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Synlett 2007(6): 0921-0924  
DOI: 10.1055/s-2007-973886
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of Apoptotic Inducers, 2,2-Diphenyl-1,3,2-oxazaborolidin-5-ones, Under Alkaline Conditions

Benjamín Velasco-Bejarano*a,b, José Trujillo-Ferraraa, René Mirandab
a Departamento de Bioquímica Médica, Escuela Superior de Medicina-IPN, México D.F., 11340, México
b Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán-UNAM, Estado de México, 54740, México
Fax: +52(55)56232056; e-Mail: qfbbevebe@gmail.com;
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Publication History

Received 13 July 2006
Publication Date:
26 March 2007 (online)

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Abstract

An efficient and high-yielding procedure has been developed for the synthesis of a set of fifteen 2,2-diphenyl-1,3,2-oxazaborolidin-5-ones, through the reaction of the corresponding α-amino acid with diphenyl borinic acid under alkaline conditions (pH 7.5-8). It is of note that these compounds showed potent cytotoxic activity on K-562 and HCT-15 cell lines.

Key words

α-amino acids - diphenyloxazaborolidinones - boron complexes - apoptosis - diphenylborinic acid

    References and Notes

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16

Typical procedure (Table 1, entry 1, 3a): Glycine (0.5g, 6.6 mmol) was dissolved in H2O (3 mL) and the pH was ad-justed to 8 with NaOH (5%, 2 mL). A solution of diphenyl-borinic acid was prepared from 2-aminoethyl-diphenyl-borinate (1.59 g, 6.6 mmol) as described in the literature.14 The solutions were mixed together and heated at reflux for 4 h. The solvent was evaporated slowly and the product was filtered and washed with cold H2O and n-hexane, yielding 1.49 g of 3a (6.26 mmol, 94%).

17

Cytotoxicity in K-562 and HCT-15 cell lines, using the sulforhodamine B assay: Skehan P., Storeng R., Scudiero D., Monks A., McMahon J., Vistica D., Warren J. T., Bokesh H., Kenney S., Boyd M.R.; J. Natl. Cancer Inst.; 1990, 82: 1107; 24 h after treatment, the treated and control cell cultures were fixed with ice-cold 10% CCl3COOH for 30 min. The 96-well plates were washed in H2O and then sulforhodamine (SRB, 100 µL, 0.4%) dissolved in AcOH (1%) was added to each well and left for 15 min. The SRB was removed, washed in AcOH (1%) and allowed to air-dry. Then aqueous Tris base [tris(hydroxymethyl)aminoethane] (100 µL, 10 mM) was added to each well to solubilize the cell-bound dye and the absorbance at 550 nm was measured. The results are expressed as a percentage of control cell growth.

18

2,2-Diphenyl-1,3,2-oxazaborolidin-5-one (3a): White solid; mp 241-243 °C (Lit. 242-245 °C); IR (KBr): 3428, 3243, 3074, 1720, 1604, 1434, 1302, 1217, 963, 702 cm-1; 1H NMR (DMSO-d 6 ): δ = 7.35 (d, J = 7 Hz, 4 H), 7.22 (t, J = 7 Hz, 4 H), 7.16 (t, J = 7 Hz, 4 H), 7.07 (br t, 2 H, NH), 3.43 (t, J = 6 Hz, 2 H); 13C NMR (DMSO-d 6 ): δ = 42.9, 126.1, 127.1, 131.0, 147.8, 172.5; 11B NMR (DMSO-d 6 ): δ = +5.03; MS (EI): m/z = 239, 238, 162 (base peak), 161, 132, 104, 77.