Muscular dystrophy is an inherited disorder that shows symptoms of muscle fiber necrosis or degeneration. Dystroglycan (DG) is a glycoprotein found in skeletal muscle and is a component of the dystrophin-glycoprotein complex. DG plays a role to connect dystrophin and laminin, which is a component of extracellular matrix, through O-mannosyl glycan (MG).This dystrophin-glycoprotein complex mediated basement membrane-cytoskeleton linkage is important for maintaining the strength of muscle cell membranes that can withstand muscle contraction and mechanical stress.It is thought that the muscular dystrophy develops due to the failure of this connection. Glycan substrate having a partial structure of O-MG is required to elucidate the detailed biosynthetic mechanism of O-MG. However, the enzymatic synthesis of the partial structure of O-MG could give limited compounds. To find the primers for enzymatic glycan elongation, the partial structures of O-MG (1-3) containing xylose(Xyl)-Rbo5P have been synthesized. Suitably protected Rbo compound masked with TBDPS at O-5 was prepared, to which was coupled a xlyosyl chloride in the presence of AgOTf and collidine in (CH2Cl)2to give the β-linked Xyl-Rbo. All the protecting groups were removed to give the desired Xylβ1-4Rbo(1). Deprotection after phosphorylation at O-5 of protected Xyl-Rbo afforded 2. Xylβ1-4Rbo5-P-1Rbo (3) was also obtained by the coupling of phosphoramidite of Rbo with protected Xyl-Rbo. We succeeded the regio- and stereoselective synthesis of O-MG (1-3). The results of 1H and 13C NMR measurements of compounds 2and 3agreed with those previously reported.

Synthesis of xylosyl ribitol phosphate

2019 Fall National Meeting

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