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【结 构 式】 
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【分子编号】36852 【品名】methyl (2S,3S,6R)-6-(acetoxy)-3-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C15H18O5 【 分 子 量 】278.30492 【元素组成】C 64.74% H 6.52% O 28.74% |
合成路线1
该中间体在本合成路线中的序号：(XXX)The enzymatic resolution of the tricyclic carboxylate (XXIX) with chiralzyme L-2 and vinyl acetate gives the monoacetate (XXX) and the dihydroxy compound (XXXI) that are easily separated. The monosilylation of the less hindered OH group of (XXXI) with TBDMS-Cl and imidazole in DMF gives the monosilylated compound (XXXII), which is acylated with acetyl chloride, TEA and DMAP in dichloromethane yielding the monoacetate (XXXIII). The desilylation of (XXXIII) with TBAF in THF affords the secondary alcohol (XXXIV), which is oxidized with ammonium formate and PdCl2(PPh3)2 in acetonitrile to give the unsaturated ketone (XXXV). The epoxidation of the double bond of (XXXV) with H2O2 and Triton B in THF yields the ketoepoxide (XXXVI), which is reduced with NaBH4 in methanol to the epoxy alcohol (XXXVII). The esterification of (XXXVII) with benzoyl chloride affords the benzoate (XXXVIII), which is submitted to thermolysis at 300 C in diphenyl ether to provide the cyclohexenecarboxylate (XXXIX).The reaction of (XXXIX) with BF3 ethearate in toluene gives, through the nonisolable oxonium intermediate (XL), the monobenzoate (XLI), which is debenzoylated with K2CO3 in methanol to provide the methyl ester (XLII) of the target compound. Finally, this compound is hydrolyzed with KOH in THF.
| 【1】 Yoshida, N.; Ogasawara, K.; An enatioconvergent route to (-)-shikimic acid via a palladium-mediated elimination reaction. Org Lett 2000, 2, 10, 1461. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX),(XXXI) | 36851 | methyl (2R,3R,6S)-3,6-dihydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C13H16O4 | 详情 | 详情 | |
| (XIV) | 29907 | (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid; Shikimic acid | 138-59-0 | C7H10O5 | 详情 | 详情 |
| (XXX) | 36852 | methyl (2S,3S,6R)-6-(acetoxy)-3-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C15H18O5 | 详情 | 详情 | |
| (XXXII) | 36853 | methyl (2R,3R,6S)-6-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C19H30O4Si | 详情 | 详情 | |
| (XXXIII) | 36854 | methyl (2R,3R,6S)-3-(acetoxy)-6-[[tert-butyl(dimethyl)silyl]oxy]tricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C21H32O5Si | 详情 | 详情 | |
| (XXXIV) | 36855 | methyl (2R,3R,6S)-3-(acetoxy)-6-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C15H18O5 | 详情 | 详情 | |
| (XXXV) | 36856 | methyl (2R)-6-oxotricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C13H14O3 | 详情 | 详情 | |
| (XXXVI) | 36857 | methyl (2R,4R,6R)-7-oxo-5-oxatetracyclo[7.2.1.0(2,8).0(4,6)]dodec-10-ene-2-carboxylate | C13H14O4 | 详情 | 详情 | |
| (XXXVII) | 36858 | methyl (2R,4R,6S,7R)-7-hydroxy-5-oxatetracyclo[7.2.1.0(2,8).0(4,6)]dodec-10-ene-2-carboxylate | C13H16O4 | 详情 | 详情 | |
| (XXXVIII) | 36859 | methyl (2R,4R,6R,7R)-7-(benzoyloxy)-5-oxatetracyclo[7.2.1.0(2,8).0(4,6)]dodec-10-ene-2-carboxylate | C20H20O5 | 详情 | 详情 | |
| (XXXIX) | 36860 | methyl (1R,5R,6R)-5-(benzoyloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate | C15H14O5 | 详情 | 详情 | |
| (XL) | 36861 | C15H14BF3O5 | 详情 | 详情 | ||
| (XLI) | 36862 | (1R,5R,6S)-5,6-dihydroxy-3-(methoxycarbonyl)-2-cyclohexen-1-yl benzoate | C15H16O6 | 详情 | 详情 | |
