Abstract
GM1 is a common ganglioside pentasaccharide present on mammalian cell surface. It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation. In order to synthesize GM1, an efficient synthetic route was developed via a [3+2] strategy. The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor, which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone. The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups. Donor bearing the more rigid benzylidene group gave low glycosylation yield. Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide. Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain, which will be a valuable probe for biological studies.
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References
Hakomori S. Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Ann Rev Biochem, 1981, 50: 733–764
Hakomori S. Bifunctional role of glycosphingolipids. J Biol Chem, 1990, 265: 18713–18716
Imundo L, Barasch J, Prince A, Al-Awqati Q. Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface. Proc Natl Acad Sci USA, 1995, 92: 3019–3023
Bremer EG, Hakomori S, Bowen-Pope DF, Raines E, Ross R. Ganglioside-mediated modulation of cell growth, growth factor binding, and receptor phosphorylation. J Biol Chem, 1983, 259: 6818–6825
Rabin SJ, Mocchetti I. GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem, 1995, 65: 347–354
Ikeda K, Yamaguchi T, Fukunaga S, Hoshino M, Matsuzaki K. Mechanism of amyloid β-protein aggregation mediated by GM1 ganglioside clusters. Biochemistry, 2011, 50: 6433–6440
Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Maruyama W, Michikawa M, Yanagisawa K. A ganglioside-induced toxic soluble Aβ assembly. J Biol Chem, 2007, 282: 2646–2655
Williamson MP, Suzuki Y, Bourne NT, Asakura T. Binding of amyloid β-peptide to ganglioside micelles is dependent on histidine-13. Biochem J, 2006, 397: 483–490
Hayashi H, Kimura N, Yamaguchi H, Hasegawa K, Yokoseki T, Shitaba M, Yamamoto N, Michikawa M, Yoshikawa Y, Terao K, Matsuzaki K, Lemere CA, Selkoe DJ, Naiki H, Yanagisawa K. A seed for alzheimer amyloid in the brain. J Neurochem, 2004, 24: 4894–4902
Choo-Smith LP, Garzon-Rodriguez W, Glabe CG, Surewicz WK. Acceleration of amyloid fibril formation by specific binding of Aβ-(1–40) peptide to ganglioside-containing membrane vesicles. J Biol Chem, 1997, 272: 22987–22990
Gylys KH, Fein JA, Yang F, Miller CA, Cole GM. Increased cholesterol in Aβ-positive nerve terminals from Alzheimer's disease cortex. Neurobiol Aging, 2007, 28: 8–17
Komori T, Imamura A, Ando H, Ishida H, Kiso M. Study on systematizing the synthesis of the β-series ganglioside glycans GT1a, GD1a, and GM1 using the newly developed N-Troc-protected GM3 and GalN intermediates. Carbohydrate Res, 2009, 344: 1453–1463
Cheshev PE, Khatuntseva EA, Tsvetkov YE, Shashkov AS, Nifantiev NE. Synthesis of aminoethyl glycosides of the ganglioside GM(1) and asialo-GM(1) oligosaccharide chains. Russ J Bioorg Chem, 2004, 30: 60–70
Bhattacharya SK, Danishefsky SJ. A total synthesis of the methyl glycoside of ganglioside GM1. J Org Chem, 2000, 65: 144–151
Stauch T, Greilich U, Schmidt RR. Glycosyl Imidates, 73. Synthesis of ganglioside GM1 via a GA1 intermediate. Liebigs Ann, 1995: 2101–2111
Hasegawa A, Nagahama T, Kiso M. A facile, systematic synthesis of ganglio-series gangliosides: Total synthesis of gangliosides GM1 and GD1a. Carbohydr Res, 1992, 235: C13–C17
Sugimoto M, Numata M, Koike K, Nakahara Y, Ogawa T. Total synthesis of gangliosides GM1 and GM2. Carbohydr Res, 1986, 156: C1–C5
Ye X-S, Huang X, Wong CH. Conversion of the carboxy group of sialic acid donors to a protected hydroxymethyl group yields an efficient reagent for the synthesis of the unnatural beta-linkage. Chem Commun, 2001: 974–975
Boons G-J, Demchenko AV. Recent advances in O-sialylation. Chem Rev, 2000, 100: 4539–4565
Sun B, Pukin A, Visser GM, Zuilhof H. An efficient glycosylation reaction for the synthesis of asialo GM2 analogues. Tetrahedron Lett, 2006, 47: 7371–7374
Demchenko AV, Boons G-J. A highly convergent synthesis of a complex oligosaccharide derived from group B type III streptococcus. J Org Chem, 2001, 66: 2547–2554
Wang YJ, Jia J, Gu ZY, Liang FF, Li RC, Huang MH, Xu CS, Zhang JX, Men Y, Xing GW. Tunable stereoselectivity during sialylation using an N-acetyl-5-N,4-O-oxazolidinone-protected p-toluene 2-thiosialoside donor with Tf(2)O/Ph(2)SO/TTBPy. Carbohydr Res, 2011, 346: 1271–1276 and references cited therein
Crich D, Wu B. Imposing the trans/gauche conformation on a sialic acid donor with a 5-N,7-O-oxazinanone group: Effect on glycosylation stereoselectivity. Tetrahedron, 2008, 64: 2042–2047 and references cited therein
Sun B, Srinivasan B, Huang X. Pre-activation based one-pot synthesis of an α-(2,3)-sialylated core-fucosylated complex type Bi-antennary N-Glycan dodecasaccharide. Chem Eur J, 2008, 14: 7072–7081
Crich D, Wu B. Stereoselective iterative one-pot synthesis of N-glycolylneuraminic acid-containing oligosaccharides. Org Lett, 2008, 10: 4022–4035
Wang Z, Zhou L, El-boubbou K, Ye X-S, Huang X. Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen globo-H based on preactivation of thioglycosyl donors. J Org Chem, 2007, 72: 6409–6420
Huang X, Huang L, Wang H, Ye X-S. Iterative one-pot synthesis of oligosaccharides. Angew Chem Int Ed, 2004, 43: 5221–5224
Wang Z, Xu Y, Yang B, Tiruchinapally G, Sun B, Liu R, Dulaney S, Liu J, Huang X. Preactivation-based, one-pot combinatorial synthesis of heparin-like hexasaccharides for the analysis of heparin-protein interactions. Chem Eur J, 2010, 16: 8365–8375 and references cited therein
Koeller KM, Wong C-H. Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. Chem Rev, 2000, 100: 4465–4493
References
Wang Z, Zhou L, El-boubbou K, Ye X-S, Huang X. Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen globo-H based on preactivation of thioglycosyl donors. J Org Chem, 2007, 72: 6409–6420
Demchenko AV, Boons G-J. A highly convergent synthesis of a complex oligosaccharide derived from group B type III streptococcus. J Org Chem, 2001, 66: 2547–2554
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Sun, B., Yang, B. & Huang, X. Total synthesis of the aminopropyl functionalized ganglioside GM1 . Sci. China Chem. 55, 31–35 (2012). https://doi.org/10.1007/s11426-011-4449-x
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DOI: https://doi.org/10.1007/s11426-011-4449-x