Potential Inhibitors of Phosphoenolpyruvate Carboxylase. II. Phosphonic Acid Substrate Analogs Derived From Reaction of Trialkyl Phosphites With Halomethacrylates

1989 ◽  
Vol 42 (2) ◽  
pp. 301 ◽  
Author(s):  
HG Mcfadden ◽  
RLN Harris ◽  
CLD Jenkins
Keyword(s):  
Double Bond ◽  
Nucleophilic Substitution ◽  
Phosphonic Acid ◽  
Phosphoenolpyruvate Carboxylase ◽  
Reaction Conditions ◽  
Pep Carboxylase ◽  
Substrate Analogs ◽  
Trialkyl Phosphites ◽  
Potential Inhibitors ◽  
Acid Substrate

Analogues of phosphoenolpyruvate (PEP), the substrate of PEP carboxylase , were synthesized as potential inhibitors of the enzyme. Esterified analogue precursors were obtained by nucleophilic substitution of various halomethacrylate derivatives with trialkyl phosphites. Substitution of the halomethacrylates can occur either α to the leaving halogen or in the γ position with subsequent allylic shift of the double bond. The course of the reaction was influenced both by reaction conditions and the nature of the substituents on the reactants. The phosphonomethacrylates obtained were hydrolysed to PEP analogues that were found to be moderate to good inhibitors of PEP carboxylase. Phosphonomethacrylic acid derivatives bearing two halogen substituents in the γ position were found to be the most potent inhibitors of this enzyme.

Potential Inhibitors of Phosphoenolpyruvate (PEP) Carboxylase: Phosphonic Acid Substrate-Analogs Derived From Stobbe-Type Condensations of Ethyl 3-(Diethoxyphosphinoyl)propanoate

1987 ◽  
Vol 40 (10) ◽  
pp. 1619 ◽  
Author(s):  
HG Mcfadden ◽  
RLN Harris ◽  
CLD Jenkins
Keyword(s):  
Phosphonic Acid ◽  
Acid Group ◽  
Pep Carboxylase ◽  
Substrate Analogs ◽  
Alkyl Groups ◽  
Potential Inhibitors ◽  
Mild Hydrolysis ◽  
Hydrolysis Of ◽  
Acid Substrate ◽  
Partial Esters

Phosphonic acid analogues of 2-(dihydroxyphosphinoy1oxy)propenoic acid (PEP), the substrate of PEP carboxylase, were prepared and tested as inhibitors of the enzyme. The required triacids were obtained by mild hydrolysis of the partial esters prepared by Stobbe-like condensation of aryl and alkyl carbonyl compounds with ethyl 3-(diethoxyphosphinoyl)propanoate. Condensations with aldehydes gave predominantly (9-propenoates while reactions with ketones gave mixtures of (E)- and (Z)-isomers and also, in some cases, products with the double bond rearranged to the &position. Although compounds tested were inhibitory, none was as effective as previously reported phosphate PEP analogues. Results indicate that the presence of a methyl group cis to the carboxylic acid group enhances inhibitory activity but that trans alkyl groups decrease inhibitor effectiveness.

One-pot Synthesis of Pyrazolone Sulfones by Iodine-catalyzed Sulfenylation of Pyrazolones with Aryl Sulfonyl Hydrazides Followed by Oxidation in Water

2018 ◽  
Vol 15 (3) ◽  
pp. 380-387
Author(s):  
Xia Zhao ◽  
Xiaoyu Lu ◽  
Lipeng Zhang ◽  
Tianjiao Li ◽  
Kui Lu
Keyword(s):  
Double Bond ◽  
Efficient Method ◽  
Room Temperature ◽  
Sulfonyl Chloride ◽  
Antibacterial Activities ◽  
Oxidation Reactions ◽  
Reaction Conditions ◽  
One Pot ◽  
X Ray ◽  
Amide Form

Aim and Objective: Pyrazolone sulfones have been reported to exhibit herbicidal and antibacterial activities. In spite of their good bioactivities, only a few methods have been developed to prepare pyrazolone sulfones. However, the substrate scope of these methods is limited. Moreover, the direct sulfonylation of pyrazolone by aryl sulfonyl chloride failed to give pyrazolone sulfones. Thus, developing a more efficient method to synthesize pyrazolone sulfones is very important. Materials and Method: Pyrazolone, aryl sulphonyl hydrazide, iodine, p-toluenesulphonic acid and water were mixed in a sealed tube, which was heated to 100°C for 12 hours. The mixture was cooled to 0°C and m-CPBA was added in batches. The mixture was allowed to stir for 30 min at room temperature. The crude product was purified by silica gel column chromatography to afford sulfuryl pyrazolone. Results: In all cases, the sulfenylation products were formed smoothly under the optimized reaction conditions, and were then oxidized to the corresponding sulfones in good yields by 3-chloroperoxybenzoic acid (m-CPBA) in water. Single crystal X-ray analysis of pyrazolone sulfone 4aa showed that the major tautomer of pyrazolone sulfones was the amide form instead of the enol form observed for pyrazolone thioethers. Moreover, the C=N double bond isomerized to form an α,β-unsaturated C=C double bond. Conclusion: An efficient method to synthesize pyrazolone thioethers by iodine-catalyzed sulfenylation of pyrazolones with aryl sulfonyl hydrazides in water was developed. Moreover, this method was employed to synthesize pyrazolone sulfones in one-pot by subsequent sulfenylation and oxidation reactions.

