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DOI: 10.1055/s-2008-1078249
Synthesis of Mucin Glycans from the Protozoon Parasite Trypanosoma cruzi
Publication History
Publication Date:
05 August 2008 (online)
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Abstract
A short, blockwise, 2+2-glycosylation approach to the synthesis of a tetrasaccharide component of Trypanosoma cruzi mucin is reported. Despite the use of a 1,2-linked disaccharide donor, high yield (79%) and good stereocontrol (>10:1, β:α) were achieved in the key glycosylation step. Preliminary studies indicate that this branched tetrasaccharide can serve as a substrate for enzymatic sialylation by the parasite cell surface trans-sialidase.
Key words
oligosaccharide - synthesis - parasite - mucin - trans-sialidase - drug target
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References and Notes
http://www.who.int/topics/chagas_disease/en/.
![](https://www.thieme-connect.de/media/synlett/200814/d194_s3.gif)
Scheme 3 Action of recombinant T. cruzi trans-sialidase on synthetic mucin tetrasaccharide 1. [7d]
The studies reported herein have been conducted in parallel with efforts that replace the reducing terminal N-acetyl-glucosamine unit with mannose, which offers more straightforward entry to an α-linked amino acid-glycan linkage.
22In the parallel series with a mannose
at the reducing terminus, the corresponding coupling gave complete
β-stereocontrol
albeit in lower yield (54%).
Selected Analytical
Data
Imidate 3: [α]D
²0 +41.0
(c 1, CHCl3). ¹H
NMR (400MHz, CDCl3): δ = 8.65 (s, 1
H, NH), 6.51 (d, 1 H, H1, J
1,2 = 3.6 Hz),
4.66 (d,1 H, H1′, J
1
′
,2
′ = 7.8
Hz). ¹³C NMR (100 MHz, CDCl3): δ = 160.7
(C=NH), 101.3 (C1′), 94.9 (C1). HRMS: m/z calcd for C28O18NCl3H36 [M + NH4]:
797.1336; found: 797.1339.
Tetrasaccharide 5: [α]D
²0 -4.0
(c 1 in CHCl3). ¹H
NMR (600 MHz, CDCl3): δ = 4.78 (d,
1 H, H1c, J
1,2 = 8.0
Hz), 4.70 (d, 1 H, H1a, J
1,2 = 10.0
Hz), 4.60 (d, 1 H, H1b, J
1,2 = 7.7
Hz), 4.55 (d, 1 H, H1d, J
1,2 = 7.9
Hz). ¹³C NMR (100 MHz, CDCl3): δ = 101.7
(C1b), 100.9 (C1c), 100.3 (C1d), 85.5 (C1a). MS (ES): m/z = 1372.5 [M + Na]+.
Tetrasaccharide 1: [α]D
²0 +15.0
(c 1 in H2O). ¹H
NMR, (400 MHz, D2O): δ = 4.87 (d, 1
H, H1a, J
1,2 = 10.4
Hz), 4.37 (d, 1 H, H1b, J
1,2 = 6.8
Hz), 4.34 (d, 1 H, H1c, J
1,2 = 8.0
Hz), 4.31 (d, 1 H, H1d, J
1,2 = 7.9
Hz). ¹³C NMR (75 MHz, D2O): δ = 175.1
(C=ONHAc), 104.2 (C1c), 103.8 (C1d), 102.2 (C1b), 85.9
(C1a). HRMS: m/z calcd for C32H49N3O20S [M + Na]+:
822.2461; found: 822.2487.