Nelson W L, Powell M L, Dyer D C
J Med Chem. 1979 Sep;22(9):1125-7. doi: 10.1021/jm00195a024.
The enantiomers of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane (4) were prepared from the chiral 2-[(tosyloxy)methyl]-1,4-benzodioxanes [(2S)- and (2R)-5]. The corresponding (2R)- and (2S)-2-(aminoethyl)-1,4-benzodioxanes [2R)- and (2S)-7] were prepared by a modified Gabriel synthesis and converted to the enantiomers of 4 by condensation with 2,6-dimethoxyphenoxyacetaldehyde (8) and reduction of the intermediate imine with NaBH4. The enantiomer (2S)-4 was 40--50 times as potent as the enantiomer (2R)-4 in antagonizing the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips, showing a pA2 = 9.0. This result is consistent with the previous observation that S enantiomers of 2-[(alkylamino)methyl]benzodioxanes are more potent antagonists at a alpha-adrenergic receptors than the R enantiomers.
2-[[[2-(2,6-二甲氧基苯氧基)乙基]氨基]甲基]-1,4-苯并二恶烷(4)的对映体由手性2-[(对甲苯磺酰氧基)甲基]-1,4-苯并二恶烷[(2S)-和(2R)-5]制备。相应的(2R)-和(2S)-2-(氨基乙基)-1,4-苯并二恶烷[(2R)-和(2S)-7]通过改良的盖布瑞尔合成法制备，并通过与2,6-二甲氧基苯氧基乙醛(8)缩合以及用硼氢化钠还原中间体亚胺转化为4的对映体。对映体(2S)-4在拮抗甲氧明诱导的兔主动脉条收缩的α-肾上腺素能反应方面的效力是对映体(2R)-4的40至50倍，pA2 = 9.0。该结果与先前的观察结果一致，即2-[(烷基氨基)甲基]苯并二恶烷的S对映体在α-肾上腺素能受体上比R对映体是更强效的拮抗剂。
