An Efficient Process for the Synthesis of trans-2,3-Disubstituted-2,3-dihydro-4H-1-benzopyran-4-ones (Chroman-4-ones)

Draper, Richard W.; Hu, Bin; Iyer, Radha V.; Li, Xun; Lu, Yuelie; Rahman, Muhammad Arif; Vater, Eugene J.

doi:10.1016/s0040-4020(00)00101-0

Cited by 20 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The third step was a Knoevenagel reaction of bis-THP ether 6 with 4-hydroxybenzaldehyde, in the presence of piperidine in refluxing benzene which gave quantitatively a mixture of chromanones 7 (3:1 trans/cis ratio) and chalcones 8 (4:1 Z/E ratio) at a 2:1 molar ratio. The crude intermediates 7 and 8 were then alkylated with several 1-(2-chloroethyl)dialkylamines hydrochloride 9 in the presence of Cs 2 CO 3 in refluxing acetone -water, to yield the chromanones 10 contaminated with chalcones 11 at 40 -90% yields [46]. In the case of the amine 9b, the Knoevenagel reaction gave the chromatographed chromanones 10b (, 5:1 trans/cis ratio), which contain about 15% of Zchalcone 11b, in a 65% yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and structure–activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution

Gauthier

Cloutier

Dory

et al. 2005

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

EM-652 (acolbifene) analogs have been synthesized as selective estrogen receptor modulators. Substitution on the nitrogen atom of these 2H-1-benzopyran derivatives has been studied for its influence on antiestrogenic activity. Binding to the rat estrogen receptor, inhibition of estradiol-stimulated proliferation of T-47D breast cancer cells, as well as antiuterotrophic and uterotrophic activities in ovariectomized mice have been evaluated. 2H-1-Benzopyran 1b (EM-343, racemic form of EM-652), which contains a piperidine ring, shows the best pharmacological profile; RBA = 380, IC50 value = 0.110 nM (in T-47D cells), as well as 63% and 84% antiuterotrophic inhibitions at the 7.5 and 75 nmol doses, respectively.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and structure–activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution

Gauthier

Cloutier

Dory

et al. 2005

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…3 Various derivatives of this system are also inhibitors of SIRT2, an enzyme involved in agerelated neurodegenerative disorders. 4 Finally, 4-chromanones have been used in the synthesis of somatostatin analogues which are currently under investigation as a possible treatment for osteoporosis 5 as well as certain stomach tumors. 6 We have previously reported synthetic routes to tetrahydronaphthalenes, 7 tetrahydroisoquinolines 8 and tetrahydroquinolines 9 using relatively mild catalysts for ring closure via a Friedel-Crafts alkylation.…”

mentioning

confidence: 99%

“…11 Since then, the amine-catalyzed condensation of o-hydroxyacetophenones with aliphatic ketones and aldehydes has proven to be a more versatile approach. [3][4][5][6][12][13][14] Further accounts have detailed the use of stoichiometric mercury(II) on aryl propargyl ethers, 15 the addition of cuprates to chromones, 16 the treatment of phenols and 3,3-dimethylacrylic acid with excess phosphorus oxychloride/zinc chloride, 17,18 the reaction of carboxylic acids with o-(trimethylsilyl)aryl triflates promoted by cesium fluoride 19 and a one-pot, base-mediated photo-Fries-oxa-Michael reaction. 20 The current project originated from efforts to extend the Friedel-Crafts ring closure of phenyl 3,3-dimethylacrylate (1a, X = H) to other phenol-derived acrylate esters.…”

mentioning

confidence: 99%

Bismuth(III) triflate catalyzed tandem esterification–Fries–oxa-Michael route to 4-chromanones

Meraz

Gnanasekaran

Thing

et al. 2016

Tetrahedron Letters

View full text Add to dashboard Cite

An efficient tandem reaction approach is described to prepare 4-chromanones from electron-rich phenols and 3,3-dimethylacrylic acid or trans-crotonic acid in boiling toluene using 20 mol% bismuth(III) triflate as the catalyst. The reaction is also successful from the corresponding aryl esters of each of these acids under the same conditions. The procedure is convenient to perform, and 25-90% yields of products are realized following chromatography. A range of substrates is included (14 substrates for each acid) to help define the scope of the process. Additional experiments are reported, which confirm that the sequence of events involves (1) esterification, (2) Fries rearrangement and (3) oxa-Michael ring closure.

show abstract

“…Furthermore, we could start directly with an advanced intermediate of the acolbifene commercial process synthesis, the diprotected trans-chromanone 15. 20 The low cost of trideuterated methylating reagents with high enrichment was also considered.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronides

Sancéau

Larouche

Caron

et al. 2007

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Acolbifene (EM-652 Á HCl, SCH 57068 Á HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4 0 -glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2 H-labelled derivatives 4-6 were synthesised for use as preclinical and clinical standards for LC-MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at À108C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C 2 H 3 MgI followed by dehydration with C

show abstract

An Efficient Process for the Synthesis of trans-2,3-Disubstituted-2,3-dihydro-4H-1-benzopyran-4-ones (Chroman-4-ones)

Cited by 20 publications

References 15 publications

Synthesis and structure–activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution

Synthesis and structure–activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution

Bismuth(III) triflate catalyzed tandem esterification–Fries–oxa-Michael route to 4-chromanones

Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronides

Contact Info

Product

Resources

About