(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 -Drug Synthesis Database

【结构式】

【分子编号】56087

【品名】(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

【CA登记号】

【分子式】C₁₇H₂₆O₆

【分子量】326.38984

【元素组成】C 62.56% H 8.03% O 29.41%

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：(III)

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

合成路线2

该中间体在本合成路线中的序号：(III)

Reduction of artemisinin (I) with DIBAL, followed by acetylation of the resultant lactol (II) with Ac2O/DMAP leads to dihydroartemisinin acetate (III). Treatment of the allylic dichloride (IV) with trimethylsilyllithium provides the bis-silane derivative (V). Then, coupling of dihydroartemisinin acetate (III) with bis-silane (V) in the presence of SnCl4 gives rise to the artemisinin dimer (VI).

参考文献中间体

合成目标

【1】 Posner, G.H.; Paik, I.-P.; Sur, S.; McRiner, A.J.; Borstnik, K.; Zie, S.; Shapiro, T.A.; Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy. J Med Chem 2003, 46, 6, 1060.

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)	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)	64026	3-chloro-2-(chloromethyl)-1-propene		C₄H₆Cl₂	详情	详情
(V)	64027	trimethyl{2-[(trimethylsilyl)methyl]-2-propenyl}silane		C₁₀H₂₄Si₂	详情	详情
(VI)	64028	(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-(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]methyl}-2-propenyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane		C₃₄H₅₂O₈	详情	详情

Extended Information