合成路线1
该中间体在本合成路线中的序号:
(I) The synthesis of intermediate tridecenoic acid (VIII) has been performed as follows: The reaction of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) in ethyl ether gives the chiral beta-hydroxy ketone (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of the double bond of (IV) affords the aldehyde (V), which is oxidized with NaClO2 to the carboxylic acid (VI). Finally, this compound is condensed with 2(S)-methyl-6-heptenal (VII) by means of LDA in THF to provide the intermediate tridecenoic acid (VIII).
【1】
Nicolaou, K.C.; et al.; The olefin metathesis approach to epothilone A and its analogues. J Am Chem Soc 1997, 119, 34, 7960.
|
【2】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(VI) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
(VII) |
27185 |
(2S)-2-methyl-6-heptenal
|
|
C8H14O |
详情 |
详情
|
(VIII) |
44453 |
(3S,6R,7S,8S)-3-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid
|
|
C23H44O5Si |
详情 |
详情
|
合成路线2
该中间体在本合成路线中的序号:
(I) The oxoacid intermediate (VI) has been obtained as follows: The condensation of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) gives the chiral 5(S)-hydroxy-4,4-dimethyl-7-octen-3-one (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of (IV) in dichloromethane affords the aldehyde (V), which is finally oxidized with NaClO2 in tert-butanol/water to provide the target oxoacid intermediate (VI).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(VI) |
43162 |
(4-methoxybutylidene)(triphenyl)phosphorane; methyl 4-(triphenylphosphoranylidene)butyl ether
|
|
C23H25OP |
详情 |
详情
|
合成路线3
该中间体在本合成路线中的序号:
(XIX) The condensation of 2,2-dimethyl-3-oxopentanal (XIX) with the chiral borane (V) in ethyl ether gives the chiral hydroxyketone (XX), which is treated with Tbdms-OTf and lutidine in dichloromethane to yield the silyl ether (XXI). Ozonolysis of the terminal double bond of (XXI) affords the aldehyde (XXII), which is oxidized to the carboxylic acid (XXIII) with NaClO2. The condensation of (XXIII) with the reported intermediate aldehyde (XVIII) by means of LDA in THF provides the hydroxyacid (XXIV), which is silylated with Tbdms-OTf and lutidine in dichloromethane to furnish the fully silylated compound (XXV). The hydrolysis of the silyl ester of (XXV) with K2CO3 in methanol gives the carboxylic acid (XXVI), which is selectively desilylated with TBAF in THF to yield the hydroxyacid (XXVII).The macrolactonization of (XXVII) by treatment with 2,4,6-trichlorobenzoyl chloride and TEA in THF, followed by a treatment with DMAP in toluene, affords the silylated macrolactone (XXVIII).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(V) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(XVIII) |
40829 |
(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal
|
|
C24H41NO2SSi |
详情 |
详情
|
(XIX) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(XX) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(XXI) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(XXII) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(XXIII) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
(XXIV) |
46118 |
(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C39H71NO6SSi2 |
详情 |
详情
|
(XXV) |
46119 |
tert-butyl(dimethyl)silyl (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate
|
|
C51H99NO6SSi4 |
详情 |
详情
|
(XXVI) |
40834 |
(3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C45H85NO6SSi3 |
详情 |
详情
|
(XXVII) |
40835 |
(3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C39H71NO6SSi2 |
详情 |
详情
|
(XXVIII) |
40836 |
(4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione
|
|
C39H69NO5SSi2 |
详情 |
详情
|
合成路线4
该中间体在本合成路线中的序号:
(I) The oxoacid intermediate (VI) has been obtained as follows: The condensation of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) gives the chiral 5(S)-hydroxy-4,4-dimethyl-7-octen-3-one (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of (IV) in dichloromethane affords the aldehyde (V), which is finally oxidized with NaClO2 in tert-butanol/water to provide the target oxoacid intermediate (VI).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(VI) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
合成路线5
该中间体在本合成路线中的序号:
(XVI) Synthesis of intermediate ketone (XVIII): The reaction of 2,2-dimethyl-3-oxopentanal (XVI) with (+)-allyldi(isopinocampheyl)borane in ethyl ether gives the chiral beta-hydroxyketone (XVII), which is silylated with Tbdms-OTf and lutidine in dichloromethane to afford the desired intermediate ketone (XVIII).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(XVI) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(XVII) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(XVIII) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
合成路线6
该中间体在本合成路线中的序号:
(II) The intermediate carboxylic acid (V) has been obtained as follows: The reaction of the chiral auxiliary oxazolidinone (I) with the oxoaldehyde (II) by means of Bu2B-OTf, DIEA and Raney Ni in dichloromethane gives the oxazolidide (III), which is treated with Tbdms-OTf, yielding the silyl ether (IV), which is easily purified. Elimination of the auxiliary with LiOH and H2O2 in THF/water affords the target carboxylic acid (V).
