O‐Glycosyl Amino Acids by 2‐Nitrogalactal Concatenation − Synthesis of a Mucin‐Type O‐Glycan

Abstract

Base‐promoted Michael‐type addition of N‐Boc‐ and N‐Fmoc‐protected serine and threonine esters to 2‐nitrogalactal derivatives 2 and 26 led highly selectively to α‐glycosides 4a−d and 27a,c, respectively. Ensuing transformation of threonine derivative 4d and serine derivatives 4a,b resulted in compounds useful as lysine and dipeptide mimetics. 6‐O‐Desilylation of 27a,c, then 6‐O‐sialylation, and transformation of the nitro group of the galactose moiety into a 2‐acetamido functionality, afforded N‐Boc‐protected serine and threonine tert‐butyl esters 31a,c carrying the O‐protected STN‐antigen at the hydroxy group. The threonine derivative 31c was then transformed into the N‐Fmoc‐protected amino acid building block 33, which was employed for the synthesis of mucin repeating unit partial structure Ac‐GS(STN)‐TAPPAHG‐NH2 (1). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Linear synthesis and immunological properties of a fully synthetic vaccine candidate containing a sialylated MUC1 glycopeptide

“…18 Although great care was taken in the deprotection of the methyl ester of the sialoside using mild basic conditions, it resulted mainly in β-elimination of the glycan. A benzyl ester protected sialic acid derivative 19 was not considered because its deprotection would be difficult to accomplish on the target glycolipopeptides.…”

A Convenient Synthesis of Pyrano[2,3‐b][1,5]oxazepines by Ring Closure of O‐Glycosyl Amino Acids

“…[13][14][15] In this way, galactoside 1aα and 1bα can be readily obtained from 3,4,6-tri-O-benzyl-2-nitrogalactal [13] and N-Boc-protected serine tert-butyl and methyl ester, respectively [16] (Scheme 2). Reduction of the nitro group in the presence of platinized Raney-nickel [27] as catalyst afforded the amino derivative 2aα, [16] which, on treatment with fluorenylmethyloxycarbonyl chloride (FmocCl) in the presence of triethylamine, afforded N,O-protected intermediate 3aα. Acid-catalyzed cleavage of the Boc group and of the tert-butyl ester led to formation of the versatile intermediate 4α; attachment of a Boc group to the amino group furnished the orthogonally protected O-glycosyl serine derivative 5α.…”

“…[11] O-Glycosylation of β-hydroxycarboxylates and, particularly, of serine and threonine, having α-amino groups, with glycosyl donors derived from 2-amino-2-deoxy sugars leads to versatile building blocks for glycopeptide synthesis and for the generation of glycopeptide mimetics, and for various functional group manipulations. [12] The versatile direct base-catalyzed addition of O-, N-, C-, and S-nucleophiles to 2-nitroglycals (Scheme 1), as recently investigated by us, [13][14][15][16][17][18][19][20][21][22] have made these building blocks readily available.…”

Antibodies against Mucin‐Based Glycopeptides Affect Trypanosoma cruzi Cell Invasion and Tumor Cell Viability

“…13 Accordingly, truncated O ‐GalNAc glycans including Tn (αGalNAcSer/Thr), STn (Siaα2–6αGalNAcSer/Thr), and Thomsen–Friedenreich (TF or T‐antigen, Galβ1–3αGalNAcSer/Thr) antigens are found exposed on tumor cells (Scheme ), in which their aberrant and abundant expression confers on them the classification of tumor‐associated carbohydrate antigens (TACAs), with functional properties of adhesion, invasion, and metastasis 1. 10, 14–24 As can be seen in recent literature, the involvement of TACA structures in inducing active immunity and their limited occurrence in normal tissues make them valuable targets for immunotherapy against cancer 20–23…”