Design and synthesis of boron containing potential pan-RAR inverse agonists
Design and synthesis of boron containing potential pan-RAR inverse agonists
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DOI：
10.1016/j.tetlet.2011.12.118
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发表时间：
2012-03-14
影响因子：
1.8
通讯作者：
Evans, Todd
中科院分区：
文献类型：
--
作者：
Das, Bhaskar C.;Tang, Xiang-Ying;Evans, Todd
我们设计并成功合成了化合物5和8作为潜在的泛rar（视黄酸受体）激动剂。这两种化合物是基于现有的泛rar激动剂（BMS493）设计的。我们合成了化合物5，其中BMS 493中的羧基被硼酯取代；化合物8，其中BMS 493的双键变成了一个恶二唑（作为双键的生物同位异构体）环。两个目标分子5和8是由市售的7-溴-4,4-二甲基-3,4-二氢萘-1(2H)- 1合成的。化合物1经烷基化、脱水和金属交换反应衍生为中间体5,5-二甲基-8-（苯乙基）-5,6-二氢萘-2 -乙醛4。中间体4通过Wittig反应进一步转化为5，通过酰胺偶联和脱水进一步转化为8，每种情况下经过8个步骤，总收率分别为18%和33%。(C) 2011 Elsevier Ltd.版权所有。
We designed and successfully synthesized the compounds 5 and 8 as potential pan-RAR (retinoic acid receptor) agonists. These two compounds were designed based on an existing pan-RAR agonist (BMS493). We synthesized compound 5, in which the carboxylic acid group in BMS 493 was replaced by boronic ester; and compound 8, in which the double bond of BMS 493 was changed to an oxadiazole (as bioisosteres of double bond) ring. The two target molecules 5 and 8 were synthesized from the commercially available 7-bromo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one 1. Compound 1 was derivatized to intermediate 5,5-dimethyl-8-(phenylethynyl)-5,6-dihydronaphthalene-2 carbaldehyde 4 by using alkylation, dehydration, and metal exchange reactions. The intermediate 4 was further converted to 5 by using a Wittig reaction and to 8 by amide coupling and dehydration to give overall 18% and 33% yields, respectively, after 8 steps in each case. (C) 2011 Elsevier Ltd. All rights reserved.