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【结 构 式】 
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【分子编号】48745 【品名】 【CA登记号】 |
【 分 子 式 】C21H23NO5 【 分 子 量 】369.41736 【元素组成】C 68.28% H 6.28% N 3.79% O 21.65% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The asymmetric reduction of the carbonyl group of tetracyclic compound (I) by means of BH3 and a chiral borane catalyst in THF gives the (R)-alcohol (II), which by a Sharpless epoxidation yields the chiral epoxide (III). The reaction of the (cis)-(III) with (-)-camphanic acid (IV), DAD and PPh3 under Mitsunobu conditions affords after chromatographic purification the (trans)-camphanate (V), which is submitted to a rearrangement reaction by means of BF3/Et2O in dichloromethane to provide the tetracyclic spiro compound (VI). The protection of the ketonic group of (VI) by means of silylated ethyleneglycol and Tms-OTf gives the cyclic ketal (VII), which is treated with NaOH in methanol and the resulting alcohol oxidized with DMP in dichloromethane to yield the monoprotected diketone (VIII). The disulfenylation of (VIII) affords the disulfide (IX), which by treatment with TFA and oxidation with MCPBA provides the unsaturated sulfinyl (X). The cyclization of (X) with the homophthalic anhydride (XI) (obtained from trimethoxybromobenzene (XII)), followed by methylation of the resulting free OH group with MeI and K2CO3 in DMF furnishes the spiro-hexacyclic compound (XIII). The selective demethylation of (XIII) with Tms-I in dichloromethane gives the pyridinone derivative (XIV), which is oxidized at the methyl group with SeO2 to yield the carbaldehyde (XV). The condensation of (XV) with the phosphonium bromide (XVI) by means of BuLi in THF affords the precursor (XVII), which is finally demethylated with BBr3 and submitted to oxidation by air to provide the target compound.
| 【1】 Kitagaki, S.; Kita, Y.; Fujioka, H.; Iio, K.; Yoshida, Y.; Higuchi, K.; Akai, S.; Asymmetric total synthesis of fredericamycin A. Angew Chem. Int Ed Engl 1999, 38, 5, 683. |
| 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) | 48738 | 10,11-dimethoxy-8-methyl-2,3,4,5-tetrahydro-1H-indeno[5,4-g]isoquinolin-1-one | C19H19NO3 | 详情 | 详情 | |
| (II) | 48739 | (1R)-10,11-dimethoxy-8-methyl-2,3,4,5-tetrahydro-1H-indeno[5,4-g]isoquinolin-1-ol | C19H21NO3 | 详情 | 详情 | |
| (III) | 48740 | C19H21NO4 | 详情 | 详情 | ||
| (IV) | 48741 | 4,7,7-trimethylbicyclo[2.2.1]heptane-2-carboxylic acid | C11H18O2 | 详情 | 详情 | |
| (V) | 48742 | C30H37NO5 | 详情 | 详情 | ||
| (VI) | 48743 | C30H37NO5 | 详情 | 详情 | ||
| (VII) | 48744 | C32H41NO6 | 详情 | 详情 | ||
| (VIII) | 48745 | C21H23NO5 | 详情 | 详情 | ||
| (IX) | 48746 | C33H31NO5S2 | 详情 | 详情 | ||
| (X) | 48747 | C25H21NO5S | 详情 | 详情 | ||
| (XI) | 48748 | 4,5,7,8-tetramethoxy-1H-isochromene-1,3(4H)-dione | C13H14O7 | 详情 | 详情 | |
| (XII) | 48749 | 1-Bromo-2,4,5-trimethoxybenzene | C9H11BrO3 | 详情 | 详情 | |
| (XIII) | 48750 | C32H31NO9 | 详情 | 详情 | ||
| (XIV) | 48751 | C31H29NO9 | 详情 | 详情 | ||
| (XV) | 48752 | C31H27NO10 | 详情 | 详情 | ||
| (XVI) | 48753 | (E)-2-butenyl(triphenyl)phosphonium bromide | C22H22BrP | 详情 | 详情 | |
| (XVII) | 48754 | C35H33NO9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXI)The Sharpless epoxidation of (XV) gives the cis-epoxide (XVI), which by esterification with (-)-camphanic acid (XVII) by means of DEAD and PPh3 under Mitsunobu conditions yields, after chromatographic separation, the trans-epoxide ester (XVIII). The rearrangement of (XVIII) by means of BF3/Et2O in dichloromethane affords the spiro compound (XIX), which is treated with silylated ethyleneglycol and Tms-OTf to provide the ethyleneketal (XX). The hydrolysis if the ester group of (XX) with NaOH, followed by oxidation of the resulting alcohol with DMP, gives the partially protected diketone (XXI). The sulfenylation of (XXI) by means of PhS-SO2Ph and LiHMDS yields the bis-phenyl sulfanyl derivative (XXII), which is treated with TFA and oxidized with MCPBA to afford the phenylsulfinyl compound (XXIII). The cyclization of (XXIII) with the homophthalic anhydride (XXIV) (obtained from trimethoxybromobenzene (XXV)) by means of NaH, followed by methylation of the resulting OH group with Me-I and K2CO3, provides the spiro-hexacyclic compound (XXVI). The selective demethylation of (XXVI) with NaBr and Ts-OH gives the pyridinone derivative (XXVII), which is oxidized with SeO2 to yield the carbaldehyde (XXVIII).
| 【1】 Kita, Y.; et al.; Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A. J Am Chem Soc 2001, 123, 14, 3214. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 48739 | (1R)-10,11-dimethoxy-8-methyl-2,3,4,5-tetrahydro-1H-indeno[5,4-g]isoquinolin-1-ol | C19H21NO3 | 详情 | 详情 | |
| (XVI) | 48740 | C19H21NO4 | 详情 | 详情 | ||
| (XVII) | 48741 | 4,7,7-trimethylbicyclo[2.2.1]heptane-2-carboxylic acid | C11H18O2 | 详情 | 详情 | |
| (XVIII) | 48742 | C30H37NO5 | 详情 | 详情 | ||
| (XIX) | 48743 | C30H37NO5 | 详情 | 详情 | ||
| (XX) | 48744 | C32H41NO6 | 详情 | 详情 | ||
| (XXI) | 48745 | C21H23NO5 | 详情 | 详情 | ||
| (XXII) | 48746 | C33H31NO5S2 | 详情 | 详情 | ||
| (XXIII) | 48747 | C25H21NO5S | 详情 | 详情 | ||
| (XXIV) | 48748 | 4,5,7,8-tetramethoxy-1H-isochromene-1,3(4H)-dione | C13H14O7 | 详情 | 详情 | |
| (XXV) | 48749 | 1-Bromo-2,4,5-trimethoxybenzene | C9H11BrO3 | 详情 | 详情 | |
| (XXVI) | 48750 | C32H31NO9 | 详情 | 详情 | ||
| (XXVII) | 48751 | C31H29NO9 | 详情 | 详情 | ||
| (XXVIII) | 48752 | C31H27NO10 | 详情 | 详情 |