【结 构 式】 |
【药物名称】SKK-60060 【化学名称】2-Tetradecylhexadecyl 2-O-(3-O-sulfo-6-deoxy-alpha-L-galactopyranosyl)-3-O-sulfo-beta-D-galactopyranoside disodium salt 【CA登记号】190443-07-3 【 分 子 式 】C42H80Na2O16S2 【 分 子 量 】951.2039 |
【开发单位】Sanwa (Originator) 【药理作用】OCULAR MEDICATIONS, Ophthalmic Drugs, Other Ocular Medications, Retinoprotectors, Selectin Inhibitors |
合成路线1
Treatment of 2-(tetradecyl)hexadecyl beta-D-galactopyranoside (I) with benzaldehyde dimethyl acetal (II) in THF containing H2SO4 provides 4,6-O-benzylidene derivative (III), which is then subjected to 3-O-4-methoxybenzylation by reaction with 4-methoxybenzyl chloride (IV), dibutyltin oxide (Bu2SnO) and tetrabutyl ammonium iodide (Bu4NI) in THF to furnish compound (V). On the other hand, phenyl 1-thio-beta-L-fucopyranoside (VI) is regioselectively protected with chloride (IV) by means of dibutyl oxide and tetrabutyl ammonium iodide in THF/MeOH to yield derivative (VII), which is benzylated by means of benzyl bromide (BnBr) and NaH in DMF to give fucopyranoside derivative (VIII). Glycosylation of compound (V) with derivative (VIII) is then performed in the presence of N-iodosuccinimide (NIS), trifluoromethanesulfonic acid (TfOH) and molecular sieves in toluene to afford disaccharide (IX), whose 4-methoxybenzyl groups are removed in CH2Cl2/H2O in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to yield (X). Sulfation of compound (X) with SO3.pyridine complex in DMF provides sulfate (XI), which is finally hydrogenated over Pd/C in MeOH/THF to furnish the desired product.
【1】 Ikami, T.; et al.; Synthetic studies on selectin ligands/inhibitors: Synthesis and inhibitory activity of 2-O-fucosyl sulfatides containing 2-branched fatty alkyl residues in place of ceramide. J Carbohydr Chem 1998, 17, 3, 453. |
【2】 Usui, T.; Igami, T.; Kakigami, T.; Hamashima, H.; Jomori, T.; Tashita, A.; Ishiwatari, Y.; Yokochi, S.; Mitani, T.; Suzuki, Y.; Hasegawa, A. (Sanwa Kagaku Kenkyusho Co., Ltd.); Sulfated and phosphated saccharide derivs., process for the preparation of the same and use thereof. EP 0771815; JP 1997183789; US 5869460 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 45977 | (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-[(2-tetradecylhexadecyl)oxy]tetrahydro-2H-pyran-3,4,5-triol | C36H72O6 | 详情 | 详情 | |
(II) | 27515 | Methoxy(phenyl)methyl methyl ether; Dimethylacetal benzaldehyde; Benzaldehyde dimethylacetal | 1125-88-8 | C9H12O2 | 详情 | 详情 |
(III) | 45978 | (4aR,6R,7R,8R,8aR)-2-phenyl-6-[(2-tetradecylhexadecyl)oxy]hexahydropyrano[3,2-d][1,3]dioxine-7,8-diol | C43H76O6 | 详情 | 详情 | |
(IV) | 11910 | 4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether | 824-94-2 | C8H9ClO | 详情 | 详情 |
(V) | 45979 | (4aR,6R,7R,8R,8aR)-8-[(4-methoxybenzyl)oxy]-2-phenyl-6-[(2-tetradecylhexadecyl)oxy]hexahydropyrano[3,2-d][1,3]dioxin-7-ol | C51H84O7 | 详情 | 详情 | |
(VI) | 45980 | (2S,3S,4R,5S,6R)-2-methyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol | C12H16O4S | 详情 | 详情 | |
(VII) | 45981 | (2S,3S,4R,5S,6R)-4-[(4-methoxybenzyl)oxy]-2-methyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-3,5-diol | C20H24O5S | 详情 | 详情 | |
(VIII) | 45982 | (2S,3S,4R,5S,6R)-3,5-bis(benzyloxy)-4-[(4-methoxybenzyl)oxy]-2-methyl-6-(phenylsulfanyl)tetrahydro-2H-pyran; benzyl (2R,3S,4R,5S,6S)-5-(benzyloxy)-4-[(4-methoxybenzyl)oxy]-6-methyl-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl ether | C34H36O5S | 详情 | 详情 | |
(IX) | 45985 | (4aR,6R,7R,8S,8aR)-7-([(2S,3S,4R,5S,6S)-3,5-bis(benzyloxy)-4-[(4-methoxybenzyl)oxy]-6-methyltetrahydro-2H-pyran-2-yl]oxy)-8-[(4-methoxybenzyl)oxy]-2-phenyl-6-[(2-tetradecylhexadecyl)oxy]hexahydropyrano[3,2-d][1,3]dioxine; (4aR,6R,7R,8S,8aR)-7-([(2S,3S,4R,5S,6S)-3,5-bis(benzyloxy)-4-[(4-methoxybenzyl)oxy]-6-methyltetrahydro-2H-pyran-2-yl]oxy)-8-[(4-methoxybenzyl)oxy]-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl 2-tetradecylhexadecyl ether | C79H114O12 | 详情 | 详情 | |
(X) | 45983 | (4aR,6R,7R,8S,8aR)-7-[[(2S,3S,4R,5S,6S)-3,5-bis(benzyloxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-2-phenyl-6-[(2-tetradecylhexadecyl)oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-ol | C63H98O10 | 详情 | 详情 | |
(XI) | 45984 | C64H98Na2O15S2 | 详情 | 详情 |