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Preparation of Novel Delivery Agents for Delivery of Macromolecular Drugs Using Boric Acid Mediated Amidation of Carboxylic Acids and Amines

机译:使用硼酸介导的羧酸和胺介导的新型递送剂的制备用于递送大分子药物

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Delivery agents comprising a carboxamide moiety are useful for the delivery of macromolecular drugs to the systemic circulation via oral administration. A practical synthetic pathway to these delivery agents has been developed by the direct amidation between a carboxylic acid and an amine using a catalytic amount of boric acid as a mediator. Boric acid is nontoxic, environmentally safe, and inexpensive. This method eliminates the preparation of acid chlorides, and is amenable for large-scale preparation providing excellent yields of the desired carboxamides. This boric acid mediated amidation between the carboxylic acids and amines with a variety of functional groups was achieved in a simple, single-step process using a equal molar mixture of acids and amines. This amidation works well with weakly nucleophilic amine, such as arylamines. The utility of the boric acid mediated amidation will be discussed.
机译:包含甲酰胺部分的递送剂可用于通过口服给药将大分子药物输送到全身循环中。通过使用催化量的硼酸作为介体,通过直接酰胺化产生对这些递送剂的实际合成途径已经通过羧酸和胺之间的直接酰胺化。硼酸是无毒,环保,廉价的。该方法消除了酰氯的制备,并且适用于大规模制剂,提供所需羧酰胺的优异产率。使用酸和胺的等步骤方法,在简单的单步工艺中介导羧酸和胺之间介导羧酸和胺之间的胺化。这种胺化适用于弱亲核胺,例如芳基胺。将讨论硼酸介导的胺化的效用。

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