About the chameleonic behaviour of some β1 and β2 adrenergic ligands

Synthesis of Homochiral 5- and 8- Substituted 2-[((2-(2,6-Dimethoxyphenoxy)- ethyl)amino)methyl]-1,4-benzodioxanes and Electrophoretic Determination of Their Enantiomeric Excess

“…In fact, only the S isomers proved to be more than 99.6% enantiomerically pure, while the enantiomeric excesses of the R forms were 95.95% and 96.97%, respectively. These results indicate the higher enantioselectivity of the present syntheses, based on the initial efficient resolution of glycerol acetonide and on the successive transformations illustrated in Scheme , in comparison with the previously described syntheses of the R isomers of WB4101 and 2-(aminomethyl)-1,4-benzodioxane hydrochloride, ,, consisting in using the same antipod of glycerol acetonide as for the preparation of the S isomers of the above compounds and in formally exchanging the attachment site of the functional groups at the glycerol moiety.…”

“…The electophoretic analysis of the optical antipodes of 1 − 3 , under the above specified conditions, allowed one to determine invariably higher than 99.6% enantiomeric excesses. On the contrary, in the case of WB4101 and 2-(aminomethyl)-1,4-benzodioxane hydrochloride, the S and the R forms, both previously prepared from ( S )-glycerol acetonide by two different synthetic pathways according to literature methods, ,, showed disparity in stereoisomeric purity. In fact, only the S isomers proved to be more than 99.6% enantiomerically pure, while the enantiomeric excesses of the R forms were 95.95% and 96.97%, respectively.…”

“…Among the structures which have the capacity to interact with α 1 -adrenoceptors, benzodioxanes are one of the main classes. In particular, WB4101, which can be considered the lead compound of such a class, exhibits a nanomolar affinity toward α 1 -adrenoceptor, the S enantiomer possessing remarkably higher affinity than the R enantiomer . As part of our ongoing program aimed at the study of chiral benzodioxane derivatives as type-selective α-adrenoceptor ligands, we wish to report herein the synthesis of the enantiomers of the 5-methoxy, 8-methoxy, and 8-fluoro analogues ( 1 − 3 ; see Chart ) of WB4101 and, in addition, a practical method to determine their enantiomeric excess.…”

2,6‐Difluorobenzamide Inhibitors of Bacterial Cell Division Protein FtsZ: Design, Synthesis, and Structure–Activity Relationships

“…In this context, in our attempt to design and develop novel antibacterial agents, we created several derivatives in recent years, replacing the thiazolopyridine of PC190723 with differently substituted 1,4‐benzodioxane, a heterocyclic scaffold extensively studied by our research group . Among these, the most promising derivatives were I , II , and III , reported in Figure .…”

Resolution of 2-substituted 1,4-benzodioxanes by entrainment

“…These methods are based on resolution of the respective racemates, catalyzed by enzymes 1,2 or accomplished after conversion into diastereomeric mixtures, 3,4 or on syntheses, which utilize asymmetric catalysts or start from non-racemic precursors belonging to the 'chiral pool', such as glycerol or glycidol derivatives. [5][6][7][8] The most recent examples, reported after 2000, are the palladium-catalyzed asymmetric cyclization of benzene-1,2-diol with allylic biscarbonates, 9 the palladium-catalyzed intramolecular cyclization of non-racemic 1-(2-bromophenyl)glycerol 10 and the enzymatic resolutions of 1,4-benzodioxane-2-carboxylic acid, 11 its ethyl ester 12 and 2-hydroxymethyl-1,4-benzodioxane. 13 In 2003, we developed some efficient resolution methods for 1,4-benzodioxane-2-carboxylic acid with (+)-dehydroabietylamine, giving access to both enantiopure (R)-and (S)-acids.…”