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【结 构 式】 
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【分子编号】35011 【品名】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 【CA登记号】 |
【 分 子 式 】C23H26O9 【 分 子 量 】446.45404 【元素组成】C 61.88% H 5.87% O 32.25% |
合成路线1
该中间体在本合成路线中的序号：(LXI)The cyclization of 6-[1-hydroxy-1-(3,4,5-trimethoxyphenyl)methyl]-1,3-benzodioxol-5-carbaldehyde dimethylacetal (LVI) by means of AcOH gives 5-(3,4,5-trimethoxyphenyl)-1,3-dioxolo[4,5-f]isobenzofuran (LVII), which is submitted to a Diels-Alder cyclization with acetylenedicarboxylic acid dimethyl ester (LVIII) yielding the epoxy derivative (LIX). The selective reduction of (LIX) with LiBEt3H and H2 affords the carbinol (LX), which is treated with H2 over RaNi in order to open the epoxide ring to give 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 (LXII) with the suitable configuration. Finally, this compound is cyclized with DCC to the desired target compound.
| 【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 |
|---|---|---|---|---|---|---|
| (LVI) | 35007 | [6-(dimethoxymethyl)-1,3-benzodioxol-5-yl](3,4,5-trimethoxyphenyl)methanol | C20H24O8 | 详情 | 详情 | |
| (LVII) | 35008 | 4-furo[3,4-f][1,3]benzodioxol-5-yl-2,6-dimethoxyphenyl methyl ether; 5-(3,4,5-trimethoxyphenyl)furo[3,4-f][1,3]benzodioxole | C18H16O6 | 详情 | 详情 | |
| (LVIII) | 24551 | Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester | 762-42-5 | C6H6O4 | 详情 | 详情 |
| (LIX) | 35009 | dimethyl (1R,11S)-1-(3,4,5-trimethoxyphenyl)-5,7,14-trioxatetracyclo[9.2.1.0(2,10).0(4,8)]tetradeca-2(10),3,8,12-tetraene-12,13-dicarboxylate | C24H22O10 | 详情 | 详情 | |
| (LX) | 35010 | methyl (1R,11R,12S,13R)-13-(hydroxymethyl)-11-(3,4,5-trimethoxyphenyl)-5,7,14-trioxatetracyclo[9.2.1.0(2,10).0(4,8)]tetradeca-2(10),3,8-triene-12-carboxylate | C23H24O9 | 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 | |
| (LXII) | 35012 | (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-carboxylic acid | C22H24O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXI)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 |