Use of fluorobenzoyl protective groups in synthesis of glycopeptides: beta-elimination of O-linked carbohydrates is suppressed

Fluorobenzoyl groups have been investigated as alternatives to acetyl and b enzoyl protective groups in carbohydrate and glycopeptide synthesis. D-Gluc ose and lactose were protected with different fluorobenzoyl groups and then converted into glycosyl bromides in high yields (> 80% over two steps). Gl ycosylation of protected derivatives of serine with these donors gave 1,2-t rans glycosides in good yields (similar to 60-70%) and excellent stereosele ctivity 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-difluorobe nzoyl 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. Fluo robenzoyl groups thus combine the advantages of the benzoyl group in format ion of glycosidic bonds (i.e., high stereoselectivity and low levels of ort ho eater formation) with the ease of removal characteristic of the acetyl g roup.