Oatis J E, Walle T, Daniell H B, Gaffney T E, Knapp D R
J Med Chem. 1985 Jun;28(6):822-4. doi: 10.1021/jm00383a023.
4'-Hydroxypropranolol sulfate was recently identified as a major metabolite of propranolol (Inderal). In order to confirm the structure and to further study disposition and biological activity, we have synthesized 8 with use of 1,4-naphthoquinone as the starting material. Reduction and alkylation with benzyl iodide gave 4-(benzyloxy)naphthol. Sulfation and chlorosulfuric acid in N,N-dimethylaniline gave potassium 1-(benzyloxy)-4-naphthol sulfate. Catalytic hydrogenation, alkylation with [[[(trifluoromethyl)sulfonyl]oxy]methyl]oxirane, and amination in isopropylamine gave 8. Racemic 8 was found to be 100-1000 times less potent than racemic propranolol as a beta-adrenergic receptor blocking agent in the dog.
4'-羟基普萘洛尔硫酸盐最近被确认为普萘洛尔（心得安）的主要代谢产物。为了确定其结构并进一步研究其处置情况和生物活性，我们以1,4-萘醌为起始原料合成了8。用苄基碘进行还原和烷基化反应得到4-(苄氧基)萘酚。在N,N-二甲基苯胺中用硫酸化试剂和氯磺酸进行反应得到1-(苄氧基)-4-萘酚硫酸钾。通过催化氢化、用[[[(三氟甲基)磺酰基]氧基]甲基]环氧乙烷进行烷基化反应以及在异丙胺中进行胺化反应得到8。在犬体内，外消旋的8作为β-肾上腺素能受体阻断剂，其效力比外消旋普萘洛尔低100至1000倍。
