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【结 构 式】

【分子编号】61744

【品名】(3aS,6R,7aS)-3,6-dimethyl-7-(3-oxobutyl)hexahydro-1-benzofuran-2(3H)-one

【CA登记号】

【 分 子 式 】C14H22O3

【 分 子 量 】238.32688

【元素组成】C 70.56% H 9.3% O 20.14%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The (+)-isolimonene (I) was submitted to a regioselective hydroboration with dicyclohexylborane to give the alcohol (II), which was oxidized with CrO3 to the corresponding carboxylic acid (III). The iodolactonization of (III) by means of KI, I2 and NaHCO3 yielded a separable, diastereomeric mixture of iodolactones (IV) + (V). The suitable isomer (IV) was condensed with methyl vinyl ketone (VI) by means of tris(trimethylsilyl)silane and AIBN in refluxing toluene to afford the alkylated lactone (VII) as an inseparable diastereomeric mixture. The ketonic group of (VII) was treated with ethanedithiol (VIII) and BF3/Et2O in dichloromethane to provide a separable mixture of thioketal lactones (IX)+(X). The suitable isomer (X) was hydrolyzed with NaOH in refluxing methanol to give the hydroxyacid (XI), which was treated with diazomethane to yield the corresponding methyl ester (XII). The oxidation of the OH group of (XII) by means of PCC affords the ketoester (XIII), which is submitted to a Wittig condensation with methoxymethyltriphenylphosphonium chloride (XIV) by means of KHMDS in THF/HMPA to provide the methoxymethylene derivative (XV). The cleavage of the dithioketal group of (XV) by means of HgCl2 and CaCO3 in acetonitrile regenerates the keto group giving compound (XVI), which is finally transformed into the target (+)-artemisinin by photooxidation with O2 in methanol in the presence of Rose Bengal, followed by a treatment with 70 % HClO4.

1 Yadav, J.S.; et al.; Stereoselective total synthesis of (+)-artemisinin. Tetrahedron Lett 2003, 44, 2, 387.
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) 61739 (1R)-(+)-trans-Isolimonene; (+)-p-Mentha-2,8-diene; (1R)-(+)-trans-Isolimonene with G.C. 5113-87-1 C10H16 详情 详情
(II) 61740 (2S)-2-[(1R,4R)-4-methyl-2-cyclohexen-1-yl]-1-propanol C10H18O 详情 详情
(III) 61741 (2S)-2-[(1R,4R)-4-methyl-2-cyclohexen-1-yl]propanoic acid C10H16O2 详情 详情
(IV) 61742 (3aS,6R,7R,7aR)-7-iodo-3,6-dimethylhexahydro-1-benzofuran-2(3H)-one C10H15IO2 详情 详情
(V) 61743 (3S,3aS,6R,7R,7aR)-7-iodo-3,6-dimethylhexahydro-1-benzofuran-2(3H)-one C10H15IO2 详情 详情
(VI) 30324 3-buten-2-one; methyl vinyl ketone 78-94-4 C4H6O 详情 详情
(VII) 61744 (3aS,6R,7aS)-3,6-dimethyl-7-(3-oxobutyl)hexahydro-1-benzofuran-2(3H)-one C14H22O3 详情 详情
(VIII) 27313 1,2-ethanedithiol 540-63-6 C2H6S2 详情 详情
(IX) 61745 (3aS,6R,7R,7aS)-3,6-dimethyl-7-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]hexahydro-1-benzofuran-2(3H)-one C16H26O2S2 详情 详情
(X) 61746 (3aS,6R,7S,7aS)-3,6-dimethyl-7-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]hexahydro-1-benzofuran-2(3H)-one C16H26O2S2 详情 详情
(XI) 61747 2-{(1S,2S,3S,4R)-2-hydroxy-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]cyclohexyl}propanoic acid C16H28O3S2 详情 详情
(XII) 61748 methyl 2-{(1S,2S,3S,4R)-2-hydroxy-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]cyclohexyl}propanoate C17H30O3S2 详情 详情
(XIII) 61749 methyl 2-{(1S,3S,4R)-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]-2-oxocyclohexyl}propanoate C17H28O3S2 详情 详情
(XIV) 39163 (methoxymethyl)(triphenyl)phosphonium chloride 4009-98-7 C20H20ClOP 详情 详情
(XV) 61750 methyl 2-{(1S,3S,4R)-2-[(E)-methoxymethylidene]-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]cyclohexyl}propanoate C19H32O3S2 详情 详情
(XVI) 10239 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C17H28O4 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VI)

 

1 Yadav JS, Satheesh BR, Sabitha G. 2003. Stereoselective total synthesis of (+) -artemisinin. Tetrahedron Lett, 44(2): 387~389.
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) 61739 (1R)-(+)-trans-Isolimonene; (+)-p-Mentha-2,8-diene; (1R)-(+)-trans-Isolimonene with G.C. 5113-87-1 C10H16 详情 详情
(II) 61740 (2S)-2-[(1R,4R)-4-methyl-2-cyclohexen-1-yl]-1-propanol C10H18O 详情 详情
(III) 61741 (2S)-2-[(1R,4R)-4-methyl-2-cyclohexen-1-yl]propanoic acid C10H16O2 详情 详情
(IV) 61742 (3aS,6R,7R,7aR)-7-iodo-3,6-dimethylhexahydro-1-benzofuran-2(3H)-one C10H15IO2 详情 详情
(V) 30324 3-buten-2-one; methyl vinyl ketone 78-94-4 C4H6O 详情 详情
(VI) 61744 (3aS,6R,7aS)-3,6-dimethyl-7-(3-oxobutyl)hexahydro-1-benzofuran-2(3H)-one C14H22O3 详情 详情
(VII) 61746 (3aS,6R,7S,7aS)-3,6-dimethyl-7-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]hexahydro-1-benzofuran-2(3H)-one C16H26O2S2 详情 详情
(VIII) 61748 methyl 2-{(1S,2S,3S,4R)-2-hydroxy-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]cyclohexyl}propanoate C17H30O3S2 详情 详情
(IX) 61749 methyl 2-{(1S,3S,4R)-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]-2-oxocyclohexyl}propanoate C17H28O3S2 详情 详情
(X) 61750 methyl 2-{(1S,3S,4R)-2-[(E)-methoxymethylidene]-4-methyl-3-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]cyclohexyl}propanoate C19H32O3S2 详情 详情
(XI) 10239 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C17H28O4 详情 详情
(XIII) 61743 (3S,3aS,6R,7R,7aR)-7-iodo-3,6-dimethylhexahydro-1-benzofuran-2(3H)-one C10H15IO2 详情 详情
(XIV) 61745 (3aS,6R,7R,7aS)-3,6-dimethyl-7-[2-(2-methyl-1,3-dithiolan-2-yl)ethyl]hexahydro-1-benzofuran-2(3H)-one C16H26O2S2 详情 详情
Extended Information