Dimoxaprost, HR-260, Hoe-260, -Drug Synthesis Database

【结构式】

【药物名称】Dimoxaprost, HR-260, Hoe-260

【化学名称】7-[(1RS,2RS,3RS)-2-[5-Ethoxy-3(R)-hydroxy-4,4-dimethyl-1(E)-pentenyl]-3-hydroxy-5-oxocyclopentyl]-5(Z)-heptenoic acid

【CA登记号】90243-98-4

【分子式】C₂₁H₃₄O₆

【分子量】382.50153

【开发单位】Aventis Pharma (Originator)

【药理作用】Antiulcer Drugs, GASTROINTESTINAL DRUGS, Prostaglandins

合成路线1 合成路线2 合成路线3

合成路线1

Synthesis of intermediate (VIII). The hydrochloration of 5-oxotricyclo[2.2.1.0~2,6~]heptane-3-carboxylic acid (II) gives 2-chloro-5-oxobicyclo[2.2.1]heptane-7-carboxylic acid (III), which is treated with peracetic acid yielding lactone (IV). This compound is treated with SOCl2 to obtain acyl chloride (V), which is converted into aldehyde (VI) by means H2 over Pd. The Horner-Emmons-Wiittig reaction of aldehyde (VI) and phosphonate (VII) by means NaH affords intermediate (VIII).

参考文献中间体

【1】 Peel, R.; Sutherland, J.K.; Beeley, N.R.A.; Tetrahedron 1981, 37, 411.
【2】 Jahne, G.; Wess, G.; Bartmann, W.; Beck, G.; Lerch, U.; Liebigs Ann Chem 1987, 321-326.
【3】 Beck, G.; Dimoxaprost. Drugs Fut 1987, 12, 12, 1101.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	28182	5-oxotricyclo[2.2.1.0(2,6)]heptane-3-carboxylic acid	70748-53-7	C₈H₈O₃	详情	详情
(III)	28183	2-chloro-5-oxobicyclo[2.2.1]heptane-7-carboxylic acid	52730-42-4	C₈H₉ClO₃	详情	详情
(IV)	28184	6-chloro-3-oxo-2-oxabicyclo[3.2.1]octane-8-carboxylic acid		C₈H₉ClO₄	详情	详情
(V)	28185	6-chloro-3-oxo-2-oxabicyclo[3.2.1]octane-8-carbonyl chloride		C₈H₈Cl₂O₃	详情	详情
(VI)	28186	6-chloro-3-oxo-2-oxabicyclo[3.2.1]octane-8-carbaldehyde		C₈H₉ClO₃	详情	详情
(VII)	28187	dimethyl 4-ethoxy-3,3-dimethyl-2-oxobutylphosphonate		C₁₀H₂₁O₅P	详情	详情
(VIII)	28188	6-chloro-8-[(E)-5-ethoxy-4,4-dimethyl-3-oxo-1-pentenyl]-2-oxabicyclo[3.2.1]octan-3-one		C₁₆H₂₃ClO₄	详情	详情

合成路线2

Synthesis of intermediate (XII). Ring cleavage and rearrangement of compound (VIII) affords enone (IXa) with an unprotected hydroxyl group. By stereoselective reduction of (IXa), diol (XIa) is obtained, which is finally protected by DHP to obtain intermediate (XII).

参考文献中间体

【1】 Jahne, G.; Wess, G.; Bartmann, W.; Beck, G.; Lerch, U.; Liebigs Ann Chem 1987, 321-326.
【2】 Peel, R.; Sutherland, J.K.; Beeley, N.R.A.; Tetrahedron 1981, 37, 411.
【3】 Beck, G.; Dimoxaprost. Drugs Fut 1987, 12, 12, 1101.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13684	3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran	110-87-2	C₅H₈O	详情	详情
(IXa)	28189	(3aR,4R,5R,6aS)-4-[(E)-5-ethoxy-4,4-dimethyl-3-oxo-1-pentenyl]-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one		C₁₆H₂₄O₅	详情	详情
(IXb)	28190	(3aR,4R,5R,6aS)-4-[(E)-5-ethoxy-4,4-dimethyl-3-oxo-1-pentenyl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate		C₂₉H₃₂O₆	详情	详情
(XIa)	28192	(3aR,4R,5R,6aS)-4-[(E,3R)-5-ethoxy-3-hydroxy-4,4-dimethyl-1-pentenyl]-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one		C₁₆H₂₆O₅	详情	详情
(XIb)	28193	(3aR,4R,5R,6aS)-4-[(E,3R)-5-ethoxy-3-hydroxy-4,4-dimethyl-1-pentenyl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate		C₂₉H₃₄O₆	详情	详情
(VIII)	28188	6-chloro-8-[(E)-5-ethoxy-4,4-dimethyl-3-oxo-1-pentenyl]-2-oxabicyclo[3.2.1]octan-3-one		C₁₆H₂₃ClO₄	详情	详情
(X)	28191	2,6-Di-tert-butyl-4-methylphenol diisobutylaluminum salt		C₂₃H₄₁AlO	详情	详情
(XII)	28194	(3aR,4R,5R,6aS)-4-[(E,3R)-5-ethoxy-4,4-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1-pentenyl]-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one		C₂₆H₄₂O₇	详情	详情

合成路线3

Intermediate (XII) is converted in four steps through the «Corey synthesis» to Dimoxaprost.

参考文献中间体

【1】 Peel, R.; Sutherland, J.K.; Beeley, N.R.A.; Tetrahedron 1981, 37, 411.
【2】 Jahne, G.; Wess, G.; Bartmann, W.; Beck, G.; Lerch, U.; Liebigs Ann Chem 1987, 321-326.
【3】 Beck, G.; Dimoxaprost. Drugs Fut 1987, 12, 12, 1101.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	28194	(3aR,4R,5R,6aS)-4-[(E,3R)-5-ethoxy-4,4-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1-pentenyl]-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one		C₂₆H₄₂O₇	详情	详情
(XIII)	28195	(3aR,4R,5R,6aS)-4-[(E,3R)-5-ethoxy-4,4-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1-pentenyl]-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-ol		C₂₆H₄₄O₇	详情	详情
(XIV)	13616	(4-Carboxybutyl)triphenylphosphonium bromide	17814-85-6	C₂₃H₂₄BrO₂P	详情	详情
(XV)	28196	(Z)-7-[(1R,2R,3R,5S)-2-[(E,3R)-5-ethoxy-4,4-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1-pentenyl]-5-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoic acid		C₃₁H₅₂O₈	详情	详情
(XVI)	28197	(Z)-7-[(1R,2R,3R)-2-[(E,3R)-5-ethoxy-4,4-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)-1-pentenyl]-5-oxo-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoic acid		C₃₁H₅₀O₈	详情	详情

Extended Information