【1】
Valluri, M.; et al.; Total synthesis of epothilone B. Org Lett 2001, 3, 23, 3607.
|
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) |
52571 |
3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one
|
|
C34H50N2O5SSi |
详情 |
详情
|
(II) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(III) |
52572 |
4-(1-methylethyl)-3-[2-(methylsulfanyl)acetyl]-1,3-oxazolidin-2-one
|
|
C9H15NO3S |
详情 |
详情
|
(IV) |
52573 |
3-hydroxy-4,4-dimethyl-1-[4-(1-methylethyl)-2-oxo-1,3-oxazolidin-3-yl]-1,5-heptanedione
|
|
C15H25NO5 |
详情 |
详情
|
(V) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
合成路线7
该中间体在本合成路线中的序号:
(I) The aldol condensation of 2,2-dimethyl-3-oxopentanal (I) with acetylsultam (II) by means of Et3B/OTf and DIEA gives the aldol adduct (III), which is treated with Tbdms-OTf to yield the silyl ether (IV). The TiCl4 catalyzed aldol reaction between ketone (IV) with the intermediate aldehyde (V) affords the aldol adduct (VI), which is treated with Tbdms-OTf to provide the silylated adduct (VII). Finally the cleavage of the sultam group of (VII) by means of LiO2H furnishes the already known carboxylic acid intermediate (VIII)
【1】
Altmann, K.-H.; et al.; The total synthesis and biological assessment of trans-epothilone A. Helv Chim Acta 2002, 85, 11, 4086.
|
【2】
Koch, G.; Loiseleur, O.; Fuentes, D.; Jantsch, A.; Altmann, K.-H.; Diastereoselective titanium enolate aldol reaction for the total synthesis of epothilones. Org Lett 2002, 4, 22, 3811.
|
【3】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
62591 |
4-acetyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione
|
|
C10H15NO3S |
详情 |
详情
|
(III) |
62592 |
4-[(3S)-3-hydroxy-4,4-dimethyl-5-oxoheptanoyl]-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione
|
|
C17H27NO5S |
详情 |
详情
|
(IV) |
62593 |
4-((3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-dimethyl-5-oxoheptanoyl)-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione
|
|
C23H41NO5SSi |
详情 |
详情
|
(V) |
62594 |
(2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-[(triethylsilyl)oxy]-6,10-undecadienal
|
|
C24H41NO2SSi |
详情 |
详情
|
(VI) |
62595 |
4-{(3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-[(triethylsilyl)oxy]-12,16-heptadecadienoyl}-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione
|
|
C47H82N2O7S2Si2 |
详情 |
详情
|
(VII) |
62596 |
4-{(3S,6R,7S,8S,12Z,15S,16E)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-[(triethylsilyl)oxy]-12,16-heptadecadienoyl}-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione
|
|
C53H96N2O7S2Si3 |
详情 |
详情
|
(VIII) |
62597 |
(3S,6R,7S,8S,12Z,15S,16E)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-[(triethylsilyl)oxy]-12,16-heptadecadienoic acid
|
|
C45H85NO6SSi3 |
详情 |
详情
|
合成路线8
该中间体在本合成路线中的序号:
(XIX) The condensation of 2,2-dimethyl-3-oxopentanal (XIX) with the chiral borane (V) in ethyl ether gives the chiral hydroxyketone (XX), which is treated with Tbdms-OTf and lutidine in dichloromethane to yield the silyl ether (XXI). Ozonolysis of the terminal double bond of (XXI) affords the aldehyde (XXII), which is oxidized to the carboxylic acid (XXIII) with NaClO2. The condensation of (XXIII) with the reported intermediate aldehyde (XVIII) by means of LDA in THF provides the hydroxyacid (XXIV), which is silylated with Tbdms-OTf and lutidine in dichloromethane to furnish the fully silylated compound (XXV). The hydrolysis of the silyl ester of (XXV) with K2CO3 in methanol gives the carboxylic acid (XXVI), which is selectively desilylated with TBAF in THF to yield the hydroxyacid (XXVII).The macrolactonization of (XXVII) by treatment with 2,4,6-trichlorobenzoyl chloride and TEA in THF, followed by a treatment with DMAP in toluene, affords the silylated macrolactone (XXVIII), which is finally deprotected with TFA in dichloromethane to provide the target epothilone D.
