Chemical synthesis and seroreactivity of O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-lrhamnopyranosyl)-(1→9)-oxynonanoyl-bovine serum albumin-the leprosy-specific, natural disaccharide-octyl-neoglycoprotein

Delphi Chatterjee, Sangnae Cho, Patrick J. Brennan, Gerald O. Aspinall

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Abstract

The outer disaccharide segment, namely O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-diO-methyl-α-l-rhamnopyranose, of the trisaccharide-containing, leprosy-specific, phenolic glycolipid I has been synthesized as the 8-(methoxycarbonyl)octyl glycoside in high yield and absolute stereospecificity by a series of modified Koenigs-Knorr and Helferich reactions. A particular feature of the synthetic pathway involves methylation of the 2-hydroxyl group of the rhamnose moiety under neutral conditions, after first preparing the 8-(methoxycarbonyl)octyl glycoside as the α anomer via the 1,2-orthoacetate, and thus precluding the possible formation of an anomeric mixture. The 8-(methoxycarbonyl)octyl O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-di-O-methyl-α-l-rhamnopyranoside was converted into the crystalline hydrazide, and this was coupled to bovine serum albumin (BSA), via intermediate acyl-azide formation, to produce the corresponding neoglycoprotein, O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-l-rhamnopyranosyl)-(1→9)-oxynonanoyl-BSA, the so-called natural disaccharide-octyl-BSA. Extensive serological testing of this product against sera from leprosy patients and control populations, and comparison with the native glycolipid and previously synthesized neoglycoproteins, have shown that it is unparalleled in terms of sensitivity and specificity, and highly suited to replace the native glycolipid for the serodiagnosis of worldwide lepromatous leprosy.

Original languageEnglish
Pages (from-to)39-56
Number of pages18
JournalCarbohydrate Research
Volume156
Issue numberC
DOIs
Publication statusPublished - 1986 Nov 15

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Glycolipids
Bovine Serum Albumin
Disaccharides
Leprosy
Glycosides
Glycoproteins
Lepromatous Leprosy
Trisaccharides
Rhamnose
Methylation
Azides
Serologic Tests
Hydroxyl Radical
Crystalline materials
Sensitivity and Specificity
Testing
Serum
Population
O-(3,6-di-O-methylglucopyranosyl)-(1-4)-O-(2,3-di-O-methylrhamnopyranosyl)-(1-9)-oxynonanoyl-bovine serum albumin

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

Cite this

@article{488863774d9e470f994980c4fdce1299,
title = "Chemical synthesis and seroreactivity of O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-lrhamnopyranosyl)-(1→9)-oxynonanoyl-bovine serum albumin-the leprosy-specific, natural disaccharide-octyl-neoglycoprotein",
abstract = "The outer disaccharide segment, namely O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-diO-methyl-α-l-rhamnopyranose, of the trisaccharide-containing, leprosy-specific, phenolic glycolipid I has been synthesized as the 8-(methoxycarbonyl)octyl glycoside in high yield and absolute stereospecificity by a series of modified Koenigs-Knorr and Helferich reactions. A particular feature of the synthetic pathway involves methylation of the 2-hydroxyl group of the rhamnose moiety under neutral conditions, after first preparing the 8-(methoxycarbonyl)octyl glycoside as the α anomer via the 1,2-orthoacetate, and thus precluding the possible formation of an anomeric mixture. The 8-(methoxycarbonyl)octyl O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-di-O-methyl-α-l-rhamnopyranoside was converted into the crystalline hydrazide, and this was coupled to bovine serum albumin (BSA), via intermediate acyl-azide formation, to produce the corresponding neoglycoprotein, O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-l-rhamnopyranosyl)-(1→9)-oxynonanoyl-BSA, the so-called natural disaccharide-octyl-BSA. Extensive serological testing of this product against sera from leprosy patients and control populations, and comparison with the native glycolipid and previously synthesized neoglycoproteins, have shown that it is unparalleled in terms of sensitivity and specificity, and highly suited to replace the native glycolipid for the serodiagnosis of worldwide lepromatous leprosy.",
author = "Delphi Chatterjee and Sangnae Cho and Brennan, {Patrick J.} and Aspinall, {Gerald O.}",
year = "1986",
month = "11",
day = "15",
doi = "10.1016/S0008-6215(00)90098-3",
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journal = "Carbohydrate Research",
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TY - JOUR

T1 - Chemical synthesis and seroreactivity of O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-lrhamnopyranosyl)-(1→9)-oxynonanoyl-bovine serum albumin-the leprosy-specific, natural disaccharide-octyl-neoglycoprotein

AU - Chatterjee, Delphi

AU - Cho, Sangnae

AU - Brennan, Patrick J.

AU - Aspinall, Gerald O.

PY - 1986/11/15

Y1 - 1986/11/15

N2 - The outer disaccharide segment, namely O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-diO-methyl-α-l-rhamnopyranose, of the trisaccharide-containing, leprosy-specific, phenolic glycolipid I has been synthesized as the 8-(methoxycarbonyl)octyl glycoside in high yield and absolute stereospecificity by a series of modified Koenigs-Knorr and Helferich reactions. A particular feature of the synthetic pathway involves methylation of the 2-hydroxyl group of the rhamnose moiety under neutral conditions, after first preparing the 8-(methoxycarbonyl)octyl glycoside as the α anomer via the 1,2-orthoacetate, and thus precluding the possible formation of an anomeric mixture. The 8-(methoxycarbonyl)octyl O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-di-O-methyl-α-l-rhamnopyranoside was converted into the crystalline hydrazide, and this was coupled to bovine serum albumin (BSA), via intermediate acyl-azide formation, to produce the corresponding neoglycoprotein, O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-l-rhamnopyranosyl)-(1→9)-oxynonanoyl-BSA, the so-called natural disaccharide-octyl-BSA. Extensive serological testing of this product against sera from leprosy patients and control populations, and comparison with the native glycolipid and previously synthesized neoglycoproteins, have shown that it is unparalleled in terms of sensitivity and specificity, and highly suited to replace the native glycolipid for the serodiagnosis of worldwide lepromatous leprosy.

AB - The outer disaccharide segment, namely O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-diO-methyl-α-l-rhamnopyranose, of the trisaccharide-containing, leprosy-specific, phenolic glycolipid I has been synthesized as the 8-(methoxycarbonyl)octyl glycoside in high yield and absolute stereospecificity by a series of modified Koenigs-Knorr and Helferich reactions. A particular feature of the synthetic pathway involves methylation of the 2-hydroxyl group of the rhamnose moiety under neutral conditions, after first preparing the 8-(methoxycarbonyl)octyl glycoside as the α anomer via the 1,2-orthoacetate, and thus precluding the possible formation of an anomeric mixture. The 8-(methoxycarbonyl)octyl O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-2,3-di-O-methyl-α-l-rhamnopyranoside was converted into the crystalline hydrazide, and this was coupled to bovine serum albumin (BSA), via intermediate acyl-azide formation, to produce the corresponding neoglycoprotein, O-(3,6-di-O-methyl-β-d-glucopyranosyl)-(1→4)-O-(2,3-di-O-methyl-α-l-rhamnopyranosyl)-(1→9)-oxynonanoyl-BSA, the so-called natural disaccharide-octyl-BSA. Extensive serological testing of this product against sera from leprosy patients and control populations, and comparison with the native glycolipid and previously synthesized neoglycoproteins, have shown that it is unparalleled in terms of sensitivity and specificity, and highly suited to replace the native glycolipid for the serodiagnosis of worldwide lepromatous leprosy.

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