N-diphenylmethylene-protected glycosyl acceptors. Selective β-O-glycosylation to form lactosyl-threo-ceramides

Matt A. Peterson, Robin L Polt

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A series of N-diphenylmethylene-protected sphingosine derivatives was synthesized (e.g 3a,b and 9a,b). These compounds are efficient glycosyl acceptors and were shown to undergo highly β-selective glycosylation using a modification of the Koenigs-Knorr reaction previously used in this laboratory for the synthesis of O-linked glycopeptides (none of the α-anomers were detected by either 1H or 13C NMR).1 The N-diphenylmethylene (Schiff base) protection imparts a favorable intramolecular hydrogen-bonding pattern (Ph2C=N:→H-O:). This intramolecular hydrogen-bonding enhances the nucleophilicity of the glycosyl acceptor relative to glycosyl acceptors with more conventional N-protection (i.e. Cbz, Boc, acyl etc.). The enhanced nucleophilicity allowed the glycosylation to be carried out under mild conditions (AgOTfl, CH2Cl2, rt overnight), and provided the corresponding β-glycosphingolipids 4a-c and 11a-d in excellent chemical yield (approximately 70%). After glycosylation, selective acid-catalyzed hydrolysis of the Schiff base protecting group was accomplished without cleavage of the glycosidic bond or the carbohydrate acetate protection. N-Acylation with palmitoyl chloride, followed by Zemplèn deacetylation (cat. NaOMe in MeOH), provided the two threo-β-lactosylcerainide analogues 7a and 7b. These analogues possess the unnatural threo-configuration in the ceramide moiety and may prove useful in studies of the biosynthesis and cell surface composition of more complex glycosphingolipids.

Original languageEnglish (US)
Pages (from-to)4309-4314
Number of pages6
JournalJournal of Organic Chemistry
Volume58
Issue number16
StatePublished - 1993

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Glycosylation
Ceramides
Glycosphingolipids
Schiff Bases
Hydrogen bonds
Acylation
Sphingosine
Glycopeptides
Biosynthesis
Surface structure
Hydrolysis
Acetates
Carbohydrates
Nuclear magnetic resonance
Derivatives
Acids

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

N-diphenylmethylene-protected glycosyl acceptors. Selective β-O-glycosylation to form lactosyl-threo-ceramides. / Peterson, Matt A.; Polt, Robin L.

In: Journal of Organic Chemistry, Vol. 58, No. 16, 1993, p. 4309-4314.

Research output: Contribution to journalArticle

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