Shao Ning, Xue Jie, Guo Zhongwu
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
J Org Chem. 2003 Nov 14;68(23):9003-11. doi: 10.1021/jo034773s.
Glycopeptide 1 with the fucosylated trisaccharide, beta-d-GlcNAc(1-->4)[alpha-l-Fuc(1-->6)]-beta-d-GlcNAc, linked to the Asn of CD52 peptide was prepared by two methods, both of which used the free glycosyl Asn 12 and glycotripeptide 21 as key intermediates. Thus, after the trisaccharide was prepared and linked to Asn, the carbohydrate moiety was deprotected to give 12. From 12, 21 was constructed in homogeneous NMP solutions by elongating the peptide chain alone the N-terminus. Though the glycopeptides were easily soluble in NMP, they were barely soluble in diethyl ether, because of the free trisaccharide. Consequently, addition of diethyl ether to the reaction mixtures could precipitate the glycopeptides, and the products were conveniently isolated and purified in the solid form. The coupling of 21 with a free nonapeptide 24 in NMP afforded 1. 1 was also prepared by solid-phase synthesis, using the acid-sensitive 2-chlorotrityl resin. In this case, 21 was attached to the nonapeptide on the resin, and the resulting glycopeptide was then released with dilute acetic acid. Deprotection of the peptide under moderate acidic conditions gave 1. The acid-labile alpha-fucose was not affected in these syntheses.
通过两种方法制备了糖肽1，其岩藻糖基化三糖β-d- GlcNAc(1→4)[α-l-Fuc(1→6)]-β-d- GlcNAc与CD52肽的天冬酰胺相连，这两种方法均使用游离糖基天冬酰胺12和糖三肽21作为关键中间体。因此，在制备三糖并将其与天冬酰胺连接后，对碳水化合物部分进行脱保护得到12。从12开始，通过仅在N端延长肽链，在均相NMP溶液中构建21。尽管糖肽易溶于NMP，但由于游离三糖的存在，它们几乎不溶于乙醚。因此，向反应混合物中加入乙醚可使糖肽沉淀，产物以固体形式方便地分离和纯化。在NMP中，21与游离九肽24偶联得到1。1也通过使用对酸敏感的2-氯三苯甲基树脂的固相合成法制备。在这种情况下，21连接到树脂上的九肽上，然后用稀乙酸释放得到的糖肽。在适度酸性条件下对肽进行脱保护得到1。在这些合成中，酸不稳定的α-岩藻糖不受影响。
