTRACT FROM AUTHOR]

A diagram is presented which shows the chemical formulas for organo-phosphorus compounds, copper, and oxidation of alkynyl acids with H-phosphine oxides.