Formaldehyde → 2,5-Anhydro-2-C-(hydroxymethyl)-3,4,6-tris-O-(phenylmethyl)-D-arabino-hexitol
反応式
[C:1]1([CH2:7][O:8][C@H:9]2[C@H:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:14]([CH2:24][O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:13][C@@H:10]2[CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:35](=O)([O-])[O-:36].[K+].[K+]>CO>[OH:12][CH2:11][C:10]1([O:13][C@H:14]([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:9]1[O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:35][OH:36]参加物
5
実験手順
In accordance with Flowchart F, 2,5-anhydro--3,4,6-tris-O-(phenylmethyl)-D-mannose 4 is treated with 37% formalin and potassium carbonate in methanol at 85° C., then neutralized, giving 2,5-anhydro-2-C-(hydroxymethyl)-3,4,6-tris-O-(phenylmethyl)-D-arabinohexitol 46, which is reacted with benzaldehyde dimethyl acetal and p-toluenesulfonic acid in dimethylformamide at 60° C., giving 2,5-anhydro-2-C-(hydroxymethyl)-3,4,6--tris-O-(phenylmethyl)-1,21 -O-(phenylmethylene)-[R(or S)]-glucitol 47. Compound 47 is reacted with lithium aluminum hydride and aluminum chloride in dichloromethane: ether (1:1) at 45°-50° C., then flash chromatographed to separate the desired glucitol compound 48, which is reacted with oxalyl chloride in dimethyl sulfoxide and dichloromethane under argon at -60° C. followed by treatment with triethylamine and water, giving 2,5-anhydro-2-C-[(phenylmethoxy)methyl]-3,4,6-tris-O--(phenylmethyl)-D-glucose 49. Compound 49 is dissolved in diethyl phosphite, treated with triethylamine under argon, then with acetic acid, giving [1R(and 1S)]-2,5-anhydro-1-C-(diethoxyphosphinyl)-2-C-[(phenylmethoxy) methyl]-3,4,6-tris-O-(phenylmethyl)-D-glucitol 50 and 51, which are separated by chromatography. The major, less polar isomer of 50 and 51 (not identified) is treated with diethylamino sulfur trifluoride in dry dichloromethane, followed by saturated sodium bicarbonate, giving [1R(or 1S)]-2,5-anhydro-1-deoxy-1-(diethoxyphosphinyl)-1-fluoro-2-C-[(phenylmethoxy)-methyl]-3,4,6-tris-O-(phenylmethyl)-D-glucitol 52. Compound 52 is treated with boron trifluoride etherate in acetic anhydride at 0° C. under argon, followed by sodium bicarbonate, giving 2,5-anhydro-1-deoxy-1-(diethoxyphosphinyl)-1-fluoro-2-C-[(phenylmethoxy)methyl]-3,4-bis-0-(phenylmethyl)-D-glucitol, acetate 53 which is treated with sodium ethoxide in ethanol under argon followed by acetic acid, giving 2,5-anhydro-1-deoxy-1-(diethoxyphosphinyl)-1-fluoro-2-C-[(phenylmethoxy) methyl]-3,4-bis-O-(phenylmethyl)-D-glucitol 54. Compound 54 is treated with diphenyl chlorophosphate in cold pyridine, giving [1R(or 1S)]-2,5-anhydro-1-deoxy-1-(diethoxyphosphinyl)-1-fluoro-2-C-[(phenylmethoxy)methyl]-3,4-bis-O-(phenylmethyl)-D-glucitol, diphenyl phosphate 55 which is treated with trimethylsilyl bromide in deuterated chloroform under argon, followed by sequential hydrogenation, first over palladium-on-carbon, then platinum oxide, both in methanol, to obtain the desired product 2,5-anhydro--1-deoxy-1-fluoro-2-(hydroxymethyl)-1-phosphono-D-glucitol, 6-(dihydrogen phosphate) 56. ##STR15##