Synthesis of Fluorogenic Substrates for Detection of a-L-Iduronidase Deficiency in Mucopolysaccharidosis

• Main Authors: Chien-Sheng Chen, 陳建盛
• Other Authors: Chun-Chen Liao
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/89807915819551463990

碩士 === 國立清華大學 === 化學系 === 88 === A novel and efficient route toward the formal synthesis of 4-methylcoumarin-7-yl α-L-idopyranosiduronic acid 1, a fluorogenic substrate for assay of α-L-iduronidase activity in Mucopolysaccharidosis, began with the b-L-idofuranoses 21 or 22, available from diacetone α-D-glucose 23 or 1,2-O-isoproplidene-α-D-glucofuranose 24 in four and three steps, respectively. Hydrolysis of 21 or 22 in acidic media at refluxing temperature led to 1,6-anhydroxy-β-L-idopyranose 19 in good yield. One-pot acetolysis and bromination provided 2,3,4,6-tetra-O-acetyl-L-idopyranose 18 (90%) which was coupled with 7-hydroxy-4-methylcoumarin 2 employing the Mitsunobu-type glycosylation to afford the adduct 36α in 58% yield. De-acetylation with sodium methoxide gave the target tetraol 11 (82%) which could be transformed into 1 in one step according to the known method.