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【结 构 式】 
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【分子编号】41878 【品名】8-iodo-1-naphthyl methyl ether; 1-iodo-8-methoxynaphthalene 【CA登记号】 |
【 分 子 式 】C11H9IO 【 分 子 量 】284.09633 【元素组成】C 46.51% H 3.19% I 44.67% O 5.63% |
合成路线1
该中间体在本合成路线中的序号：(VI)The oxidation of 4,8-dimethoxynaphthalene-1,5-diol (I) with FeCl3 in CH3CN/MeOH gives the naphthoquinone (II), which is submitted to a Diels Alder condensation with cyclopentadiene (III) yielding the methanoanthraquinone (IV). The reduction of (IV) with NaBH4 in THF/methanol affords the triol (V), which is condensed with 1-iodo-8-methoxynaphthalene (VI) by means of Cu2O in refluxing pyridine providing the diaryl ether (VII). The demethylation of (VII) by means of lithium diphenylphosphine in THF gives the tetrahydroxy compound (VIII), which is cyclized by means of PhI(OAc)2 in hexafluoroisopropanol yielding the spiro-13-dioxane derivative (IX). The selective silylation of (IX) with TBDMS-OTf and lutidine in dichloromethane affords the silyl ether (X), which is oxidized with pyridinium dichromate (PDC) in DMF to provide the diketonic compound (XI). The epoxidation of (XI) with H2O2 and K2CO3 in THF/water gives the diepoxy compound (XII), which is submitted to a retro Diels Alder reaction in refluxing diphenyl ether yielding the silylated precursor (XIII). Finally this compound is desilylated with HF in acetonitrile/water.
| 【1】 Wipf, P.; Jung, J.-K.; Formal total synthesis of (+)-diepoxin sigma. J Org Chem 2000, 65, 20, 6319. |
| 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) | 41874 | 4,8-dimethoxy-1,5-naphthalenediol | C12H12O4 | 详情 | 详情 | |
| (II) | 41875 | 5-hydroxy-8-methoxynaphthoquinone | C11H8O4 | 详情 | 详情 | |
| (III) | 11183 | 1,3-Cyclopentadiene | C5H6 | 详情 | 详情 | |
| (IV) | 41876 | (1R,2R,11S,12S)-5-hydroxy-8-methoxytetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,10-dione | C16H14O4 | 详情 | 详情 | |
| (V) | 41877 | (1R,2R,3R,10S,11S,12S)-8-methoxytetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,5,10-triol | C16H18O4 | 详情 | 详情 | |
| (VI) | 41878 | 8-iodo-1-naphthyl methyl ether; 1-iodo-8-methoxynaphthalene | C11H9IO | 详情 | 详情 | |
| (VII) | 41879 | (1S,2S,3S,10R,11R,12R)-5-methoxy-8-[(8-methoxy-1-naphthyl)oxy]tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,10-diol | C27H26O5 | 详情 | 详情 | |
| (VIII) | 41880 | (1S,2S,3S,10R,11R,12R)-8-[(8-hydroxy-1-naphthyl)oxy]tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,5,10-triol | C25H22O5 | 详情 | 详情 | |
| (IX) | 41881 | C25H20O5 | 详情 | 详情 | ||
| (X) | 41882 | C31H34O5Si | 详情 | 详情 | ||
| (XI) | 41883 | C31H32O5Si | 详情 | 详情 | ||
| (XII) | 41884 | C31H32O7Si | 详情 | 详情 | ||
| (XIII) | 41885 | C26H26O7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Formation of ketal (III) is achieved by treatment of 5-hydroxy-8-methoxy-1-tetralone (I) with ethylene glycol (II) and pyridinium p-toluenesulfonate (PPTS) in benzene. Coupling of hydroxy derivative (III) with 8-iodo-1-methoxynaphthalene (IV) by means of Cu2O and K2CO3 in refluxing pyridine provides naphthyl ether (V), which is then hydrolyzed to ketone (VI) by means of TsOH in acetone/H2O. Demethylation of derivative (VI) is then performed by treatment with BBr3 in dichloromethane to yield hydroxy derivative (VII), which is reduced by means of LiAlH4 in Et2O to give triol (VIII). Oxidative cyclization of (VIII) using PhI(OAc)2 in trifluoroethanol affords naphthalene spiroketal (IX), which is converted into palmarumycin CP1 (X) by a two-step protocol consisting in a first oxidation with Dess-Martin periodane (and subsequent purification) followed by aromatization with MnO2 in dichloromethane. Finally, the target product is obtained by a Mitsunobu reaction of derivative (X) with alcohol (XI) using polystyrene-bound triphenylphosphine and DEAD in dichloromethane.
| 【1】 Wipf, P.; et al.; Synthesis and biological evaluation of deoxypreussomerin A and palmarumycin CP1 and related naphthoquinone spiroketals. Tetrahedron 2001, 57, 2, 283. |
| 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) | 46802 | 5-hydroxy-8-methoxy-3,4-dihydro-1(2H)-naphthalenone | C11H12O3 | 详情 | 详情 | |
| (II) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (III) | 46803 | C13H16O4 | 详情 | 详情 | ||
| (IV) | 41878 | 8-iodo-1-naphthyl methyl ether; 1-iodo-8-methoxynaphthalene | C11H9IO | 详情 | 详情 | |
| (V) | 46804 | C24H24O5 | 详情 | 详情 | ||
| (VI) | 46805 | 8-methoxy-5-[(8-methoxy-1-naphthyl)oxy]-3,4-dihydro-1(2H)-naphthalenone | C22H20O4 | 详情 | 详情 | |
| (VII) | 46806 | 8-hydroxy-5-[(8-hydroxy-1-naphthyl)oxy]-3,4-dihydro-1(2H)-naphthalenone | C20H16O4 | 详情 | 详情 | |
| (VIII) | 46807 | 5-[(8-hydroxy-1-naphthyl)oxy]-1,2,3,4-tetrahydro-1,8-naphthalenediol | C20H18O4 | 详情 | 详情 | |
| (IX) | 46808 | C20H16O4 | 详情 | 详情 | ||
| (X) | 46809 | C20H12O4 | 详情 | 详情 | ||
| (XI) | 13848 | 2-Furylmethanol; Furfuryl Alcohol | 98-00-0 | C5H6O2 | 详情 | 详情 |