(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 -Drug Synthesis Database

【结构式】

【分子编号】35718

【品名】(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

【CA登记号】

【分子式】C₄₅H₅₉NO₈Si

【分子量】770.0509

【元素组成】C 70.19% H 7.72% N 1.82% O 16.62% Si 3.65%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(XLVII)

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).

参考文献中间体

合成目标

【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：(LI)

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).

参考文献中间体

合成目标

【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：(XLVII)

参考文献中间体

合成目标

【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4

该中间体在本合成路线中的序号：(LI)

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).

参考文献中间体

合成目标

【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

Extended Information