Synthesis of isomeric series of aryltetrahydrobenz‐isoxazoles and arylcyclopentisoxazoles

Abstract

Four series of potential PAF‐antagonists in which the isoxazole nucleus is condensed with a polyhydrogenated five‐ or six‐carbon ring were prepared. The synthesis of the compounds 3‐aryl‐4,5,6,7‐tetrahydrobenz[c]isoxazoles 1, 3‐arylcyclopent[c]isoxazoles 2, 3‐aryl‐4,5,6,7‐tetrahydrobenz[d]isoxazoles 3, and 3‐arylcyclopent[d]isoxazoles 4, required an extensive optimization and comparison of the methods available in the literature.

Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells

“…Crucial steps in these syntheses were Huisgen-type 1,3-dipolar cycloaddition reactions of norbornene (for the closer analogues) and other alkenes with nitrile oxides ( Jawalekar et al, 2011 ; Huisgen, 1963 ) and related 1,3-dipoles. Related aromatic isoxazole analogues were prepared via cycloaddition of nitrile oxides with ketone enolates ( Vitale and Scilimati, 2013 ) or enamines ( Fos et al, 1992 ). General synthesis strategies for these modifications are shown in Figure 1A .…”

“…Dehydration with sodium carbonate resulted in aromatic analogues of SN-2. 5-Morpholinoisoxazolines (EVP-82, EVP-85) were generated in a similar manner from the ketones via enamines ( Fos et al, 1992 ; Kuehne et al, 1964 ). Other 5-membered ring heterocycles like isoxazolidines (EVP-94) ( Cerri et al, 1974 ), isomeric isoxazoles (EVP-103) ( Fos et al, 1992 ), triazolines (EVP-199), pyrazolines (EVP-110) ( Wulfman et al, 1988 ), and isothiazoles (EVP-109) ( Akiba et al, 1985 ) were obtained by following established procedures of heterocyclic chemistry.…”

Mode of Action of 4-Hydroxyphenylpyruvate Dioxygenase Inhibition by Triketone-type Inhibitors

“…Next, compound 2 , as shown in Scheme , was generated by reacting 1-morpholinecyclohexene (prepared by dehydration of cyclohexanone with morpholine) with 2-nitrobenzoyl chloride under basic conditions followed by refluxing in an aqueous acid for 5 h …”

“…Next, compound 2, as shown in Scheme 3, was generated by reacting 1-morpholinecyclohexene (prepared by dehydration of cyclohexanone with morpholine) 10 with 2-nitrobenzoyl chloride under basic conditions followed by refluxing in an aqueous acid for 5 h. 11 The ratio of enol/keto isomers, determined by 1 H NMR spectra, was found to be 97/3. Unfortunately but not surprisingly, reacting 2-nitrobenzyl bromide with cyclohexane-1,3-dione in triethylamine in CH 2 Cl 2 gave the major undesired vinyl ether 12 and minor desired compound 8 in the ratio of 2/1.…”

Regioselectivity Switch: Gold(I)-Catalyzed Oxidative Rearrangement of Propargyl Alcohols to 1,3-Diketones

“…Yield: 69 mg as a mixture of a keto and an enol forms (keto/enol = 53:47 by 1 H NMR), 79%; 1 H NMR (300 MHz, CDCl 3 , keto/enol = 53:47) δ = 14.74 (s, 1 H, enol), 7.98 (d, 1 H, J = 8.7 Hz, keto and enol), 7.77 (d, 1 H, J = 8.7 Hz, keto and enol), 6.95 (d, 2 H, J = 8.7 Hz, keto and enol),4.20 (t, 1 H, J = 7.8 Hz, keto), 3.87 (s, 3 H, keto), 3.86 (s, 3 H, enol), 2.90–1.88 (m, 6 H, keto and enol). 3c is known …”