Some Analogs of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid: Synthesis and Antiinflammatory Activity

1995 ◽  
Vol 60 (6) ◽  
pp. 1026-1033 ◽  
Author(s):  
Miroslav Kuchař ◽  
Václav Vosátka ◽  
Marie Poppová ◽  
Eva Knězová ◽  
Vladimíra Panajotovová ◽  
...  
Keyword(s):  
Double Bond ◽  
Antiinflammatory Activity ◽  
Acid Synthesis ◽  
Reaction Conditions ◽  
Methyl Group ◽  
Oxobutanoic Acid

Analogs of 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (I, flobufen), containing a double bond (II, IV, V, VII, VIII) or a methyl group in position 3 (VI) were prepared. Their antiinflammatory activity was evaluated and compared with that of flobufen. None of the mentioned analogs reached the activity of the standard. Isomerization of the unsaturated derivatives is connected with a shift of the double bond, Z-E transformation or lactonization. Reaction conditions and spectra of the compounds prepared are described.

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.

Double bond isomerization of ethyl linoleate and vegetable oils to conjugated derivatives over an LDH supported ruthenium catalyst

RSC Advances ◽  
2015 ◽  
Vol 5 (45) ◽  
pp. 36075-36082 ◽  
Author(s):  
Sivashunmugam Sankaranarayanan ◽  
Gobi Selvam ◽  
Kannan Srinivasan
Keyword(s):  
Double Bond ◽  
Vegetable Oils ◽  
Ethyl Linoleate ◽  
Ruthenium Catalyst ◽  
Reaction Conditions ◽  
Double Bond Isomerization

Isomerization of ethyl linoleate and vegetable oils to conjugated derivatives is achieved over an MgAl-LDH supported ruthenium catalyst under mild reaction conditions.

Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach

2018 ◽  
Vol 16 (37) ◽  
pp. 8267-8272 ◽  
Author(s):  
S. N. Murthy Boddapati ◽  
Chandra Mohan Kurmarayuni ◽  
Baby Ramana Mutchu ◽  
Ramana Tamminana ◽  
Hari Babu Bollikolla
Keyword(s):  
Nucleophilic Substitution ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Reaction Conditions ◽  
Moderate Reaction ◽  
Cross Coupling Reactions ◽  
Novel Approach

Substituted 2-aminophenyl benzothiazoles have been constructed from thiourea via copper-catalyzed desulfurization/nucleophilic substitution followed by domino intra- and intermolecular C–N cross-coupling reactions under moderate reaction conditions.

scholarly journals A new and efficient protocol for the synthesis of the key intermediate of Palbociclib

2019 ◽  
Vol 43 (1-2) ◽  
pp. 14-19
Author(s):  
Shuting Li ◽  
Wanfeng Yang ◽  
Min Ji ◽  
Jin Cai ◽  
Junqing Chen
Keyword(s):  
Nucleophilic Substitution ◽  
Heck Reaction ◽  
Ring Closure ◽  
Efficient Synthesis ◽  
Reaction Conditions ◽  
Synthetic Strategy

A new and efficient synthesis of 6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)-pyrido[2,3-d]pyrimidin-7(8H)-one, a key intermediate of Palbociclib, starting from thiouracil was described. This protocol involved methylation, nucleophilic substitution, bromination, nucleophilic substitution, Heck reaction, ring closure, oxidation, and bromination to afford a key intermediate of Palbociclib with approximately 35% overall yield. The advantages of this developed synthetic strategy included improved overall yield, inexpensive starting materials, and readily controllable and cleaner reaction conditions.

An Example of Ketone Olefination via Praseodymium-Mediated Barbier Reaction in the Presence of Diethyl Phosphite

Synlett ◽  
2019 ◽  
Vol 30 (12) ◽  
pp. 1437-1441
Author(s):  
Xu yan Cao ◽  
Fei Huang ◽  
Songlin Zhang
Keyword(s):  
Double Bond ◽  
Bond Formation ◽  
Point Of View ◽  
Diethyl Phosphite ◽  
Reaction Conditions ◽  
One Pot ◽  
Type Reaction ◽  
Mild Conditions ◽  
Allyl Halides ◽  
Barbier Reaction

The first example of carbon double-bond formation via praseodymium-mediated Barbier type reaction of ketones and allyl halides in the presence of diethyl phosphite is reported. The reaction is highly α-regioselective and conveniently carried out under mild conditions in a one-pot fashion. From a synthetic point of view, a series of conjugated alkenes were obtained in moderate to good yields in this one-pot reaction with practical reaction conditions.

Neodymium-Promoted Highly Selective Carbon–Carbon Double Bond Formation of Ketones with Allyl Halides in the Presence of Diethyl Phosphite

Synthesis ◽  
2020 ◽  
Vol 52 (22) ◽  
pp. 3446-3451
Author(s):  
Songlin Zhang ◽  
Dengbing Xie ◽  
Yiqiong Wang ◽  
Bo Yang
Keyword(s):  
Double Bond ◽  
Bond Formation ◽  
Point Of View ◽  
Diethyl Phosphite ◽  
Reaction Conditions ◽  
One Pot ◽  
Mild Conditions ◽  
Carbon Double Bond ◽  
Allyl Halides ◽  
First Time

The carbon–carbon double bond formation via neodymium-mediated Barbier-type reaction of ketones and allyl halides in the presence of diethyl phosphite is reported for the first time. The reaction is highly α-regioselective and was conveniently carried out under mild conditions in a one-pot fashion. From a synthetic point of view, a series of conjugated alkenes were obtained in moderate to good yields in this one-pot reaction with feasible reaction conditions.

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