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【结 构 式】

【分子编号】58004

【品名】(3R,4R)-4-(benzyloxy)-1,5-hexadien-3-ol

【CA登记号】

【 分 子 式 】C13H16O2

【 分 子 量 】204.26884

【元素组成】C 76.44% H 7.9% O 15.67%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

Diisopropylidene mannitol (I) was first converted into the dibutyltin derivative (II), which was subsequently mono-benzylated to (III). Acetylation of (III) with acetic anhydride in pyridine gave (IV). After acidic hydrolysis of the isopropylidene ketals of (IV), the resultant tetraol (V) was converted into tetramesylate (VI). Reductive elimination in (VI) with Zn and NaI produced diene (VII). The acetate group of (VII) was then hydrolyzed to (VIII) using NaOMe. Intermediate (VIII) was reacted with triethyl orthoacetate in the presence of propionic acid to generate the allyl vinyl ether (IX), which underwent a Claisen rearrangement to the diene-ester (X). Selective hydroboration-oxidation of the terminal double bond of (X) yielded the primary alcohol (XI). Subsequent benzyl group hydrogenolysis in (XI) furnished the target intermediate diol (XII).

1 Rao, A.V.R.; et al.; Synthesis of (3R,4R)-1,5-hexadien-3,4-diol and its unsymmetrical derivatives: Application to (R)-(+)-alpha-lipoic acid. Tetrahedron Lett 1987, 28, 19, 2183.
2 Yadav, J.S.; et al.; Synthesis of (3R,4R)-1,2-divinylglycol and its unsymmetrical derivatives: An application to the synthesis of R-(+)-alpha lipoic acid. J Carbohydr Chem 1990, 9, 2-3, 307.
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) 45944 (1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol 1707-77-3 C12H22O6 详情 详情
(II) 57998 (4R,5R)-2,2-dibutoxy-4,5-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,3,2-dioxastannolane C20H38O8Sn 详情 详情
(III) 57999 (1S,2S)-2-(benzyloxy)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1-ethanol C19H28O6 详情 详情
(IV) 58000 (1S,2R)-2-(benzyloxy)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl acetate C21H30O7 详情 详情
(V) 58001 (1R,2R,3R)-2-(benzyloxy)-1-[(1R)-1,2-dihydroxyethyl]-3,4-dihydroxybutyl acetate C15H22O7 详情 详情
(VI) 58002 (1S,2S,3R)-2-(benzyloxy)-1-{(1R)-1,2-bis[(methylsulfonyl)oxy]ethyl}-3,4-bis[(methylsulfonyl)oxy]butyl acetate C19H30O15S4 详情 详情
(VII) 58003 (1R,2R)-2-(benzyloxy)-1-vinyl-3-butenyl acetate C15H18O3 详情 详情
(VIII) 58004 (3R,4R)-4-(benzyloxy)-1,5-hexadien-3-ol C13H16O2 详情 详情
(IX) 58005 1-[({(1R,2R)-2-[(1-ethoxyvinyl)oxy]-1-vinyl-3-butenyl}oxy)methyl]benzene; benzyl (1R,2R)-2-[(1-ethoxyvinyl)oxy]-1-vinyl-3-butenyl ether C17H22O3 详情 详情
(X) 58006 ethyl (4E,6R)-6-(benzyloxy)-4,7-octadienoate C17H22O3 详情 详情
(XI) 58007 ethyl (E,6R)-6-(benzyloxy)-8-hydroxy-4-octenoate C17H24O4 详情 详情
(XII) 57958 ethyl (6S)-6,8-dihydroxyoctanoate C10H20O4 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VIII)

Esterification of diisopropylidene mannitol (I) with benzoyl chloride in pyridine afforded dibenzoate (II). Hydrolysis of the isopropylidene ketals of (II) with aqueous HOAc gave tetraol (III), which was further converted to tetramesylate (IV) on treatment with methanesulfonyl chloride and pyridine. Reductive elimination of the mesylate groups of (IV) using Zn dust and NaI yielded diene (V). The benzoate esters of (V) were then removed by treatment with sodium methoxide. The resultant divinylglycol (VI) was reacted with dibutyltin oxide to produce the tin derivative (VII), which was converted to the target intermediate, themono-benzyl ether (VIII), by treatment with benzyl bromide in hot DMF.

1 Rao, A.V.R.; et al.; Synthesis of (3R,4R)-1,5-hexadien-3,4-diol and its unsymmetrical derivatives: Application to (R)-(+)-alpha-lipoic acid. Tetrahedron Lett 1987, 28, 19, 2183.
2 Yadav, J.S.; et al.; Synthesis of (3R,4R)-1,2-divinylglycol and its unsymmetrical derivatives: An application to the synthesis of R-(+)-alpha lipoic acid. J Carbohydr Chem 1990, 9, 2-3, 307.
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) 45944 (1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol 1707-77-3 C12H22O6 详情 详情
(II) 58020 (1R,2R)-2-(benzoyloxy)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl benzoate C26H30O8 详情 详情
(III) 58021 (1R,2R,3R)-2-(benzoyloxy)-1-[(1R)-1,2-dihydroxyethyl]-3,4-dihydroxybutyl benzoate C20H22O8 详情 详情
(IV) 58022 (1S,2S,3R)-2-(benzoyloxy)-1-{(1R)-1,2-bis[(methylsulfonyl)oxy]ethyl}-3,4-bis[(methylsulfonyl)oxy]butyl benzoate C24H30O16S4 详情 详情
(V) 58023 (1R,2R)-2-(benzoyloxy)-1-vinyl-3-butenyl benzoate C20H18O4 详情 详情
(VI) 58024 (3R,4R)-1,5-hexadiene-3,4-diol C6H10O2 详情 详情
(VII) 58025 (4R,5R)-2,2-dibutoxy-4,5-divinyl-1,3,2-dioxastannolane C14H26O4Sn 详情 详情
(VIII) 58004 (3R,4R)-4-(benzyloxy)-1,5-hexadien-3-ol C13H16O2 详情 详情
Extended Information