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【结 构 式】 
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【分子编号】34956 【品名】5-(3,4,5-trimethoxyphenyl)-7H-[1,3]dioxolo[4,5-g]isochromen-7-one 【CA登记号】 |
【 分 子 式 】C19H16O7 【 分 子 量 】356.33184 【元素组成】C 64.04% H 4.53% O 31.43% |
合成路线1
该中间体在本合成路线中的序号：(I)The Diels-Alder cyclization of 5-(3,4,5-trimethoxyphenyl)-7H-pyrano[3,4-f][1,3]benzodioxol-7-one (I) with the chiral dihydrofuranone (II) in hot acetonitrile gives the pentacyclic anhydride (III), which is opened with warm acetic acid yielding the carboxylic acid (IV). Hydrogenation of the benzylic double bond of (IV) with H2 over Pd/C affords (V), which is treated with lead tetraacetate and acetic acid in THF to give the acetoxy compound (VI). The hydrolysis of the acetoxy group and the menthol hemiacetal group with HCl in hot dioxane yields the diol (VII), which is treated with diazomethane in ether/methanol affording the aldehyde (VIII). The reduction of the aldehyde group of (VIII) with LiEt3BH in THF gives the diol (IX) as a diastereomeric mixture, which is treated with HCl in THF to afford the diol (X) with the right conformation. Finally, this compound is lactonized to the target compound with ZnCl2 in THF.
| 【1】 Jones, D.W.; Bush, E.J.; Asymmetric total synthesis of (-)-podophyllotoxin. J Chem Soc Chem Commun 1993, 1200. |
| 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) | 34956 | 5-(3,4,5-trimethoxyphenyl)-7H-[1,3]dioxolo[4,5-g]isochromen-7-one | C19H16O7 | 详情 | 详情 | |
| (II) | 34957 | (5R)-5-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]-2(5H)-furanone | C14H22O3 | 详情 | 详情 | |
| (III) | 34958 | (1R,11R,12R,13R,16R)-13-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]-1-(3,4,5-trimethoxyphenyl)-5,7,14,17-tetraoxapentacyclo[9.5.2.0(2,10).0(4,8).0(12,16)]octadeca-2(10),3,8-triene-15,18-dione | C33H38O10 | 详情 | 详情 | |
| (IV) | 34959 | (5R,5aR,6R)-6-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxole-5-carboxylic acid | C33H38O10 | 详情 | 详情 | |
| (V) | 34960 | (5R,5aR,6R,8aR,9R)-6-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxole-5-carboxylic acid | C33H40O10 | 详情 | 详情 | |
| (VI) | 34961 | (5R,5aS,6R,8aR,9R)-6-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl acetate | C34H42O10 | 详情 | 详情 | |
| (VII) | 34962 | (5R,5aR,8R,8aS)-8,9-dihydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C22H22O9 | 详情 | 详情 | |
| (VIII) | 34963 | methyl (5R,6R,7S)-7-formyl-8-hydroxy-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate | C23H24O9 | 详情 | 详情 | |
| (IX) | 34964 | methyl (5R,6R,7R)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate | C23H26O9 | 详情 | 详情 | |
| (X) | 34965 | methyl (5R,6R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate | C23H26O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The Diels-Alder cyclization of 5-(3,4,5-trimethoxyphenyl)-7H-pyrano[3,4-f][1,3]benzodioxol-7-one (I) with dimethyl maleate (LXIII) gives the expected adduct (LXIV), which by thermal extrusion of CO2 yields the dihydronaphthodioxole (LXV). This compound is then converted to dihydroxycompound (X), which is finally cyclized by means of ZnCl2 to provide the target compound. The Diels-Alder cyclization of 5-(3,4,5-trimethoxyphenyl)-7H-pyrano[3,4-f][1,3]benzodioxol-7-one (I) with dimethyl fumarate (LXVI) gives the expected adduct (LXVII), which by hydrogenation with H2 over Pd/C yields the tricarboxylic acid derivative (LXVIII). The reaction of (LXVIII) with Pb(OAc)4 affords the acetoxy derivative (LXIX), which is selectively reduced with LiBEt3H providing the diol (LXI) with the wrong configuration at the secondary OH group. The treatment of (LXI) with aqueous acid isomerizes the secondary OH group to give the previously described (X) with the suitable configuration.
| 【1】 Ward, R.S.; Synthesis of podophyllotoxin and related compounds. Synthesis 1992, 719. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXVLIII) | 35016 | (5R,6R,7R,8R)-6,7-bis(methoxycarbonyl)-8-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-5-carboxylic acid | C25H26O11 | 详情 | 详情 | |
| (I) | 34956 | 5-(3,4,5-trimethoxyphenyl)-7H-[1,3]dioxolo[4,5-g]isochromen-7-one | C19H16O7 | 详情 | 详情 | |
| (X) | 34965 | methyl (5R,6R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate | C23H26O9 | 详情 | 详情 | |
| (LXI) | 35011 | methyl (5R,6R,7R,8S)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate | C23H26O9 | 详情 | 详情 | |
| (LXIII) | 17206 | dimethyl (Z)-2-butenedioate; Dimethyl Maleate | 23055-10-9 | C6H8O4 | 详情 | 详情 |
| (LXIV) | 35013 | dimethyl (1S,11S,14R,15S)-13-oxo-11-(3,4,5-trimethoxyphenyl)-5,7,12-trioxatetracyclo[9.2.2.0(2,10).0(4,8)]pentadeca-2(10),3,8-triene-14,15-dicarboxylate | C25H24O11 | 详情 | 详情 | |
| (LXV) | 35014 | dimethyl (5R,6R)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6,7-dicarboxylate | C24H24O9 | 详情 | 详情 | |
| (LXVI) | 35018 | dimethyl (E)-2-butenedioate | 624-49-7 | C6H8O4 | 详情 | 详情 |
| (LXVII) | 35015 | dimethyl (1R,11R,14S,15S)-13-oxo-11-(3,4,5-trimethoxyphenyl)-5,7,12-trioxatetracyclo[9.2.2.0(2,10).0(4,8)]pentadeca-2(10),3,8-triene-14,15-dicarboxylate | C25H24O11 | 详情 | 详情 | |
| (LXIX) | 35017 | dimethyl (5S,6S,7R,8R)-5-(acetoxy)-8-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6,7-dicarboxylate | C26H28O11 | 详情 | 详情 |