化学
环加成
非对映体
法尼酰转移酶
甲苯
加合物
选择性
立体化学
法尼酰转移酶抑制剂
有机化学
催化作用
酶
预酸化
作者
Nicolas Pichon,Anne Harrison‐Marchand,Patrick Mailliet,Jacques Maddaluno
摘要
The access to several benzo[f]perhydroisoindolic analogues of farnesyltransferase inhibitors from a single dienic precursor is reported. An initial [4 + 2] cycloaddition between diphenylisobenzofuran 6 and pyrrolines 11, 14, and 15 led to either the syn or the anti isomers, depending on the mode of activation of the cycloaddition. The syn diastereomers were isolated in 90% de under 12 kbar at room temperature, while their anti counterparts were obtained with the same selectivity by warming the reaction mixture to 110 °C in toluene at atmospheric pressure. Both syn and anti adducts were separately N-deprotected, and the resulting amines reacted with an activated ester derived from the acid (20) to afford the final targets (5). Two new analogues (5a and 5b) of the FT inhibitor RPR 130401 were thus synthesized in a mere three-step synthetic scheme with overall yields from 30 to 60%.
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