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

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11 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

Bibliographical note

Funding Information:
We thank Professor Gary R. Gray for critical reading of the manuscript and William W. Brennessel of the X-ray Crystallographic Laboratory of the Department of Chemistry at the University of Minnesota for assistance in solving the structure of 5 . An anonymous referee made several helpful suggestions, which are appreciated insofar as they guided revision of the manuscript. This work was supported by grant GM 66148 from the National Institute of Health.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

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

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