trimethylsilyl 1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl ether; trimethyl[[1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl]oxy]silane -Drug Synthesis Database

【结构式】

【分子编号】42274

【品名】trimethylsilyl 1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl ether; trimethyl[[1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl]oxy]silane

【CA登记号】

【分子式】C₁₆H₂₆O₂Si₂

【分子量】306.55224

【元素组成】C 62.69% H 8.55% O 10.44% Si 18.32%

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：(IV)

Reduction of artemisinin (I) by means of NaBH4 in THF/MeOH followed by treatment with BH3·H2O in MeOH yields (II). Finally, beta-artemether (II) is condensed with TMS-enol ether (IV) [obtained by protection of diacetylbenzene (III) by means of TMSOTf and Et3N in THF] in the presence of TiCl4 in CH2Cl2.

参考文献中间体

合成目标

【1】 Posner, G.H.; Parker, M.H.; Ploypradith, P.; et al.; Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. J Med Chem 1999, 42, 21, 4275.
【2】 Parker, M.H.; Shapiro, T.A.; Ploypradith, P.; Posner, G.H.; Northrup, J.; Daughenbaugh, R.J.; Woo, S.H.; Murray, C.; Elias, J.S.; Zheng, Q.Y. (Hauser, Inc.; Johns Hopkins University); C-10 carbon-substd. artemisinin-like trioxane cpds. having antimalarial, antiproliferative and antitumour activities. EP 1043988; WO 9933461 .

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)	22369	Qinghaosu; Artemisine; (1R,4S,5R,8S,9R,12S,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-one	63968-64-9	C₁₅H₂₂O₅	详情	详情
(II)	31983	(1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecane; methyl (1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadec-10-yl ether	71963-77-4	C₁₆H₂₆O₅	详情	详情
(III)	42273	1-(4-acetylphenyl)-1-ethanone	1009-61-6	C₁₀H₁₀O₂	详情	详情
(IV)	42274	trimethylsilyl 1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl ether; trimethyl[[1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl]oxy]silane		C₁₆H₂₆O₂Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Reduction of artemisinin (I) with NaBH4 at low temperature provided dihydroartemisinin (II), which was subsequently converted to the alpha-acetate (III) upon treatment with acetyl chloride in pyridine. The bis(trimethylsilyl) enol ether (V) - prepared by silylation of 1,4-diacetylbenzene (IV) with trimethylsilyl triflate - was then coupled to dihydroartemisinin acetate (III) in the presence of SnCl4 at -78 C to produce a diastereoisomeric mixture of adducts (VIa-c). The title alpha,alpha-dimer was then isolated as a minor component by means of preparative HPLC.

参考文献中间体

合成目标

【1】 Borstnik, K.; Posner, G.H.; Paik, I.-H.; Dolan, P.; Kensler, T.W.; Xie, S.; Shapiro, T.A.; Northrop, J.; New chemical and biological aspects of artemisinin-derived trioxane dimers. Bioorg Med Chem 2002, 10, 1, 227.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIa)	56088	2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]-1-(4-{2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]acetyl}phenyl)-1-ethanone		C₄₀H₅₄O₁₀	详情	详情
(VIb)	56089	2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]-1-(4-{2-[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]acetyl}phenyl)-1-ethanone		C₄₀H₅₄O₁₀	详情	详情
(VIc)	56090	2-[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]-1-(4-{2-[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]acetyl}phenyl)-1-ethanone		C₄₀H₅₄O₁₀	详情	详情
(I)	22369	Qinghaosu; Artemisine; (1R,4S,5R,8S,9R,12S,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-one	63968-64-9	C₁₅H₂₂O₅	详情	详情
(II)	22370	Dihydroartemisinin; (1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-ol		C₁₅H₂₄O₅	详情	详情
(III)	56087	(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl acetate		C₁₇H₂₆O₆	详情	详情
(IV)	42273	1-(4-acetylphenyl)-1-ethanone	1009-61-6	C₁₀H₁₀O₂	详情	详情
(V)	42274	trimethylsilyl 1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl ether; trimethyl[[1-(4-[1-[(trimethylsilyl)oxy]vinyl]phenyl)vinyl]oxy]silane		C₁₆H₂₆O₂Si₂	详情	详情

Extended Information