How To Get the Most Out of Two Phosphorus Chemistries. Studies on H-Phosphonates

Stawiński, Jacek; Kraszewski, Adam

doi:10.1021/ar010049p

Cited by 175 publications

(90 citation statements)

References 74 publications

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“…It is important to know that the share of each tautomer is different when the connected groups to the phosphorus atom are changed. In the reported studies, it has been shown that electron-donating alkyl and aryl groups stabilize the phosphine oxide tautomer while electron-withdrawing substituents, such as trifluoromethyl, stabilize the phosphinous acid structure [9,10].…”

Section: Introductionmentioning

confidence: 99%

The Substituent Effect on the Energy Profiles of Inter and Intramolecular Proton Transfers between Phosphine Oxide‐Phosphinous Acid Tautomers

Tavakol

Keshavarzipour

2016

Heteroatom Chemistry

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This report presents the energy details related to mechanistic pathways of tautomeric interconversion between phosphinous acids and phosphine oxides with different substituents using DFT, MP2 and CCSD (T) calculations. Four mechanisms consisting of simple, dimer, water-assisted (with 1, 2, and 3 molecules of water), and methanol-assisted have been considered. In the most cases and all pathways, the halogen-containing phosphorus compounds preferred phosphinous acid tautomer and the other structures preferred phosphine oxide tautomers. In simple tautomerism, the high-energy barriers showed the impossible pathway for this interconversion and halogen substituents had higher rate constants. In dimeric mechanism, the relative stability of phosphine oxide tautomer was increased and the tautomeric processes via this mechanism were found to have the higher rates versus the simple mechanism. In the solvent-assisted mechanism, except one structure, the relative stability of phosphinous acids was increased in comparison with the simple or dimer cases. Moreover, activation energies showed the great enhancements in the rates of these interconversions in the direct presence of the solvent.

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Section: Introductionmentioning

confidence: 99%

The Substituent Effect on the Energy Profiles of Inter and Intramolecular Proton Transfers between Phosphine Oxide‐Phosphinous Acid Tautomers

Tavakol

Keshavarzipour

2016

Heteroatom Chemistry

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“…1 Due to known separation problems, many recent efforts in the Mitsunobu reaction research have been directed toward modifying triphenylphosphine and azodicarboxylate reagents 3,4 to facilitate purification procedures, or to develop special, usually chromatographyfree, separation strategies. 4,5 As part of our program in developing synthetic methods for biologically important phosphates and their analogues based on H-phosphonate chemistry, 6,7 we became interested in the Mitsunobu reaction for two reasons. Firstly, it permits a condensation to be carried out under mild, virtually neutral conditions, and secondly, it involves activation of a hydroxyl function of an alcohol, rather than conversion of a pronucleophile into a reactive species.…”

Section: Introductionmentioning

confidence: 99%

Synthetic studies on nucleoside 5'-H-phosphonate monoesters under Mitsunobu reaction conditions

Lavén¹,

Stawiński²

2008

Arkivoc

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“…In principle, this methodology can be readily extended to other molecules which have a free hydroxyl group. 15,28 …”

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confidence: 99%

New Silybin Scaffold for Chemical Diversification: Synthesis of Novel 23-Phosphodiester Silybin Conjugates

Zarrelli

Romanucci

Greca

et al. 2012

Synlett

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Silybin is the major component (ca. 30%) of the silymarin complex extracted from the seeds of Silybum marianum, with multiple biological activities operating at various cell levels. As an ongoing effort toward the exploitation of natural products as scaffolds for chemical diversification at readily accessible positions, we present here an efficient synthetic procedure to obtain new 23-phosphodiester silybin conjugates with different labels. A key point in our approach is the new 3,5,7,20-tetra-O-acetylsilybin-23-phosphoramidite, useful for a variety of derivatizations following a reliable and well-known chemistry. The feasibility of the procedure has been demonstrated by preparing new 23-silybin conjugates, exploiting standard phosphoramidite chemistry.Key words: natural products, flavonolignans, silybin, phosphorylation, drugs Flavonoids and flavonolignans are widely distributed among various citrus plants and are frequently found in the human diet. They may act as enzyme inhibitors, freeradical scavengers, antitumor agents, antibacterial agents, anti-inflammatory agents, and antioxidants. [1][2][3] Silybin (Figure 1) is the major component (ca. 30%) of the silymarin complex extracted from the seeds of Silybum marianum consisting of two diastereomers A and B in a ratio of approximately 1:1. Silybin is a natural compound with multiple biological activities operating at various cell levels most of them related to its radical-scavenging activity. Along with the beneficial activities resulting from the antioxidant and radical-scavenging properties, 3,4 silybin has recently received attention due to its anticancer and chemopreventive actions, 5,6 as well as hypocholesterolemic, cardioprotective, and neuroprotective activities. 3,7 In vivo applications of silybin are rather hampered by its very low bioavailability. In an attempt to improve its biological properties and facilitate in vivo applications of silybin, only limited structural modifications have been proposed 3,[8][9][10][11][12] and the available analogues are still unsatisfactory. Therefore new synthetic approaches for selectively modifying silybin are of interest. As a part of our continuing research effort towards the synthesis of new natural product analogues, 13,14 we present here the preliminary results of a efficient synthetic procedure to obtain new 23-phosphodiester silybin conjugates with different labels. The introduction of a phosphate group may bring pharmaceutical and pharmacokinetic benefits. 15 Conjugation is usually considered as an efficient route in drug discovery to improve the biological properties of a large number of drugs and can improve the bioavailability and delivery as well as the biological activity. We chose to start from the new 23-phosphoramidite building block 3 (Scheme 1) which could be transformed into a series of conjugates using a solution-phase parallel array protocol, exploiting standard and reliable phosphoramidite chemistry. 15 We initially converted silybin (1) into its 23-ODMT ether by a reaction with DMT...

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How To Get the Most Out of Two Phosphorus Chemistries. Studies on H-Phosphonates

Cited by 175 publications

References 74 publications

The Substituent Effect on the Energy Profiles of Inter and Intramolecular Proton Transfers between Phosphine Oxide‐Phosphinous Acid Tautomers

The Substituent Effect on the Energy Profiles of Inter and Intramolecular Proton Transfers between Phosphine Oxide‐Phosphinous Acid Tautomers

Synthetic studies on nucleoside 5'-H-phosphonate monoesters under Mitsunobu reaction conditions

New Silybin Scaffold for Chemical Diversification: Synthesis of Novel 23-Phosphodiester Silybin Conjugates

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