(2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate -Drug Synthesis Database

【结构式】

【分子编号】23761

【品名】(2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate

【CA登记号】

【分子式】C₁₁H₁₅BrO₇

【分子量】339.1399

【元素组成】C 38.96% H 4.46% Br 23.56% O 33.02%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(X)

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.

参考文献中间体

合成目标

【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：(X)

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

参考文献中间体

合成目标

【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	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

Extended Information