Synthesis glycosphingolipid

Platt, F. M. and Butters, T. D. Inhibition of substrate synthesis a pharmacological approach for glycosphingolipid storage disease therapy. In F. M. Platt and S. U. Walkley (eds), Lysosomal Disorders of the Brain. New York Oxford University Press, 2004, pp. 381 108. 

Cerebrosides are major constituents of the membrane of brain cells. They are the simplest glycosphingolipids, serving as model substances for more complex lipids of this kind. Furthermore, they are credited with important properties as receptors for hormones and toxins.29 Schemes 4 13 and 4 14 provide a method for preparing sphingosine and its analogs that can be used for the synthesis of cerebroside compounds. 

Sulfation of the carbohydrate chain occurs after the monosaccharide to be sulfated has been incorporated into the growing carbohydrate j chain. The source of the sulfate is 3 -phosphoadenosyl-5 -phospho-sulfate (PAPS, a molecule of AMP with a sulfate group attached to the 5-phosphate). Sulfotransferases cause the sulfation of the carbohydrate chain at specific sites. [Note An example of the synthesis of a sulfated glycosaminoglycan, chondroitin sulfate, is shown in Figure 14.11.] PAPS is also the sulfur donor in glycosphingolipid synthesis. [Note A defect in the sulfation process results in one of several autosomal recessive disorders that affect the proper development and maintenance of the skeletal system. This illustrates Ihe importance of the sulfation step.]... 

Synthesis of glycosphingolipids occurs in the endoplasmic reticului and Golgi by sequential addition of glycosyl monomers transferred fio sugar-nucleotide donors to the acceptor molecule. The mechanism similar to that used in glycoprotein synthesis (see p. 164). 

The enzymes involved in the synthesis of glycosphingolipids are cjh cosyl transferases, each specific for a particular sugar-nucleotid and acceptor. [Note These enzymes may recognize both glya sphingolipids and glycoproteins as substrates.]... 

Synthesis of a GalN3 (I-4)Gal Glycoside A Building Block for Glycosphingolipids of the Ganglio-Series [45]... 

Sphingomyelin Is Formed Directly from Ceramide Glycosphingolipid Synthesis Also Starts from Ceramide... 

Glycosphingolipid Synthesis Also Starts from Ceramide... 

Shapiro and co-workers have described [89] (in a paper submitted just before the death of this pioneer in the field of glycosphingolipid synthesis — for a review of his extensive work in this area see Ref. [1]) a synthesis of the thio-analogue (88) of glucosyl ceramide (and the saturated derivative) from 2,3,4,6-tetra-0-acetyl-l-mercapto- 3-D-glucopyranose (86) and the 1-deoxy-l-iodoceramide derivative (85) in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene. The product (87) was deacylated with methano-lic barium methoxide to give (88). 

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