Sjölin P, Kihlberg J
Organic Chemistry, Department of Chemistry, Umeå University, SE--901 87 Umeå, Sweden.
J Org Chem. 2001 May 4;66(9):2957-65. doi: 10.1021/jo001584q.
Fluorobenzoyl groups have been investigated as alternatives to acetyl and benzoyl protective groups in carbohydrate and glycopeptide synthesis. D-Glucose and lactose were protected with different fluorobenzoyl groups and then converted into glycosyl bromides in high yields (>80% over two steps). Glycosylation of protected derivatives of serine with these donors gave 1,2-trans glycosides in good yields (approximately 60--70%) and excellent stereoselectivity without formation of ortho esters. The resulting glycosylated amino acid building blocks were then used in solid-phase synthesis of two model O-linked glycopeptides known to be unusually sensitive to beta-elimination on base-catalyzed deacylation. When either a 3-fluoro- or a 2,5-difluorobenzoyl group was used for protection of each of the two model glycopeptides the extent of beta-elimination decreased from 80% to 10% and from 50% to 0%, respectively, as compared to when using the ordinary benzoyl group. Fluorobenzoyl groups thus combine the advantages of the benzoyl group in formation of glycosidic bonds (i.e., high stereoselectivity and low levels of ortho ester formation) with the ease of removal characteristic of the acetyl group.
在碳水化合物和糖肽合成中，氟苯甲酰基已被研究作为乙酰基和苯甲酰基保护基的替代物。用不同的氟苯甲酰基保护D-葡萄糖和乳糖，然后高产率（两步反应产率>80%）转化为糖基溴化物。这些供体与丝氨酸的保护衍生物进行糖基化反应，以良好的产率（约60-70%）和优异的立体选择性得到1,2-反式糖苷，且不形成原酸酯。然后，将所得的糖基化氨基酸构建块用于两种已知对碱催化脱酰基β-消除异常敏感的O-连接糖肽模型的固相合成。当使用3-氟苯甲酰基或2,5-二氟苯甲酰基保护这两种糖肽模型时，与使用普通苯甲酰基相比，β-消除程度分别从80%降至10%和从50%降至0%。因此，氟苯甲酰基结合了苯甲酰基在形成糖苷键方面的优点（即高立体选择性和低原酸酯形成水平）以及乙酰基易于去除的特性。
