Brun Omar, Elduque Xavier, Pedroso Enrique, Grandas Anna
Departament de Química Orgànica, Facultat de Química and IBUB, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
J Org Chem. 2015 Jun 19;80(12):6093-101. doi: 10.1021/acs.joc.5b00592. Epub 2015 Jun 1.
The reaction between maleimides and resin-linked diene-polyamides allows the latter to be used in the preparation of conjugates. Conjugation takes place by reacting the insoluble, hydrophobic diene component either with water-soluble dienophiles or with dienophiles requiring mixtures of water and organic solvents. Experimental conditions can be adjusted to furnish the target conjugate in good yield with no need of adding large excesses of soluble reagent. In case protected maleimides are used, maleimide deprotection and Diels-Alder cycloaddition can be simultaneously carried out to render conjugates with different linking positions. On-resin conjugation is followed by an acidic treatment that removes the polyamide protecting groups with no harm to the cycloadduct, in contrast with the unreacted diene that is indeed degraded under these conditions. Cycloadducts incorporating suitable functional groups can undergo subsequent additional conjugation reactions in solution to furnish double conjugates.
马来酰亚胺与树脂连接的二烯 - 聚酰胺之间的反应使得后者可用于制备缀合物。缀合反应是通过使不溶性的疏水性二烯组分与水溶性亲双烯体或需要水和有机溶剂混合物的亲双烯体反应来进行的。可以调整实验条件以高收率提供目标缀合物，而无需加入大量过量的可溶性试剂。如果使用受保护的马来酰亚胺，则可以同时进行马来酰亚胺脱保护和狄尔斯 - 阿尔德环加成反应，以得到具有不同连接位置的缀合物。树脂上的缀合反应之后进行酸性处理，该处理可以除去聚酰胺保护基团而不损害环加合物，这与在这些条件下确实会降解的未反应二烯形成对比。含有合适官能团的环加合物可以在溶液中进行后续的额外缀合反应以提供双缀合物。
