Trolox; Trolox C; 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】21255

【品名】Trolox; Trolox C; 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylic acid

【CA登记号】53188-07-1

【分子式】C₁₄H₁₈O₄

【分子量】250.29452

【元素组成】C 67.18% H 7.25% O 25.57%

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：(XXII)

The esterification of (rac)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid (XXII) with diazomethane gives the methyl ester (XXIII), which is treated with Bn-Br and K2CO3 yielding the benzyl ether (XXIV). The reduction of the ester group of (XXIV) with LiAlH4 provides the carbinol (XXV), which is debenzylated with H2 over Pd/C to afford the racemic phenol (rac)-(XXVI). Optical resolution of (XXVI) by means of lipase PL-266 and vinyl acetate gives the chiral acetate (S)-(XXVII), which is rebenzylated with BnBr yielding the benzyl ether (XXVIII). The deacetylation of (XXVIII) with LiAlH4 in ethyl ether affords the carbinol (XXIX), which is oxidized with oxalyl chloride to the aldehyde (XXX). The condensation of (XXX) with the intermediate phosphonium salt (XXI) by means of n-BuLi in THF gives the olefin (XXXI), which is finally hydrogenated and debenzylated with H2 over Pd/C in ethyl acetate.

参考文献中间体

合成目标

【1】 Nozawa, M.; et al.; Enantioselective synthesis of (2R,4'R,8'R)-alpha-tocopherol (vitamin E) based on enzymatic function. Chem Pharm Bull 2000, 48, 2, 272.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXI)	40910	triphenyl[(3R,7R)-3,7,11-trimethyldodecyl]phosphonium bromide		C₃₃H₄₆BrP	详情	详情
(XXII)	21255	Trolox; Trolox C; 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylic acid	53188-07-1	C₁₄H₁₈O₄	详情	详情
(XXIII)	40911	methyl 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylate		C₁₅H₂₀O₄	详情	详情
(XXIV)	40912	methyl 6-(benzyloxy)-2,5,7,8-tetramethyl-2-chromanecarboxylate		C₂₂H₂₆O₄	详情	详情
(XXV)	18084	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(XXVI)	21256	2-(hydroxymethyl)-2,5,7,8-tetramethyl-6-chromanol		C₁₄H₂₀O₃	详情	详情
(XXVII)	40913	[(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl acetate		C₁₆H₂₂O₄	详情	详情
(XXVIII)	40914	[(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl acetate		C₂₃H₂₈O₄	详情	详情
(XXIX)	40915	[(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(XXX)	40916	(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carbaldehyde		C₂₁H₂₄O₃	详情	详情
(XXXI)	40917	(2S)-6-(benzyloxy)-2,5,7,8-tetramethyl-2-[(E,4R,8R)-4,8,12-trimethyl-1-tridecenyl]-3,4-dihydro-2H-chromene; benzyl (2S)-2,5,7,8-tetramethyl-2-[(E,4R,8R)-4,8,12-trimethyl-1-tridecenyl]-3,4-dihydro-2H-chromen-6-yl ether		C₃₆H₅₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reduction of carboxylic acid (Trolox) (I) with LiAlH4 in refluxing diethyl ether affords alcohol (TM) (II). Reaction of (II) in DMSO with maltose (III) and alpha-glucosidase in potassium phosphate buffer yields the final product.

参考文献中间体

合成目标

【1】 Murase, H.; et al.; Antioxidant activity of a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol. Free Radical Biol Med 1998, 24, 2, 217.
【2】 Murase, H.; et al.; Synthesis of a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, by alpha-glucosidase-catalyzed transglycosylation. Lipids 1997, 32, 1, 73.
【3】 Murase, H.; Tsujii, T.; Kunieda, T. (CCI Corporation); Chromanol glycoside and method for production thereof. US 5478812 .

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)	21255	Trolox; Trolox C; 6-hydroxy-2,5,7,8-tetramethyl-2-chromanecarboxylic acid	53188-07-1	C₁₄H₁₈O₄	详情	详情
(II)	21256	2-(hydroxymethyl)-2,5,7,8-tetramethyl-6-chromanol		C₁₄H₂₀O₃	详情	详情
(III)	41636	(2S,3R,4R,5S,6R)-6-(hydroxymethyl)-5-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-2,3,4-triol		C₁₂H₂₂O₁₁	详情	详情

Extended Information