Synthesis of gangliosides

The first total synthesis of sLex hexasaccharyl ceramide was reported by Akira Hasegawa s group in 1991 using thioglycoside donors, emphasizing on the utility 

SCHEME 12.14 Hasegawa s total synthesis of si.o hexasaccharide ceramide. 

SCHEME 12.15 Wong s one-pot assembly of sLex hexasaccharide. Phth, phthaloyl. 

A synthesis of two deoxy Lewis X pentaosyl GSLs is also reported [107]. Kyriacos Nicolaou [108], Samuel Danishefsky [109-111], and Khushi Matta [112] have reported the synthesis of the main sLex antigen. A fully automated enzymatic synthesis of sLex derivatives in 4 days and 16% overall yield from a simple GlcNac-linked aminooxy-functionalized G7 dendrimer is recently reported [113]. 

SCHEME 12.16 Seeberger s synthesis of the key sialo disaccharide. BAIB, [bis(acetoxy) iodo]benzene. 

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The exact role of ceramide in apoptosis seems not to be clear because of problems detecting ceramide levels (Kolesnick and Hannun, 1999 Hofmann and Dixit, 1999 Watts et al, 1999). Ganglioside GD3 is an important mediator of Fas-induced apoptosis in hematopoietic cells. Ceramide triggers the synthesis of ganglioside GD3 (DeMaria et al., 1997). So it is difficult to explain vdiether the inducer of apoptosis is ceramide or ganglioside. 

H. Ishida, Y. Ohta, Y. Tsukada, M. Kiso, and A. Hasegawa, A synthetic approach to polysialo-gangliosides containing a-sialyl-(2— 8) sialic acid Total synthesis of ganglioside GD3, Carbohydr. Res. 246 15 (1993). 

M. Kiso and A. Hasegawa, Synthesis of ganglioside GM and analogs containing modified sialic acids and ceramides, Methods Enzymol. 242 171 (1994). 

A. Hasegawa and M. Kiso, Systematic synthesis of gangliosides toward the elucidation and... 

A. Hasegawa, T. Nagahama, and M. Kiso, A facile, systematic synthesis of ganglio-series gangliosides Total synthesis of gangliosides GM, and GDla, Carbohydr. Res. 235 C 3 (1992). 

Keenan, T. W. 1974. Composition and synthesis of gangliosides in mammary gland and milk of the bovine. Biochim. Biophys. Acta 337, 255-270. 

In conclusion, we have successfully demonstrated the usefulness of a new approach for treatment of memory deficit by upregulating de novo synthesis of gangliosides and synaptic function by applying the synthetic ceramide analog. Our results summarized here open up the possibility of a new therapeutic strategy for neurodegenerative disorders. 

A bifunctional sialyltransferase Cst-II from C. jejuni OH4384 carrying both a2,3- and a2,8-sialyltransferase activities was used in the enzymatic synthesis of ganglioside mimic GD3 (66). 

Prabhanjan H, Ishida H, Kiso M, Hasegawa A. A facile total synthesis of ganglioside GMlb and its positional analog. Carbohydr Res 1991 211 Cl-5. 

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