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【结 构 式】 
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【分子编号】35719 【品名】(9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione 【CA登记号】 |
【 分 子 式 】C39H45NO8 【 分 子 量 】655.78824 【元素组成】C 71.43% H 6.92% N 2.14% O 19.52% |
合成路线1
该中间体在本合成路线中的序号：(XLVIII)The reaction of (XLII) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLIII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLIV). The rearrangement of (XLIV) with Ag2O in DMF/water affords the acetic acid derivative (XLV), which is condensed with indoline (XLVI) by means of EDC and DMAP in dichloromethane to provide the acyl indoline (XLVII). The desilylation of (XLVII) with TFA/water in dichloromethane gives the secondary alcohol (XLVIII), which is oxidized with DMP in dichloromethane to yield the corresponding ketonic compound (XLIX). The dehydrogenation of the indoline group of (XLIX) with chloranil in refluxing toluene affords the corresponding indole derivative (L).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLIII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLIV) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLV) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (XLVI) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (XLVII) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (XLVIII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 | |
| (XLIX) | 35720 | (9S,12S,13S,15R)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H43NO8 | 详情 | 详情 | |
| (L) | 35721 | (9S,12S,13S,15R)-15-[(E)-4-hexenoyl]-9-[2-(1H-indol-1-yl)-2-oxoethyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H41NO8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LII)The silylation at the remaining OH group of (XLIV) with TBDMS-OTf and lutidine in dichloromethane affords the silyl ether (XLV), which is oxidized at the aldehyde group with NaClO2 in tert-butanol/water giving the carboxylic acid (XLVI). The reaction of (XLVI) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLVII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLVIII). The rearrangement of (XLVIII) with Ag2O in DMF/water affords the acetic acid derivative (XLIX), which is condensed with indoline (L) by means of EDC and DMAP in CH2Cl2 to provide the acyl indoline (LI). The desilylation of (LI) with TFA/water in dichloromethane gives the secondary alcohol (LII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLV) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLVI) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLVII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLVIII) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLIX) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (L) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (LI) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(LII)The oxidation of (LII) with DMP in dichloromethane yields the corresponding ketonic compound (LIII), which is dehydrogenated at the indoline group with chloranil in refluxing toluene affording the corresponding indole derivative (LIV). Finally, compound (LIV) is treated with LiOH and NaH2PO4 in THF/water to provide the target compound.
| 【1】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 【2】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 | |
| (LIII) | 35720 | (9S,12S,13S,15R)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H43NO8 | 详情 | 详情 | |
| (LIV) | 35721 | (9S,12S,13S,15R)-15-[(E)-4-hexenoyl]-9-[2-(1H-indol-1-yl)-2-oxoethyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H41NO8 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XLVIII)The reaction of (XLII) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLIII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLIV). The rearrangement of (XLIV) with Ag2O in DMF/water affords the acetic acid derivative (XLV), which is condensed with indoline (XLVI) by means of EDC and DMAP in dichloromethane to provide the acyl indoline (XLVII). The desilylation of (XLVII) with TFA/water in dichloromethane gives the secondary alcohol (XLVIII), which is oxidized with DMP in dichloromethane to yield the corresponding ketonic compound (XLIX). The dehydrogenation of the indoline group of (XLIX) with chloranil in refluxing toluene affords the corresponding indole derivative (L).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLIII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLIV) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLV) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (XLVI) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (XLVII) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (XLVIII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 | |
| (XLIX) | 35720 | (9S,12S,13S,15R)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H43NO8 | 详情 | 详情 | |
| (L) | 35721 | (9S,12S,13S,15R)-15-[(E)-4-hexenoyl]-9-[2-(1H-indol-1-yl)-2-oxoethyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H41NO8 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(LII)The silylation at the remaining OH group of (XLIV) with TBDMS-OTf and lutidine in dichloromethane affords the silyl ether (XLV), which is oxidized at the aldehyde group with NaClO2 in tert-butanol/water giving the carboxylic acid (XLVI). The reaction of (XLVI) with methanesulfonyl chloride and Et3N in THF gives the mixed anhydride (XLVII), which is treated with diazomethane in ethyl ether/THF to yield the diazoketone (XLVIII). The rearrangement of (XLVIII) with Ag2O in DMF/water affords the acetic acid derivative (XLIX), which is condensed with indoline (L) by means of EDC and DMAP in dichloromethane to provide the acyl indoline (LI). The desilylation of (LI) with TFA/water in dichloromethane gives the secondary alcohol (LII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLV) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLVI) | 35714 | C36H50O9Si | 详情 | 详情 | ||
| (XLVII) | 35715 | C39H56O9SSi | 详情 | 详情 | ||
| (XLVIII) | 35716 | C37H50N2O8Si | 详情 | 详情 | ||
| (XLIX) | 35717 | C37H52O9Si | 详情 | 详情 | ||
| (L) | 19652 | indoline | 496-15-1 | C8H9N | 详情 | 详情 |
| (LI) | 35718 | (9S,12S,13S,15R,18R)-18-[[tert-butyl(dimethyl)silyl]oxy]-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C45H59NO8Si | 详情 | 详情 | |
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(LII)The oxidation of (LII) with DMP in dichloromethane yields the corresponding ketonic compound (LIII), which is dehydrogenated at the indoline group with chloranil in refluxing toluene affording the corresponding indole derivative (LIV). Compound (LIV) is treated with LiOH and NaH2PO4 in THF/water to provide the dihydroxylated acetic acid derivative (LV), which is finally cyclized to the target compound by means of methanesulfonic acid in chloroform.
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LII) | 35719 | (9S,12S,13S,15R,18S)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-18-hydroxy-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6-dione | C39H45NO8 | 详情 | 详情 | |
| (LIII) | 35720 | (9S,12S,13S,15R)-9-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-15-[(E)-4-hexenoyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H43NO8 | 详情 | 详情 | |
| (LIV) | 35721 | (9S,12S,13S,15R)-15-[(E)-4-hexenoyl]-9-[2-(1H-indol-1-yl)-2-oxoethyl]-12-[(E)-6-octenyl]-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-diene-4,6,18-trione | C39H41NO8 | 详情 | 详情 | |
| (LV) | 35722 | 2-[(14S,15S)-11-hydroxy-15-[(2R,6E)-2-hydroxy-3-oxo-6-octenyl]-14-[(E)-6-octenyl]-3,5,9-trioxo-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-dien-8-yl]acetic acid | C31H38O10 | 详情 | 详情 |