Syntheses of TN building blocks Nα-(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

Mian Liu, Victor G. Young, Sachin Lohani, David Live, George Barany

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

TN antigen building blocks Nα-(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(Ac3-α-d-GalN3)-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-d3. 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.

Original languageEnglish (US)
Pages (from-to)1273-1285
Number of pages13
JournalCarbohydrate Research
Volume340
Issue number7
DOIs
StatePublished - May 23 2005

Keywords

  • Dehydroalanine
  • Glycopeptide synthetic building blocks
  • Glycosylation
  • Metal ion-carbohydrate complexes
  • Side reactions
  • Z-Dehydrothreonine

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