Piettre S R, André C, Chanal M C, Ducep J B, Lesur B, Piriou F, Raboisson P, Rondeau J M, Schelcher C, Zimmermann P, Ganzhorn A J
Marion Merrell Research Institute, Strasbourg, France.
J Med Chem. 1997 Dec 19;40(26):4208-21. doi: 10.1021/jm9701942.
The first successful preparation of mono- and disubstituted 3,7-dihydroxytropolone involves a four-step synthetic scheme. Thus, bromination of 3,7-dihydroxytropolone (8) followed by permethylation of the resultant products furnished gram quantities of intermediates 13-18. Single or double Suzuki coupling reactions between these permethylated monobromo- and dibromodihydroxytropolone derivatives and a variety of boronic acids delivered the expected products whose deprotection yielded the desired compounds 1a-u and 26a-n, usually in fair to good yields. Tropolones 1 and 26 were found to be potent inhibitors of inositol monophosphatase with IC50 values in the low-micromolar range. The results are discussed in the context of the recently described novel mode of inhibition of the enzyme by 3,7-dihydroxytropolones.
单取代和双取代3,7 - 二羟基环庚三烯酚酮的首次成功制备涉及一个四步合成方案。因此，3,7 - 二羟基环庚三烯酚酮（8）的溴化反应，随后对所得产物进行全甲基化反应，得到了克级量的中间体13 - 18。这些全甲基化的单溴代和二溴代二羟基环庚三烯酚酮衍生物与各种硼酸之间的单步或双步铃木偶联反应得到了预期产物，其脱保护反应通常以相当好的产率得到所需化合物1a - u和26a - n。发现环庚三烯酚酮1和26是肌醇单磷酸酶的有效抑制剂，IC50值在低微摩尔范围内。在最近描述的3,7 - 二羟基环庚三烯酚酮对该酶的新型抑制模式的背景下对结果进行了讨论。
