scholarly journals The McKenna reaction – avoiding side reactions in phosphonate deprotection

2020 ◽  
Vol 16 ◽  
pp. 1436-1446 ◽  
Author(s):  
Katarzyna Justyna ◽  
Joanna Małolepsza ◽  
Damian Kusy ◽  
Waldemar Maniukiewicz ◽  
Katarzyna M Błażewska
Keyword(s):  
Side Reactions ◽  
Phosphonic Acids ◽  
Full Extent ◽  
Popular Method ◽  
Phosphonate Esters

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.

scholarly journals A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mattia Forchetta ◽  
Valeria Conte ◽  
Giulia Fiorani ◽  
Pierluca Galloni ◽  
Federica Sabuzi
Keyword(s):  
Metal Oxides ◽  
Phosphonic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Phosphonic Acids ◽  
Sustainable Improvement ◽  
Phosphonate Esters ◽  
First Time ◽  
Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

Pyrimidine Acyclic Nucleotide Analogues with Aromatic Substituents in C-5 Position

2007 ◽  
Vol 72 (7) ◽  
pp. 927-951 ◽  
Author(s):  
Marcela Krečmerová ◽  
Antonín Holý ◽  
Milena Masojídková
Keyword(s):  
Antiviral Activity ◽  
Cell Cultures ◽  
Inhibitory Activity ◽  
Thymidine Phosphorylase ◽  
Sodium Hydride ◽  
Phosphonic Acids ◽  
Nucleotide Analogues ◽  
Varicella Zoster ◽  
Subsequent Hydrolysis ◽  
Phosphonate Esters

NH2-protected 5-phenylcytosine and its derivatives 2a-2d were treated with (2S)-2-[(trityloxy)methyl]oxirane (3) followed by etherification with diisopropyl [(tosyloxy)methyl]phosphonate (5) in the presence of sodium hydride. The intermediary phosphonate esters 6 were debenzoylated and subsequently transformed to free phosphonic acids, i.e. (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenylcytosine (5-phenyl-HPMPC) derivatives (8a-8d) by the action of bromotrimethylsilane and subsequent hydrolysis. Deamination of these compounds with 3-methylbutyl nitrite afforded corresponding (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenyluracil (5-phenyl-HPMPU) derivatives (9a-9d). R-Enantiomers 14 and 15 were prepared analogously starting from (2R)-2-[(trityloxy)methyl]oxirane. 5-Benzyl-, 5-[(1-naphthyl)methyl]- and 5-[(2-naphthyl)methyl]HPMPU (24a-24c) and -HPMPC (25a-25c) were synthesized from appropriate 5-arylmethyl-4-methoxypyrimidin-2(1H)-ones similarly as described for 5-phenyl derivatives. Antiviral activity was found for (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenyluracil (9a) (HSV-1 and HSV-2) and (R)-1-[3-hydroxy2-(phosphonomethoxy)propyl]-5-phenylcytosine (14) (cytomegalovirus and varicella-zoster virus), both tested in cell cultures. Some of the 5-phenyluracil derivatives possessed inhibitory activity against thymidine phosphorylase from SD-lymphoma.

Preparation of C-5 Substituted Cidofovir Derivatives

2006 ◽  
Vol 71 (4) ◽  
pp. 579-594 ◽  
Author(s):  
Marcela Krečmerová ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Antiviral Activity ◽  
Primary Amines ◽  
Sonogashira Coupling ◽  
Phosphonic Acids ◽  
Phosphonate Esters ◽  
Base Moiety

1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, cidofovir) was modified by substitution on the base moiety in positions C-5 and N4. Key intermediates of these syntheses, diisopropyl esters of (S)-1-[2-(phosphonomethoxy)-3-(triphenylmethoxy)propyl]-5-alkylcytosines (6 and 7) prepared from 5-alkyl-4-methoxypyrimidin-2(1H)-ones were transformed to the corresponding 5-substituted cytosine or N4-alkylcytosine derivatives by the action of ammonia or primary amines, respectively. These fully protected phosphonate esters gave by treatment with bromotrimethylsilane followed by hydrolysis free phosphonic acids: 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]-5-methylcytosine (5-methyl-HPMPC, 10), 5-ethyl-1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (5-ethyl-HPMPC, 11) and a series of 5-ethyl-HPMPC analogues 17-21 bearing various substituents in N4 position (cyclopropyl, cyclopentyl, 2-hydroxyethyl, allyl, 2-(dimethylamino)ethyl). 5-Ethynyl-1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (5-ethynyl-HPMPC, 26) was prepared from 5-iodocytosine derivative 23 using Sonogashira coupling with (trimethylsilyl)acetylene, CuI and [PdCl2(Ph3P)2]. None of the prepared compounds exhibited antiviral activity in vitro.

