64100-61-4Relevant articles and documents
Enantioselective and diastereoselective hydroxylation of bufuralol. Absolute configuration of the 7-(1-hydroxyethyl)-2-[1-hydroxy-2-(tert-butylamino)ethyl]benzofurans, the benzylic hydroxylation metabolites
Weerawarna,Geisshusler,Murthy,Nelson
, p. 3091 - 3097 (1991)
Asymmetric synthesis of the diastereomeric 7-(1-hydroxyethyl)-2-[1-hydroxy-2-(tert-butylamino)ethyl]benzofurans (2), the benzylic hydroxylation metabolites of bufuralol (1), is described, and the absolute configurations of these diastereomers are assigned. 1''-Oxobufuralol (3) was reduced with a complex of (2S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol and borane, yielding 2, which had a 95:5 ratio of the possible 1''R and 1''S isomers as determined by HPLC. Separation of the resulting diastereomers was facilitated by derivatization with the enantiomers of 1-phenethyl isocyanate (PEIC). The absolute configurations 1'S.,''R and 1'R,1''R were assigned to the diastereomers formed in excess, 2c and 2b, on the basis of the known stereochemistry of reduction of closely related alkyl phenyl ketones to R alcohols by using this chiral borane reagent. The circular dichroism spectra of the four isomeric benzylic alcohols were in agreement with these assignments. In the presence of the rat liver microsomal fraction, benzylic hydroxylation of bufuralol was significantly product stereoselective favoring formation of diastereomers with the 1''R absolute stereochemistry at the new chiral center in products from (1'R)-1 by a ratio of 4.5:1 [(1'R,1''R)-2:(1'R,1''S)-2] and by nearly 8:1 [(1'S,1''R)-2:(1'S,1''S)-2] from (1'S)-1. (1'R)-Bufuralol was more rapidly hydroxylated than was (1'S)-1, by about 3-fold. In the presence of human liver microsomes, (1'R)-bufuralol was also more rapidly hydroxylated than was (1'S)-1, by ca. 2.5-fold. However, product stereoselectivity from the 1'R enantiomer was reversed from that observed in the rat liver microsomal oxidation, with more (1''S)-carbinol being formed than 1''R isomer by nearly 4-fold. From (1'S)-1, about equal amounts of the two possible hydroxybufuralol diastereomers were formed. The results from the human liver microsomal studies are consistent with observed enantioselectivity of hydroxylation of bufuralol in vivo in humans.
Asymmetric synthesis of β-amino alcohols by the transfer hydrogenation of α-keto imines
Tafelska-Kaczmarek, Agnieszka,Prewysz-Kwinto, Andrzej,Skowerski, Krzysztof,Pietrasiak, Katarzyna,Kozakiewicz, Anna,Zaidlewicz, Marek
experimental part, p. 2244 - 2248 (2010/11/03)
The asymmetric transfer hydrogenation of representative aryl and benzofuranyl 2-tert-butylaminoethanones with formic acid-triethylamine, catalyzed by RhCl[(R,R)-TsDPEN](C5Me5), produced the corresponding β-tert-butylamino alcohols in 97-99% ee. A short asymmetric synthesis of (R)-bufuralol, a potent β-adrenergic receptor antagonist, is described. This approach to β-amino alcohols from ketones circumvents the halogenation-reduction-amination sequence.
Chiral separations of some β-adrenergic agonists and antagonists on AmyCoat column by HPLC
Ali, Imran,Saleem, Kishwar,Gaitonde, Vinay D.,Aboul-Enein, Hassan Y.,Hussain, Iqbal
experimental part, p. 24 - 28 (2010/09/14)
Sixteen β-adrenergic antagonists namely acebutalol, alprenolol, atenolol, bisoprolol, bopindolol, bufurolol, carazolol, celiprolol, indenolol, metaprolol, nebivolol, oxprenolol, practolol, propranolol, tertalol, and timolol, and two β-adrenergic agonists namely cimeterol and clenbuterol were resolved on AmyCoat (150 x 46 mm, 3 μm size of silica particle) by using (85:15:0.1, v/v/v), (90:10:0.1, v/v/v), and (95:05:0.1, v/v/v) combinations of η-heptane, ethanol, and diethylamine solvents, respectively. The flow rates used were 0.5, 1.0, 2.0, and 3.0 ml/min with detection at 225 nm. The values of capacity, separation, and resolution factors ranged from 0.38 to 19.70, 1.08-2.33, and 1.0 and 4.50, respectively. The maximum and minimum resolutions were achieved for celiprolol and bufurolol, respectively. The chiral recognition mechanisms were also discussed. The values of validation parameters were calculated.
