Ceramide tetrasaccharide

Siddiqui, B. Hakomori, S. A ceramide tetrasaccharide of human erythrocyte membrane reacting of the anti-type. 

Siddiqui, B., Kawanami, J., lin, Y.T. Hakomori, S.I. (1972) Structure of Ceramide Tetrasaccharides from Various Sources Uniqueness of Rat Kidney Ceramide Tetrasaccharide , Journal of Lipid Research, 13, 657-62 Singer, S.J. Nicolson, G.L. (1972) The Fluid Mosaic Model of the Structure of Cell Membranes , Science (New York), 175, 720-31 Sinnott, M.L. Smith, P.J. (1976) Active-site-directed Irreversible Inhibition of E. coli P-galactosidase by the Hot Carbonium Ion Precursor, f-D-Galactopyronosylmethyl-p-nitrophenyltriazene . Journal of the Chemical Society, Chemical Communications, pp. 223-4... 

Whether such a block constitutes the only mechanism by which ganglioside accumulates in brain is by no means certain. In fact, reports have appeared claiming an accumulation of the ceramide tetrasaccharide complexes (A and C) in some cases of Tay-Sachs disease. Furthermore, the coexistence of Tay-Sachs disease and abnormal gangliosides cannot be excluded (see above). Brain lipoidosis, like glyco-genesis, could result from several different metabolic alterations. 

Dennis, R.D., Baumeister, S., Geyer, R., Peter-Katalinic, J., Hartmann, R., Egge, H., Geyer, E. and Wiegandt, H. (1992) Glycosphingolipids in cestodes - chemical structures of ceramide monosaccharide, disaccharide, trisaccharide and tetrasaccharide from metacestodes of the fox tapeworm, Taenia crassiceps (Cestoda Cyclophyllidea). European Journal of Biochemistry 207, 1 053-1 062. 

Ogawa and co-workers [97] have synthesised the complete glycosphingolipid (361) containing the terminal tetrasaccharide (356) of the Leb antigen attached to lactosyl ceramide. The lactose derivative (95), prepared by the action of trimethylamine — borane and aluminium chloride [99] on the benzylidene derivative (94), was condensed with the thioglucoside (362) in the presence of methyl triflate and molecular sieve to give the trisaccharide (363). This was deacetylated and the product (364) condensed... 

To simplify the nomenclature, the International Union of Pure and Applied Chemistry recommended abbreviations for the oligosaccharide chains of GSLs [9], The neutral core (root) structures, their symbols, and commonly used abbreviations are shown in Table 12.1. The name of a particular GSL is composed of (root name) (root size) osylceramide. Thus, the sixth structure in Table 12.1, if linked to ceramide, is named globotetraosylceramide, which could be abbreviated as Gb4Cer (the subscript 4 refers to the tetrasaccharide core). 

The Le tetrasaccharide determinant consists of a bis-fiicosylated 7V-acetyl lac-tosamine. We reasoned that the iodosulfonamidation methodology could be used to install the amine function and would favor the subsequent incorporation of additional glycal units. It also seemed likely that both the Le -ceramide target and the Le -conjugate could be prepared from a common, but late, glycal epoxide intermediate. 

Compound 152 was destined to house the lactose bearing the ceramide unit and was therefore converted to triol 155. While 155 has several potential glycosylation sites, in principle, the C3 hydroxyl is the most reactive position. A suitable donor could be fashioned by subjecting 153, the core of the Le sector, to IDCP iodo-sulfonamidation (see 156). Addition of ethanethiolate effected the roll over reaction and the donor was ready for coupling with 155. In the event, treatment of 157 with 155 under promotion of MeOTf did, in fact, give the desired tetrasaccharide 158, albeit often in low yield (35-55%). In addition, the reaction mixture appeared to contain significant quantities of at least one regioisomer. 

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