Infrared Spectra of Cyclic Phosphonate Esters

1966 ◽  
Vol 20 (1) ◽  
pp. 47-51 ◽  
Author(s):  
T. H. Siddall ◽  
R. N. Wilhite
Keyword(s):  
Infrared Spectra ◽  
Organophosphorus Compounds ◽  
Phosphonic Acids ◽  
Phosphonate Esters

A number of medium to strong bands were found in the infrared spectra of heterocyclic esters of 1,3 and 1,4 glycols with phosphonic acids. A set of such bands appears to be characteristic of the esters of a given glycol with all the phosphonic acids. Some of the bands of each set were also observed for esters of phenylphosphoric acid. Such sets of bands do not appear to have been reported for other organophosphorus compounds.

Preservation of Plant Cell Surfaces For Scanning Electron Microscopy

1973 ◽  
Vol 31 ◽  
pp. 472-473
Author(s):  
Linda M. Sicko ◽  
Thomas E. Jensen
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Critical Point ◽  
Filter Paper ◽  
Freeze Drying ◽  
Cell Surfaces ◽  
Air Drying ◽  
Popular Method ◽  
Critical Point Drying ◽  
Scanning Electron

The use of critical point drying is rapidly becoming a popular method of preparing biological samples for scanning electron microscopy. The procedure is rapid, and produces consistent results with a variety of samples. The preservation of surface details is much greater than that of air drying, and the procedure is less complicated than that of freeze drying. This paper will present results comparing conventional air-drying of plant specimens to critical point drying, both of fixed and unfixed material. The preservation of delicate structures which are easily damaged in processing and the use of filter paper as a vehicle for drying will be discussed.

Aldehyde gold clusters for molecular labeling

1995 ◽  
Vol 53 ◽  
pp. 858-859
Author(s):  
James F. Hainfeld ◽  
Frederic R. Furuya
Keyword(s):  
Covalent Bond ◽  
Aldehyde Group ◽  
Gold Clusters ◽  
Side Reactions ◽  
Amino Groups ◽  
Sodium Cyanoborohydride ◽  
Schiff’S Base ◽  
Protein Molecules ◽  
Hydroxysuccinimide Esters ◽  
Primary Amino

Glutaraldehyde is a useful tissue and molecular fixing reagents. The aldehyde moiety reacts mainly with primary amino groups to form a Schiff's base, which is reversible but reasonably stable at pH 7; a stable covalent bond may be formed by reduction with, e.g., sodium cyanoborohydride (Fig. 1). The bifunctional glutaraldehyde, (CHO-(CH2)3-CHO), successfully stabilizes protein molecules due to generally plentiful amines on their surface; bovine serum albumin has 60; 59 lysines + 1 α-amino. With some enzymes, catalytic activity after fixing is preserved; with respect to antigens, glutaraldehyde treatment can compromise their recognition by antibodies in some cases. Complicating the chemistry somewhat are the reported side reactions, where glutaraldehyde reacts with other amino acid side chains, cysteine, histidine, and tyrosine. It has also been reported that glutaraldehyde can polymerize in aqueous solution. Newer crosslinkers have been found that are more specific for the amino group, such as the N-hydroxysuccinimide esters, and are commonly preferred for forming conjugates. However, most of these linkers hydrolyze in solution, so that the activity is lost over several hours, whereas the aldehyde group is stable in solution, and may have an advantage of overall efficiency.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Energetic Control of Redox-Active Polymers Towards Safe Organic Bioelectronic Materials

2019 ◽  
Author(s):  
Alexander Giovannitti ◽  
Reem B. Rashid ◽  
Quentin Thiburce ◽  
Bryan D. Paulsen ◽  
Camila Cendra ◽  
...  
Keyword(s):  
Molecular Oxygen ◽  
Organic Semiconductors ◽  
Side Reaction ◽  
Semiconducting Polymers ◽  
Side Reactions ◽  
Redox Active ◽  
Donor Acceptor ◽  
Electrochemical Devices ◽  
Biological Environment ◽  
Device Operation

<p>Avoiding faradaic side reactions during the operation of electrochemical devices is important to enhance the device stability, to achieve low power consumption, and to prevent the formation of reactive side‑products. This is particularly important for bioelectronic devices which are designed to operate in biological systems. While redox‑active materials based on conducting and semiconducting polymers represent an exciting class of materials for bioelectronic devices, they are susceptible to electrochemical side‑reactions with molecular oxygen during device operation. We show that this electrochemical side reaction yields hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), a reactive side‑product, which may be harmful to the local biological environment and may also accelerate device degradation. We report a design strategy for the development of redox-active organic semiconductors based on donor-acceptor copolymers that prevent the formation of H<sub>2</sub>O<sub>2</sub> during device operation. This study elucidates the previously overlooked side-reactions between redox-active conjugated polymers and molecular oxygen in electrochemical devices for bioelectronics, which is critical for the operation of electrolyte‑gated devices in application-relevant environments.</p>

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