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【结 构 式】

【分子编号】48950

【品名】(3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate

【CA登记号】

【 分 子 式 】C31H32Cl3NO9

【 分 子 量 】668.95452

【元素组成】C 55.66% H 4.82% Cl 15.9% N 2.09% O 21.53%

与该中间体有关的原料药合成路线共 4 条

合成路线1

该中间体在本合成路线中的序号:(XVIII)

Synthesis of intermediate monosaccharide (XVIII): The reaction of tetraacetyl-D-xylose (IX) with HBr in HOAc gives the bromoglycoside (X), which by reaction with ethylmercaptane and lutidine yields the thio orthoester (XI). Hydrolysis of (XI) with NaOMe in methanol affords the deacetylated compound (XII), which is protected with Pmb-Cl and NaH to provide the diether (XIII). The cleavage of the cyclic thio orthoester with ZnCl2 in dichloromethane gives the 2-O-acetyl-thioglycoside (XIV), which is hydrolyzed with NaOMe in methanol to yield the alcohol (XV). Esterification of (XV) with 4-methoxybenzoyl chloride (XVI), DMAP and TEA affords the benzoate ester (XVII), which is finally converted into the target acetimidate (XVIII) by reaction with NBS in dichloromethane/water, and then with trichloroacetonitrile and DBU in the same solvent.

1 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 48943 (3R,4S,5R)-2,3,5-tris(acetoxy)tetrahydro-2H-pyran-4-yl acetate C13H18O9 详情 详情
(X) 23761 (2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate C11H15BrO7 详情 详情
(XI) 48944 (2S,3aR,6R,7S,7aR)-6-(acetoxy)-2-(ethylsulfanyl)-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl acetate C13H20O7S 详情 详情
(XII) 48945 (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-6,7-diol C9H16O5S 详情 详情
(XIII) 48946 (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-6-[(4-methoxybenzyl)oxy]-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl 4-methoxybenzyl ether; (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-6,7-bis[(4-methoxybenzyl)oxy]-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran C25H32O7S 详情 详情
(XIV) 48947 (2R,3R,4S,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl acetate C25H32O7S 详情 详情
(XV) 48948 (2S,3R,4R,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-ol C23H30O6S 详情 详情
(XVI) 22671 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride 100-07-2 C8H7ClO2 详情 详情
(XVII) 48949 (2S,3R,4S,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H36O8S 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XVIII)

Synthesis of intermediate disaccharide (XX): The condensation of intermediate monosaccharide (VIII) with intermediate acetimidate (XVIII) by means of BF3/Et2O gives the disaccharide (XIX), which is converted into the desired acetimidate (XX) by reaction with NBS and trichloroacetonitrile and DBU in dichloromethane/water.

1 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情
(XIX) 48951 (2S,3R,4S,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C48H60O13SSi 详情 详情
(XX) 48952 (2S,3R,4S,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情

合成路线3

该中间体在本合成路线中的序号:(XVIII)

D-xylose trichloroacetimidate intermediate (XVIII): The reaction of tetraacetyl-D-xylose (IX) with HBr/AcOH n dichloromethane gives the glycosyl bromide (X), which is treated with Et-SH and lutidine in nitromethane to yield the thio orthoester (XI). The deacetylation of (XI) by means of NaOMe in methanol affords dihydroxy compound (XII), whose OH groups are protected by means of Pmb-Cl and NaH to provide the bis 4-methoxybenzyl ether compound (XIII). ZnCl2 promoted ring opening of the thio orthoester group of (XIII) leads to the thioglycoside (XIV), which is deacetylated by means of NaOMe in methanol to give compound (XV). The acylation of the free OH group of (XV) with 4-methoxybenzoyl chloride (XVI), TEA and DMAP in dichloromethane yields the benzoate ester (XVII), which is finally converted into the target D-xylose trichloroacetimidate (XVIII) by reaction with NBS, Cl3C-CN and DBU in dichloromethane

1 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 48936 D-Arabinose tetraacetate C13H18O9 详情 详情
(X) 23761 (2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate C11H15BrO7 详情 详情
(XI) 60144 (2S,3aR,6R,7S,7aR)-6-(acetyloxy)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl acetate C14H22O7S 详情 详情
(XII) 60145 (2S,3aR,6R,7S,7aR)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-6,7-diol C10H18O5S 详情 详情
(XIII) 60146 (2S,3aR,6R,7S,7aR)-6,7-bis[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran; (2S,3aR,6R,7S,7aR)-6-[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl 4-methoxybenzyl ether C26H34O7S 详情 详情
(XIV) 60147 (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl acetate C26H34O7S 详情 详情
(XV) 60149 (2S,3R,4R,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-ol C24H32O6S 详情 详情
(XVI) 60148 4-methoxybenzoic acid C8H8O3 详情 详情
(XVII) 60150 (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C32H38O8S 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情

合成路线4

该中间体在本合成路线中的序号:(XVIII)

Intermediate beta-disaccharide trichloroacetimidate (XX): The glycosylation of intermediate (VIII) with intermediate (XVIII) by means of BF3/Et2O in dichloromethane gives the beta-disaccharide (XIX), which is converted into the target trichloroacetimidate (XX) by reaction with NBS, Cl3C-CN and DBU in dichloromethane

1 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情
(XIX) 48951 (2S,3R,4S,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C48H60O13SSi 详情 详情
(XX) 60151 (2S,3R,4S,5R)-2-({(2S,3R,4R,5S)-3-(acetyloxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl}oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情
Extended Information