methyl (E)-6-hydroperoxy-6-methoxy-2-undecenoate -Drug Synthesis Database

【结构式】

【分子编号】59685

【品名】methyl (E)-6-hydroperoxy-6-methoxy-2-undecenoate

【CA登记号】

【分子式】C₁₃H₂₄O₅

【分子量】260.33056

【元素组成】C 59.98% H 9.29% O 30.73%

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)

Treatment of gamma-butyrolactone (I) with N,O-dimethylhydroxylamine in the presence of dimethylaluminium chloride afforded the corresponding Weinreb amide (II), which was converted to the keto-alcohol (III) by addition of pentylmagnesium bromide. Swern oxidation of alcohol (III), followed by Wittig reaction of the resultant aldehyde (IV) with (methoxycarbonylmethylene)triphenylphosphorane (V), provided the unsaturated keto ester (VI). Subsequent scandium triflate-mediated peroxyhemiacetalyzation of ketone (VI) gave rise to (VII). Then, intramolecular Michael addition of the hydroperoxy ester (VII) in the presence of diethylamine generated the target cyclic peroxide.

参考文献中间体

合成目标

【1】 Murakami, N.; Horii, T.; Itagaki, S.; Kobayashi, M.; Kawanishi, M.; New readily accessible peroxides with high anti-malarial potency. Bioorg Med Chem Lett 2002, 12, 1, 69.

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)	20576	dihydro-2(3H)-furanone	96-48-0	C₄H₆O₂	详情	详情
(II)	59681	4-hydroxy-N-methoxy-N-methylbutanamide		C₆H₁₃NO₃	详情	详情
(III)	59682	1-hydroxy-4-nonanone		C₉H₁₈O₂	详情	详情
(IV)	59683	4-oxononanal		C₉H₁₆O₂	详情	详情
(V)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(VI)	59684	methyl (E)-6-oxo-2-undecenoate		C₁₂H₂₀O₃	详情	详情
(VII)	59685	methyl (E)-6-hydroperoxy-6-methoxy-2-undecenoate		C₁₃H₂₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Dimethylaluminium chloride-catalyzed ring opening of butyrolactone (I) with N,O-dimethylhydroxylamine furnishes the N-methoxy amide (II). Subsequent condensation of the Weinreb amide (II) with pentylmagnesium bromide (III) gives rise to the hydroxy ketone (IV). Further oxidation of the primary alcohol function of (IV) under Swern conditions leads to keto aldehyde (V). Then, Wittig condensation of aldehyde (V) with (methoxycarbonylmethylene) triphenylphosphorane (VI) affords the unsaturated ester (VII). Treatment of (VII) with urea-hydrogen peroxide in the presence of scandium triflate generates the hydroperoxide compound (VIII), which undergoes further intramolecular ring closure in the presence of triethylamine, leading to the 1,2-dioxane (IX). Enzymatic hydrolysis of ester (IX) employing pig liver esterase gives acid (X). After activation of (X) as the corresponding pentafluorophenyl ester (XI), condensation with propylamine in pyridine provides the title N-propyl amide

参考文献中间体

合成目标

【1】 Murakami, N.; Kawanishi, M.; Mostaqul, H.M.; Tsuruta, K.; Itagaki, S.; Horii, T.; Kobayashi, M.; Exploitation for new antimalarials using spongean peroxides as scaffolds. 22nd Symp Med Chem (Nov 27 2002, Shizuoka) 2002, Abst 1P-12.

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)	20576	dihydro-2(3H)-furanone	96-48-0	C₄H₆O₂	详情	详情
(II)	59681	4-hydroxy-N-methoxy-N-methylbutanamide		C₆H₁₃NO₃	详情	详情
(III)	31871	bromo(pentyl)magnesium	693-25-4	C₅H₁₁BrMg	详情	详情
(IV)	59682	1-hydroxy-4-nonanone		C₉H₁₈O₂	详情	详情
(V)	59683	4-oxononanal		C₉H₁₆O₂	详情	详情
(VI)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(VII)	59684	methyl (E)-6-oxo-2-undecenoate		C₁₂H₂₀O₃	详情	详情
(VIII)	59685	methyl (E)-6-hydroperoxy-6-methoxy-2-undecenoate		C₁₃H₂₄O₅	详情	详情
(IX)	60083	methyl 2-(6-methoxy-6-pentyl-1,2-dioxan-3-yl)acetate		C₁₃H₂₄O₅	详情	详情
(X)	60084	2-(6-methoxy-6-pentyl-1,2-dioxan-3-yl)acetic acid		C₁₂H₂₂O₅	详情	详情
(XI)	60085	2,3,4,5,6-pentafluorophenyl 2-(6-methoxy-6-pentyl-1,2-dioxan-3-yl)acetate		C₁₈H₂₁F₅O₅	详情	详情

Extended Information