Jenkins D J, Potter B V
Department of Medicinal Chemistry, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Somerset, UK.
Carbohydr Res. 1996 Jun 21;287(2):169-82. doi: 10.1016/0008-6215(96)00078-x.
Two routes to a glucose-based mimic of the second messenger 1D-myo-inositol 1,4,5-trisphosphate related to adenophostin A are described. Fischer glycosidation of D-glucose with allyl alcohol in the presence of a strong cation-exchange resin gave a 7:3 alpha: beta-anomeric mixture of allyl glucopyranosides (5ab) from which the pure alpha anomer 5a was isolated by crystallisation. Treatment of 5ab with 1.05 equiv of dibutyltin oxide followed by 2.1 equiv of benzoyl chloride gave allyl 2,6-di-O-benzoyl-alpha-D-glucopyranoside, which was converted in 3 steps into allyl 2,6-di-O-benzyl-3,4-O-isopropylidene-alpha-D-glucopyranoside (4). Alternatively, treatment of 5a with 2.5 equiv of dibutyltin oxide followed by benzyl bromide gave allyl 2,6-di-O-benzyl-alpha-D-glucopyranoside (9) which was also converted into 4. Compound 4 was elaborated to the phosphorylation precursor 2-hydroxyethyl 2,6-di-O-benzyl-alpha-D-glucopyranoside (12) in a convenient one-pot reaction, and 12 was phosphorylated and deblocked to afford 2-hydroxyethyl alpha-D-glucopyranoside 2',3,4-trisphosphate. The 2,6-di-O-benzyl derivative 9 was converted in high yield into 2,6-di-O-benzyl-3,4-di-O-(p-methoxybenzyl)-D-glucopyranose, a useful intermediate for the synthesis of adenophostin A and related compounds.
描述了两条合成基于葡萄糖的第二信使1D-肌醇1,4,5-三磷酸类似物的路线，该类似物与腺嘌呤宿主素A相关。在强阳离子交换树脂存在下，D-葡萄糖与烯丙醇进行费歇尔糖苷化反应，得到烯丙基吡喃葡萄糖苷（5ab）的α:β异头物混合物，比例为7:3，通过结晶分离出纯α异头物5a。用1.05当量的二丁基氧化锡处理5ab，然后用2.1当量的苯甲酰氯处理，得到烯丙基2,6-二-O-苯甲酰基-α-D-吡喃葡萄糖苷，该化合物经三步反应转化为烯丙基2,6-二-O-苄基-3,4-O-异亚丙基-α-D-吡喃葡萄糖苷（4）。或者，用2.5当量的二丁基氧化锡处理5a，然后用苄基溴处理，得到烯丙基2,6-二-O-苄基-α-D-吡喃葡萄糖苷（9），其也被转化为4。化合物4通过一个简便的一锅法反应被转化为磷酸化前体2-羟乙基2,6-二-O-苄基-α-D-吡喃葡萄糖苷（12），12经磷酸化和脱保护得到2-羟乙基α-D-吡喃葡萄糖苷2',3,4-三磷酸。2,6-二-O-苄基衍生物9以高产率转化为2,6-二-O-苄基-3,4-二-O-（对甲氧基苄基）-D-吡喃葡萄糖，这是合成腺嘌呤宿主素A及相关化合物的有用中间体。
