4-cyclopentene-1,3-diol -Drug Synthesis Database

【结构式】

【分子编号】21533

【品名】4-cyclopentene-1,3-diol

【CA登记号】

【分子式】C₅H₈O₂

【分子量】100.11732

【元素组成】C 59.98% H 8.05% O 31.96%

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：(VII)

The reaction of 3(R)-(tert-butyldimethylsilyloxy)-4(R)-methoxy-4(R)-methyl-1-(tributylstannyl)-1(E)-octene (II) with butyllithium, cuprous iodide and tributylphosphine gives an intermediate copper derivative which is condensed first with 4(R)-(tert-butyldimethylsilyloxy)-2-cyclopentenone (I) and then with methyl 6-formylhexanoate (III) to give the 7-hydroxy PGE1 derivative (IV). The dehydration of (IV) with mesyl chloride yields the unsaturated PGE compound (V), which is reduced with tributystannyl hydride and finally deprotected with acetic acid in THF. The starting products (I) and (II) are obtained as follows: 1) The oxidation of cyclopentadiene (VI) gives 2-cyclopentene-1,4-diol (VII), which is acetylated to the diacetate (VIII). Selective hydrolysis of (VIII) yields (1S, 4R)-4-hydroxy-2-cyclopentenyl acetate (IX), which is protected with tert-butyldimethylsilyl chloride to the protected acetate (X). Partial hydrolysis of (X) affords the semiprotected alcohol (XI), which is finally oxidized to the cyclopentenone (I).

参考文献中间体

合成目标

【1】 Kolb, M.; Van Hijfte, L.; Ireland, R.E.; A highly convergent synthesis of mexiprostil: 16(R) 16-methoxy 16-methyl PGE1 methyl ester. Tetrahedron Lett 1988, 29, 51, 6769.

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)	13805	(4R)-4-[[tert-Butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-one		C₁₁H₂₀O₂Si	详情	详情
(II)	21528	(1R,2R,3E)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(tributylstannyl)-3-butenyl methyl ether		C₂₈H₆₀O₂SiSn	详情	详情
(III)	21529	methyl 7-oxoheptanoate	35376-00-2	C₈H₁₄O₃	详情	详情
(IV)	21530	methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentyl]-7-hydroxyheptanoate		C₃₅H₆₈O₇Si₂	详情	详情
(V)	21531	methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentylidene]heptanoate		C₃₅H₆₆O₆Si₂	详情	详情
(VI)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(VII)	21533	4-cyclopentene-1,3-diol		C₅H₈O₂	详情	详情
(VIII)	21534	4-(acetoxy)-2-cyclopenten-1-yl acetate		C₉H₁₂O₄	详情	详情
(IX)	21535	(1R,4R)-4-hydroxy-2-cyclopenten-1-yl acetate		C₇H₁₀O₃	详情	详情
(X)	21536	(1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-yl acetate		C₁₃H₂₄O₃Si	详情	详情
(XI)	21537	(1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-ol		C₁₁H₂₂O₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(cis/trans)(IV)

The reaction of cyclopentadiene (I) with Br2 gives 1,4-dibromo-2-cyclopentene (II), which is treated with potassium acetate in tert-butanol yielding 1,4-diacetoxy-2-cyclopentene (III). The hydrolysis of (III) with KHCO3 in methanol affords 2-cyclopentene-1,4-diol (IV) as a mixture of the cis and trans isomers. The treatment of (cis/trans) (IV) or (cis) (IV) with pancreatin, vinyl acetate (V) and triethylamine gives (1R,4S)-4-acetoxy-2-cyclopenten-1-ol (VI), which is hydrogenated with H2 over RaNi in ethanol to yield the corresponding saturated (1S,3R)-3-acetoxycyclopentanol (VII). The reaction of (VII) with methanesulfonyl chloride and TEA in dichloromethane affords the corresponding mesylate (VIII), which is condensed with adenine (IX) by means of NaH in hot DMF providing the final intermediate (X). Finally, this compound is deacetylated with HCl in refluxing ethanol.

参考文献中间体

合成目标

【1】 Borcherding, D.R.; et al.; Carbocyclic nucleosides as inhibitors of human Tumor Necrosis Factor-alpha production: Effects of the stereoisomers of (3-hydroxycyclopentyl)adenines. J Med Chem 1996, 39, 13, 2615.
【2】 Watson, T.J.N.; et al.; Development of the carbocyclic nucleoside MDL 201449A. A tumor necrosis factor-alpha inhibitor. Org Process Res Dev 1998, 2, 6, 357.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(cis/trans)(IV)	21533	4-cyclopentene-1,3-diol		C₅H₈O₂	详情	详情
(cis)(IV)	33168	(1R,3S)-4-cyclopentene-1,3-diol		C₅H₈O₂	详情	详情
(I)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(II)	33167	3,5-dibromo-1-cyclopentene		C₅H₆Br₂	详情	详情
(III)	21534	4-(acetoxy)-2-cyclopenten-1-yl acetate		C₉H₁₂O₄	详情	详情
(V)	24543	vinyl acetate	108-05-4	C₄H₆O₂	详情	详情
(VI)	33169	(1S,4R)-4-hydroxy-2-cyclopenten-1-yl acetate		C₇H₁₀O₃	详情	详情
(VII)	33170	(1R,3S)-3-hydroxycyclopentyl acetate		C₇H₁₂O₃	详情	详情
(VIII)	33171	(1R,3S)-3-[(methylsulfonyl)oxy]cyclopentyl acetate		C₈H₁₄O₅S	详情	详情
(IX)	10343	9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine	73-24-5	C₅H₅N₅	详情	详情
(X)	33172	(1R,3R)-3-(6-amino-9H-purin-9-yl)cyclopentyl acetate		C₁₂H₁₅N₅O₂	详情	详情

Extended Information