Solvolytic Studies on Methylnorbornyl Systems: Investigations on the Synthesis of 2-Exo-methyl-6-norbomylideneacetic Acid

1979 ◽  
Vol 34 (3) ◽  
pp. 481-487
Author(s):  
J. Radhakrishnan
Keyword(s):  
Methyl Acrylate ◽  
Diethyl Malonate ◽  
Propargyl Alcohol ◽  
Ethyl Bromoacetate ◽  
Alkylation Reactions

Abstract3-Nortricyclyl bromide (11) was transformed in four steps to norbornan-3,6-dione (10). Methyl 4-hydroxy-2-butynoate (19) was prepared from propargyl alcohol and its alkylation reactions with 3-methylcyclopentanone investigated. Methyl 4,4,5-triethoxycarbonylpentanoate (22) was obtained by the sequential alkylation of diethyl malonate with ethyl bromoacetate and methyl acrylate, and its base catalysed cyclization studied. Cyclopentadiene was converted to 2-exo-methylnorbornan-6-one (17) in eleven steps.

Synthetic Utility of 1-Hydroxycarbazole-2-carbaldehydes - Syntheses of Furo-, Oxazino- and Pyranocarbazoles

2007 ◽  
Vol 72 (11) ◽  
pp. 1579-1590 ◽  
Author(s):  
Arputharaj E. Martin ◽  
Karnam J. Rajendra Prasad
Keyword(s):  
Ethyl Acetoacetate ◽  
Diethyl Malonate ◽  
Product Formation ◽  
Phenacyl Bromide ◽  
Ethyl Bromoacetate ◽  
Synthetic Utility

Reaction of 1-hydroxycarbazole-2-carbaldehydes 1 with phenacyl bromide yielded 2-benzoyl-10H-furo[2,3-a]carbazoles 2, whereas the reaction with ethyl bromoacetate yielded 1-oxo-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazole-4-carbaldehyde (4). The reaction of 1 with ethyl acetoacetate and also with diethyl malonate yielded the pyranocarbazoles 6 and 7, respectively. All the products were characterized by spectral and analytical means. Plausible mechanisms of product formation are proposed.

Alkylation reactions of propargyl alcohol; improved routes to prostaglandin α-side chain precursors

Tetrahedron ◽  
1986 ◽  
Vol 42 (21) ◽  
pp. 5849-5856 ◽  
Author(s):  
Guy Casy ◽  
Mark Furber ◽  
Kevan A. Richardson ◽  
G.Richard Stephenson ◽  
Richard J.K. Taylor
Keyword(s):  
Propargyl Alcohol ◽  
Side Chain ◽  
Alkylation Reactions

ChemInform Abstract: Alkylation Reactions of Propargyl Alcohol; Improved Routes to Prostaglandin α-Side Chain Precursors.

ChemInform ◽  
1987 ◽  
Vol 18 (14) ◽  
Author(s):  
G. CASY ◽  
M. FURBER ◽  
K. A. RICHARDSON ◽  
G. R. STEPHENSON ◽  
R. J. K. TAYLOR
Keyword(s):  
Propargyl Alcohol ◽  
Side Chain ◽  
Alkylation Reactions

Biomedical Materials to Repair Retinal Detachments

1985 ◽  
Vol 55 ◽  
Author(s):  
Miguel F. Refojo
Keyword(s):  
Retinal Detachment ◽  
Silicone Rubber ◽  
Methyl Acrylate ◽  
Silicone Oil ◽  
Vitreous Body ◽  
Light Sensitivity ◽  
Scleral Buckling ◽  
Intraocular Injection ◽  
Other Substances

ABSTRACTImplants are essential for the repair of retinal detachments. The implant buckles the wall of the eye and apposes the detached retina with the choroid, thus restoring light sensitivity to the retina. The scleral buckling also relieves traction on the retina from a shrinking vitreous body. The implant materials most commonly used are solid silicone rubber and silicone sponges, but both types have some disadvantages. A poly(hydroxyethyl acrylate-co-methyl acrylate) hydrogel implant with improved properties of softness and antibiotic absorption is also available for retinal detachment surgery. Proliferative vitreoretinopathy involves various conditions of retinal detachment complicated by vitreous fibrosis, which, after vitrectomy, may be treated with intraocular injection of fluids that support the retina against the choroid. For conditions requiring a long-term implant, silicone oil although controversial is the material of choice. Many other substances have been investigated but none better has yet been found.

Copper Catalyzed sp3 C-H α-Acetylation

2019 ◽  
Author(s):  
Otome Okoromoba ◽  
Eun Sil Jang ◽  
Claire McMullin ◽  
Thomas Cundari ◽  
Timothy H. Warren
Keyword(s):  
Natural Products ◽  
Dft Studies ◽  
Alkyl Radicals ◽  
Important Chemical ◽  
Alkyl Electrophiles ◽  
Synthetic Intermediates ◽  
Alkylation Reactions

<p>α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp<sup>3</sup> C-H α-acetylation of sp<sup>3</sup> C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH<sub>2</sub>R at RT with <sup>t</sup>BuOO<sup>t</sup>Bu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [Cu<sup>II</sup>](CH<sub>2</sub>C(O)Ar) that capture alkyl radicals R• to give R-CH<sub>2</sub>C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH<sub>2</sub>CH<sub>2</sub>C(O)Ar.</p>

Copper Catalyzed sp3 C-H α-Acetylation

2019 ◽  
Author(s):  
Otome Okoromoba ◽  
Eun Sil Jang ◽  
Claire McMullin ◽  
Thomas Cundari ◽  
Timothy H. Warren
Keyword(s):  
Natural Products ◽  
Dft Studies ◽  
Alkyl Radicals ◽  
Important Chemical ◽  
Alkyl Electrophiles ◽  
Synthetic Intermediates ◽  
Alkylation Reactions

<p>α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp<sup>3</sup> C-H α-acetylation of sp<sup>3</sup> C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH<sub>2</sub>R at RT with <sup>t</sup>BuOO<sup>t</sup>Bu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [Cu<sup>II</sup>](CH<sub>2</sub>C(O)Ar) that capture alkyl radicals R• to give R-CH<sub>2</sub>C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH<sub>2</sub>CH<sub>2</sub>C(O)Ar.</p>

An Anthrone-Based Kv7.2/7.3 Channel Blocker with Improved Properties for the Investigation of Psychiatric and Neurodegenerative Disorders

2019 ◽  
Author(s):  
Jacob Porter ◽  
Oscar Vivas-Rodriguez ◽  
C. David Weaver ◽  
Eamonn Dickson ◽  
Abdulmohsen Alsafran ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Neurodegenerative Disorders ◽  
Channel Blocker ◽  
Optimal Combination ◽  
Channel Blockers ◽  
Enolate Alkylation ◽  
Cyp Inhibition ◽  
Alkylation Reactions ◽  
Metabolic Instability

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC<sub>50</sub>= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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