(3R,4R)-4-(benzyloxy)-1,5-hexadien-3-ol -Drug Synthesis Database

【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 合成路线2

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).

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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