6-oxabicyclo[3.1.0]hexane -Drug Synthesis Database

【结构式】

【分子编号】38011

【品名】6-oxabicyclo[3.1.0]hexane

【CA登记号】285-67-6

【分子式】C₅H₈O

【分子量】84.11792

【元素组成】C 71.39% H 9.59% O 19.02%

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：(X)

The addition of HCl to cyclopentadiene (I) gives 3-chlorocyclopentene (II), which is converted to racemic 2-cyclopentene-1-carboxylic acid (III). Optical resolution of (II) by crystallization of its (-)-1-phenylethylamine yields the desired enantiomer (IV), which is reduced with LiAlH4 in ethyl ether affording the chiral carbinol (V) (ee 98%). The reaction of (V) successively with BuLi, CO2 and I2 provides the iodinated cyclic carbonate (VI), which is treated with DBU in hot toluene to give the unsaturated cyclic carbonate (VII). The condensation of (VII) with 2-amino-6-chloropurine (VIII) by means of a Pd catalyst yields the carbocyclic purine (IX), which is finally hydrolyzed with aqueous NaOH to afford the target carbocyclic guanine. Alternatively, carbinol (V) can also be obtained by the vitamin B12/Zn/NH4Cl-catalyzed isomerization of 1,2-epoxycyclopentane (X) to the chiral cyclopentenol (XI), which by a [2,3]-sigmatropic Wittig rearrangement with KH, ICH2-SnBu4 and BuLi yields the target carbinol (V). However, the enantiomeric excess obtained is only ee 54%.

参考文献中间体

合成目标

【1】 Hildbrand, S.; et al.; A short synthesis of (-)-carbovir. Helv Chim Acta 1994, 77, 5, 1236.

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)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(II)	19541	3-chloro-1-cyclopentene		C₅H₇Cl	详情	详情
(III)	45419	2-cyclopentene-1-carboxylic acid		C₆H₈O₂	详情	详情
(IV)	45420	(1S)-2-cyclopentene-1-carboxylic acid		C₆H₈O₂	详情	详情
(V)	45421	(1S)-2-cyclopenten-1-ylmethanol		C₆H₁₀O	详情	详情
(VI)	45422	(4aR,7S,7aS)-7-iodohexahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₉IO₃	详情	详情
(VII)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(VIII)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(IX)	45398	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl methyl carbonate		C₁₃H₁₄ClN₅O₃	详情	详情
(X)	38011	6-oxabicyclo[3.1.0]hexane	285-67-6	C₅H₈O	详情	详情
(XI)	45423	(1R)-2-cyclopenten-1-ol		C₅H₈O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

This compound has been obtained by two similar ways: 1) By condensation of the chloropurine (I) with (1S-trans)-2-aminocyclopentanol (1S-trans)-(II) by means of DEA in refluxing isopropanol. 2) The condensation of chloropurine (I) with (rac-trans)-2-aminocyclopentanol (rac-trans)-(II) (obtained by reaction of cyclopentene oxide (III) with ammonia) give a diastereomeric mixture, from which the target compound can be isolated by flash chromatography.

参考文献中间体

合成目标

【1】 Evans, B. (Glaxo Wellcome plc); Adenosine derivs.. AU 8827401; BE 1002167; CH 677495; DE 3843609; EP 0322242; FR 2663936; US 5032583 .
【2】 Knutsen, L.J.S.; Lau, J. (Novo Nordisk A/S); Purine derivs.. US 5672588 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(1S-trans)-(II)	38010	(1S,2S)-2-aminocyclopentanol		C₅H₁₁NO	详情	详情
(rac)-(II)	63649	2-aminocyclopentanol		C₅H₁₁NO	详情	详情
(I)	18716	6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol	2004-06-0	C₁₀H₁₁ClN₄O₄	详情	详情
(III)	38011	6-oxabicyclo[3.1.0]hexane	285-67-6	C₅H₈O	详情	详情

Extended Information