阿基瑞林制备方法的改进研究

阿基瑞林，又称乙酰基六肽-8、六胜肽等。它作为肉毒毒素的安全替代品，具有显著的抗皱活性，是美妆市场上需求潜力很大的抗皱多肽原料。当前阿基瑞林主要是通过固相合成方法得到的，由于所使用的Rink Amide AM树脂单价高、上载量低，造成了阿基瑞林原料价格高昂，不利于其大规模生产及推广应用。本文中使用固-液相结合的方法，首先用高上载量、单价低的2-CTC树脂合成六肽片段，六肽片段再经酰胺化处理得阿基瑞林粗品，粗品经纯化后得纯度95%以上的阿基瑞林，收率59.77%。本方法成本低、收率高，为C端酰胺化多肽的合成提供了一种新思路。

Study on the improvement of preparation method of argireline

Argireline, also known as Acetyl Hexapeptide-8 and Hexapeptide. As a safe alternative of botulinum toxin, it has significant anti-wrinkle activity and is a potential anti-wrinkle peptide material in beauty makeup market. At present, Argireline is mainly obtained by solid phase synthesis. However, due to high unit price, low uploading quantity and low yield of Rink Amide AM Resin used, the raw material price of Argireline is high, which is not conducive to its large-scale production and application. In this paper, the method of solid-liquid phase combination was used: first, hexapeptide fragment was synthesized with 2-CTC Resin with high loading capacity and low unit price. Hexapeptide fragment was aminated to get crude achirylin. After purification, more than 95% achirylin was obtained with 59.77% yield. Compared with Rink Amide AM Resin, the synthesis cost of 2-CTC Resin decreased by 19.74% per kilogram and the yield increased by 13.25%. Rink Amide AM Resin and 2-CTC Resin yield per kilogram of large-scale production batches increased from 406.4g to 908.0g. This method provides a new idea for the synthesis of C-terminal aminated polypeptides.