Synthesis of DL-standishinal and its related compounds for the studies on structure-activity relationship of inhibitory activity against aromatase
Synthesis of DL-standishinal and its related compounds for the studies on structure-activity relationship of inhibitory activity against aromatase
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DOI：
10.1016/j.bmc.2007.01.031
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发表时间：
2007-04-01
影响因子：
3.5
通讯作者：
Saito, Koichi
中科院分区：
文献类型：
--
作者：
Katoh, Takahiro;Akagi, Taichi;Saito, Koichi
以对甲酰基苯甲醚为起始原料，经12-羟基-6，7-开环松香-8，11，13-三烯-6，7-二醛（2）的羟醛缩合反应，经15步反应合成了从崖柏中分离得到的芳香化酶抑制剂DL-斯坦迪辛醛（1）。在本研究中，我们发现2的羟醛缩合反应在质子催化剂如d-异丙基磺酸的二氯甲烷中以优异的产率进行。此外，还对1及其相关化合物的构效关系进行了研究，发现A/B环上具有顺式构型的异构体比反式构型的异构体具有更强的芳香化酶抑制活性。(c)2007爱思唯尔有限公司保留所有权利。
DL-Standishinal (1), an aromatase inhibitor isolated from Thuja standishii, was synthesized in 15 steps from p-formylanisole via aldol reaction of 12-hydroxy-6,7-secoabieta-8,11,13-trien-6,7-dial (2). In the present study, we found that the aldol condensation of 2 proceeded in excellent yield with the protonic catalyst such as d-camphorsulfonic acid in CH2Cl2. Moreover, structure-activity relationship of 1 and its related compounds was studied and it was revealed that the isomers having cis-configuration on the A/B-ring generally exhibited more potent inhibitory activities against aromatase than those with trans-configuration. (c) 2007 Elsevier Ltd. All rights reserved.