(5S)-2,2-dimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-one -Drug Synthesis Database

【结构式】

【分子编号】52835

【品名】(5S)-2,2-dimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-one

【CA登记号】

【分子式】C₁₀H₁₄O₃

【分子量】182.21936

【元素组成】C 65.92% H 7.74% O 26.34%

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 chiral cyclohexenone intermediate (VII) was prepared as follows. Epoxide ring opening of (S)-glycidol (I) with the Grignard reagent (II) produced diol (III), which was protected as the isopropylidene ketal (IV) by treatment with 2,2-dimethoxypropane. Addition of bromine to olefin (IV) and further cyclization of the resultant dibromide in the presence of potassium hexamethyldisilazide gave rise to the spiro cyclopentene (V). Ozonolysis of (V), followed by reductive work-up, yielded the keto aldehyde (VI), which upon treatment with KOH underwent intramolecular aldol condensation to the target cyclopentenone (VII).

参考文献中间体

合成目标

【1】 Taber, D.F.; et al.; Synthesis of (-)-fumagillin. J Am Chem Soc 1999, 121, 23, 5589.

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)	19241	(2S)oxiranylmethanol	60456-23-7	C₃H₆O₂	详情	详情
(II)	52830	2-Methylallylmagnesium chloride		C₄H₇ClMg	详情	详情
(III)	52831	(2R)-5-methyl-5-hexene-1,2-diol		C₇H₁₄O₂	详情	详情
(IV)	52832	(4R)-2,2-dimethyl-4-(3-methyl-3-butenyl)-1,3-dioxolane		C₁₀H₁₈O₂	详情	详情
(V)	52833	(5S)-2,2,7-trimethyl-1,3-dioxaspiro[4.4]non-6-ene		C₁₀H₁₆O₂	详情	详情
(VI)	52834	(4R)-2,2-dimethyl-4-(3-oxobutyl)-1,3-dioxolane-4-carbaldehyde		C₁₀H₁₆O₄	详情	详情
(VII)	52835	(5S)-2,2-dimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-one		C₁₀H₁₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Lithiation of dihydrofuran (VIII), followed by the addition of tributylstannyllithium, gave an intermediate (IX) that was quenched with methyl iodide to produce alcohol (X). Silylation of alcohol (X) with tert-butyl dimethylsilyl chloride then gave silyl ether (XI). Copper-catalyzed conjugate addition of the organolithium reagent derived from (XI) to the intermediate enone (VII), with subsequent enolate trapping with triethylsilyl chloride, afforded adduct (XII) as the major diastereoisomer. Epoxidation of the silyl enol ether (XII) with m-chloroperbenzoic acid, followed by selective desilylation using tetrabutylammonium fluoride/ammonium chloride, gave rise to hydroxy ketone (XIII). Methylation of (XIII) in the presence of silver oxide yielded methyl ether (XIV). Then, the keto group of (XIV) was stereoselectively reduced to (XV) employing L-selectride. After protection of the hydroxyl group of (XV) as the benzoate ester, simultaneous deprotection of the ketal and silyl ether functions under acidic conditions provided triol (XVI). Oxidative cleavage of the 1,2-diol moiety of (XVI) with NaIO4 gave ketone (XVII). This was converted to epoxide (XVIII) by stereoselective addition of in situ generated trimethylsulfoxonium ylide.

参考文献中间体

合成目标

【1】 Taber, D.F.; et al.; Synthesis of (-)-fumagillin. J Am Chem Soc 1999, 121, 23, 5589.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	52835	(5S)-2,2-dimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-one		C₁₀H₁₄O₃	详情	详情
(VIII)	22766	2,3-dihydrofuran	1191-99-7	C₄H₆O	详情	详情
(IX)	52836	[(E)-4-oxido-1-(tributylstannyl)-1-butenyl]lithium		C₁₆H₃₂LiOSn	详情	详情
(X)	52837	(E)-4-(tributylstannyl)-3-penten-1-ol		C₁₇H₃₆OSn	详情	详情
(XI)	52838	tert-butyl(dimethyl){[(E)-4-(tributylstannyl)-3-pentenyl]oxy}silane; tert-butyl(dimethyl)silyl (E)-4-(tributylstannyl)-3-pentenyl ether		C₂₃H₅₀OSiSn	详情	详情
(XII)	52839	tert-butyl(dimethyl)silyl (E)-4-{(5S,6R)-2,2-dimethyl-8-[(triethylsilyl)oxy]-1,3-dioxaspiro[4.5]dec-7-en-6-yl}-3-pentenyl ether; tert-butyl[((E)-4-{(5S,6R)-2,2-dimethyl-8-[(triethylsilyl)oxy]-1,3-dioxaspiro[4.5]dec-7-en-6-yl}-3-pentenyl)oxy]dimethylsilane		C₂₇H₅₂O₄Si₂	详情	详情
(XIII)	52840	(5S,6S,7S)-6-((E)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-1-butenyl)-7-hydroxy-2,2-dimethyl-1,3-dioxaspiro[4.5]decan-8-one		C₂₁H₃₈O₅Si	详情	详情
(XIV)	52841	(5S,6S,7S)-6-((E)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-1-butenyl)-7-methoxy-2,2-dimethyl-1,3-dioxaspiro[4.5]decan-8-one		C₂₂H₄₀O₅Si	详情	详情
(XV)	52842	(5S,6S,7S,8R)-6-((E)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-1-butenyl)-7-methoxy-2,2-dimethyl-1,3-dioxaspiro[4.5]decan-8-ol		C₂₂H₄₂O₅Si	详情	详情
(XVI)	52843	(1R,2S,3S,4S)-4-hydroxy-4-(hydroxymethyl)-3-[(E)-4-hydroxy-1-methyl-1-butenyl]-2-methoxycyclohexyl benzoate		C₂₀H₂₈O₆	详情	详情
(XVII)	52844	(1R,2S,3S)-3-[(E)-4-hydroxy-1-methyl-1-butenyl]-2-methoxy-4-oxocyclohexyl benzoate		C₁₉H₂₄O₅	详情	详情
(XVIII)	52845	(3R,4S,5S,6R)-4-[(E)-4-hydroxy-1-methyl-1-butenyl]-5-methoxy-1-oxaspiro[2.5]oct-6-yl benzoate		C₂₀H₂₆O₅	详情	详情

Extended Information