| (XLII) | 29908 | methyl (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate | C8H12O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXX)The enzymatic resolution of the tricyclic carboxylate (XXIX) with chiralzyme L-2 and vinyl acetate gives the monoacetate (XXX) and the dihydroxy compound (XXXI) that are easily separated. The hydrolysis of the acetate (XXX) with K2CO3 in methanol yields the diol (XLIII), which silylated with TBDMS-Cl and imidazole at the less hindered OH affording the silyl ether (XLIV). The acetylation of (XLIV) with acetyl chloride, TEA and DMAP gives the acetate (XLV), which is desilylated with TBAF in THF yielding the alcohol (XLVI). The oxidation of (XLVI) with ammonium formate and PdCl2(PPh3)2 in refluxing acetonitrile affords the ketone (XLVII), which is epoxidized with H2O2 and Triton B in THF providing the ketoepoxide (XLVIII). The thermolysis of (XLVIII) at 300 C in diphenyl ether gives the epoxycyclohexenone (II), which is reduced with NaBH4 and CeCl3 in methanol yielding a mixture of the two diastereomeric alcohols (L) and (LI) that are separated by column chromatography. The desired alcohol (LI) is treated with refluxing 80% AcOH to afford the methyl ester (XLII) of the target compound. Finally, this compound is hydrolyzed with KOH in THF. The undesired diastereomeric alcohol (L) is recycled to epoxyketone (II) by oxidation with tetrapropylammonium perruthenate (TPAP) and NMMO.
| 【1】 Yoshida, N.; Ogasawara, K.; An enatioconvergent route to (-)-shikimic acid via a palladium-mediated elimination reaction. Org Lett 2000, 2, 10, 1461. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX),(XXXI) | 36851 | methyl (2R,3R,6S)-3,6-dihydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C13H16O4 | 详情 | 详情 | |
| (IL) | 36865 | methyl (1S,6S)-5-oxo-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate | C8H8O4 | 详情 | 详情 | |
| (XIV) | 29907 | (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid; Shikimic acid | 138-59-0 | C7H10O5 | 详情 | 详情 |
| (XXX) | 36852 | methyl (2S,3S,6R)-6-(acetoxy)-3-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C15H18O5 | 详情 | 详情 | |
| (XLII) | 29908 | methyl (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate | C8H12O5 | 详情 | 详情 | |
| (XLIII) | 36867 | methyl (2S,3S,6R)-3,6-dihydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C13H16O4 | 详情 | 详情 | |
| (XLIV) | 36868 | methyl (2S,3S,6R)-6-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C19H30O4Si | 详情 | 详情 | |
| (XLV) | 36869 | methyl (2S,3S,6R)-3-(acetoxy)-6-[[tert-butyl(dimethyl)silyl]oxy]tricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C21H32O5Si | 详情 | 详情 | |
| (XLVI) | 36870 | methyl (2S,3S,6R)-3-(acetoxy)-6-hydroxytricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C15H18O5 | 详情 | 详情 | |
| (XLVII) | 36863 | methyl (2S,3S)-3-(acetoxy)-6-oxotricyclo[6.2.1.0(2,7)]undeca-4,9-diene-2-carboxylate | C15H16O5 | 详情 | 详情 | |
| (XLVIII) | 36864 | methyl (2S,3R,4R,6S)-3-(acetoxy)-7-oxo-5-oxatetracyclo[7.2.1.0(2,8).0(4,6)]dodec-10-ene-2-carboxylate | C15H16O6 | 详情 | 详情 | |
| (L) | 36866 | methyl (1S,5S,6R)-5-hydroxy-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate | C8H10O4 | 详情 | 详情 | |
| (LI) | 29912 | methyl (1S,5R,6R)-5-hydroxy-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate | C8H10O4 | 详情 | 详情 |