Substituent effects on the reaction mode between 2-hydroxybenzyl alcohol derivatives and MEM chloride: synthesis and mechanistic aspects of seven- and ten-membered benzo-fused O,O-acetals

Saniger, Estrella; Díaz‐Gavilán, Mónica; Delgado, Beatriz; Choquesillo, Duane; González‐Pérez, Josefa María; Aiello, Stefania; Gallo, Miguel Á.; Espinosa, Antonio; Campos, Joaquı́n M.

doi:10.1016/j.tet.2004.09.077

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…The general methods were the same as those previously described. , One-dimensional NOE-difference experiments were performed by irradiation for 4 s in a series of eight scans with alternating on- and off-resonance. The irradiating power was set low to achieve selectivity.…”

Section: Methodsmentioning

confidence: 99%

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

et al. 2006

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(RS)-1-(2-Nitrobenzenesulfonyl)- and (RS)-1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepines are better substrates than 1-acyl-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 degrees C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1" position, while the attachment of the uracil fragment is through N-3" or N-1" of the cyclic or acyclic products, respectively. The causes that influence the course of the reactions are analyzed and discussed. Examination of the (1)H NMR spectra revealed the presence of a single form for the secondary amine 11 and of two conformers for the tertiary sulfonamides 7a,b, 9a,b, and 10b and for the amides 7d and 13, with the following distribution: 7a, 59/41; 7b, 53/47; 9a, 52/48; 9b, 59/41; 10b, 56/44; 7d, 50/50; 13, 80/20. On increasing the temperature, the (1)H NMR spectrum (DMSO-d(6)) of 7b showed coalescence at 110 degrees C. The torsional barrier determined [DeltaG(c)++ value of 19.0 +/- 0.2 kcal.mol(-1) (79.1 +/- 1.0 kJ.mol(-1))] proved to be the highest ever observed for sulfonamide moieties.

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Section: Methodsmentioning

confidence: 99%

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

et al. 2006

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“…[9] The unprotected hydroxy group was then alkylated with bromoacetaldehyde dimethyl acetal, [9] and substitution of the OMe group by the 5-FU moiety with concomitant deprotection of the phenolic OH group was accomplished in a single-step, one-pot reaction (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

“…A solution of SnCl 4 /CH 2 Cl 2 (1.0 m, 1.9 mmol) was added dropwise with stirring under argon at room temperature to a suspension of 13 a,d,e, [9] 14, [7] (Z)-15, [7] 16, 24 b, [8] and 24 c [8] (1.6 mmol), 5-fluorouracil (5-FU, 1.8 mmol), containing trimethylchlorosilane (TCS, 1.6 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (HMDS, 1.6 mmol) in dry acetonitrile (10 mL mmol À1 ). After stirring for 24 h, the reaction was quenched by the addition of a concentrated aqueous solution of Na 2 CO 3 .…”

Section: Final Compoundsmentioning

confidence: 99%

Antiproliferative Activity, Cell‐Cycle Dysregulation, and Cellular Differentiation: Salicyl‐ and Catechol‐Derived Acyclic 5‐Fluorouracil O,N‐Acetals against Breast Cancer Cells

et al. 2007

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Herein we report the preparation and biological activity of three compounds with the general formula 1-[2-(5-substituted-2-hydroxybenzyloxy)-1-methoxyethyl]-5-fluorouracil. A catechol-derived compound such as 1-[3-(2-hydroxyphenoxy)-1-methoxypropyl]-5-fluorouracil and two salicyl-derived compounds such as (Z)-1-[4-(2-hydroxyphenyl)-1-methoxybut-3-enyl]-5-fluorouracil [(Z)-11] and its dihydrogenated derivative 1-[4-(2-hydroxyphenyl)-1-methoxybutyl]-5-fluorouracil were prepared to complete the set of six O,N-acetals. The most active compound against the MCF-7 breast cancer cell line was (Z)-11: IC(50)=9.40+/-0.64 microM. Differentiated breast cancer cells generate fat deposits in the cytoplasm. MCF-7 cells treated with (Z)-11 underwent an increase in lipid content relative to control cells after three days of treatment. Our results suggest that there may be significant potential advantages in the use of this new differentiating agent for the treatment of breast cancer.

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1,4-Dioxepanes, 1,4-Oxathiepanes, and 1,4-Dithiepanes

Frauenrath

Flock

Murugan³

et al. 2008

Comprehensive Heterocyclic Chemistry III

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Substituent effects on the reaction mode between 2-hydroxybenzyl alcohol derivatives and MEM chloride: synthesis and mechanistic aspects of seven- and ten-membered benzo-fused O,O-acetals

Cited by 5 publications

References 18 publications

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

Antiproliferative Activity, Cell‐Cycle Dysregulation, and Cellular Differentiation: Salicyl‐ and Catechol‐Derived Acyclic 5‐Fluorouracil O,N‐Acetals against Breast Cancer Cells

1,4-Dioxepanes, 1,4-Oxathiepanes, and 1,4-Dithiepanes

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