Syntheses of T N building blocks N α-(9-fluorenylmethoxycarbonyl)- O-(3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-galactopyranosyl)- l-serine/ l-threonine pentafluorophenyl esters: comparison of protocols and elucidation of side reactions

• Published in: Carbohydrate research Vol. 340; no. 7; pp. 1273 - 1285
• Main Authors: Liu, Mian, Young, Victor G., Lohani, Sachin, Live, David, Barany, George
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 23.05.2005
• Subjects: Dehydroalanine; Glycopeptide synthetic building blocks; Glycosylation; Metal ion–carbohydrate complexes; Side reactions; Z-Dehydrothreonine; Side reactions; Glycosylation; Z-Dehydrothreonine; Dehydroalanine; Metal ion–carbohydrate complexes; Glycopeptide synthetic building blocks
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2005.02.029

[Display omitted] T N antigen building blocks N α-(9-fluorenylmethoxycarbonyl)- O-(3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-galactopyranosyl)- l-serine/ l-threonine pentafluorophenyl ester [Fmoc- l-Ser/ l-Thr(Ac 3-α- d-GalN 3)-OPfp, 13/ 14] have been synthesized by two different routes, which have been compared. Overall isolated yields [three or four chemical steps, and minimal intermediary purification steps] of enantiopure 13 and 14 were 5–18% and 6–10%, respectively, based on 3,4,6-tri- O-acetyl- d-galactal ( 1). A byproduct of the initial azidonitration reaction of the synthetic sequence, that is, N-acetyl-3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-galactopyranosylamine ( 5), has been characterized by X-ray crystallography, and shown by 1H NMR spectroscopy to form complexes with lithium bromide, lithium iodide, or sodium iodide in acetonitrile- d 3. Intermediates 3,4,6-tri- O-acetyl-2-azido-2-deoxy-α- d-galactopyranosyl bromide ( 6) and 3,4,6-tri- O-acetyl-2-azido-2-deoxy-β- d-galactopyranosyl chloride ( 7) were used to glycosylate N α-(9-fluorenylmethoxycarbonyl)- l-serine/ l-threonine pentafluorophenyl esters [Fmoc- l-Ser/ l-Thr-OPfp, 11/ 12]. Previously undescribed low-level dehydration side reactions were observed at this stage; the unwanted byproducts were easily removed by column chromatography.