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(V) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(XVIII) |
40829 |
(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal
|
|
C24H41NO2SSi |
详情 |
详情
|
(XIX) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(XX) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(XXI) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(XXII) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(XXIII) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
(XXIV) |
46118 |
(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C39H71NO6SSi2 |
详情 |
详情
|
(XXV) |
46119 |
tert-butyl(dimethyl)silyl (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate
|
|
C51H99NO6SSi4 |
详情 |
详情
|
(XXVI) |
40834 |
(3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C45H85NO6SSi3 |
详情 |
详情
|
(XXVII) |
40835 |
(3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid
|
|
C39H71NO6SSi2 |
详情 |
详情
|
(XXVIII) |
40836 |
(4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione
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|
C39H69NO5SSi2 |
详情 |
详情
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合成路线9
该中间体在本合成路线中的序号:
(I) The oxoacid intermediate (VI) has been obtained as follows: The condensation of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) gives the chiral 5(S)-hydroxy-4,4-dimethyl-7-octen-3-one (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of (IV) in dichloromethane affords the aldehyde (V), which is finally oxidized with NaClO2 in tert-butanol/water to provide the target oxoacid intermediate (VI).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
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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) |
44448 |
2,2-dimethyl-3-oxopentanal
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|
C7H12O2 |
详情 |
详情
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(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
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|
C23H39B |
详情 |
详情
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(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
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|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
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|
C16H32O2Si |
详情 |
详情
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(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
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|
C15H30O3Si |
详情 |
详情
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(VI) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
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|
C15H30O4Si |
详情 |
详情
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合成路线10
该中间体在本合成路线中的序号:
(XXXI) The reaction of 2,2-dimethyl-3-oxopentanal (XXXI) with (+)-diisopinocampheyl(allyl)borane (XXXII) in ethyl ether gives the chiral beta-hydroxy ketone (XXXIII), which is protected with Tbdms-OTf to yield the silyl ether (XXXIV). The ozonolysis of the double bond of (XXXIV) affords the aldehyde (XXXV), which is oxidized with NaClO2 to the carboxylic acid (XXXVI). Finally, this compound is condensed with 2(S)-methyl-6-heptenal (VII) by means of LDA in THF to provide the intermediate tridecenoic acid (XII).
【1】
Nicolaou, K.C.; et al.; The olefin metathesis approach to epothilone A and its analogues. J Am Chem Soc 1997, 119, 34, 7960.
|
【2】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
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中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(XII) |
44438 |
(3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid
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|
C29H58O5Si2 |
详情 |
详情
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(XXXI) |
44448 |
2,2-dimethyl-3-oxopentanal
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|
C7H12O2 |
详情 |
详情
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(XXXII) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
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|
C23H39B |
详情 |
详情
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(XXXIII) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
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|
C10H18O2 |
详情 |
详情
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(XXXIV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
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|
C16H32O2Si |
详情 |
详情
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(XXXV) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
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|
C15H30O3Si |
详情 |
详情
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(XXXVI) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
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(XXXVII) |
27185 |
(2S)-2-methyl-6-heptenal
|
|
C8H14O |
详情 |
详情
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合成路线11
该中间体在本合成路线中的序号:
(I) The synthesis of intermediate tridecenoic acid (VIII) has been performed as follows: The reaction of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) in ethyl ether gives the chiral beta-hydroxy ketone (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of the double bond of (IV) affords the aldehyde (V), which is oxidized with NaClO2 to the carboxylic acid (VI). Finally, this compound is condensed with 2(S)-methyl-6-heptenal (VII) by means of LDA in THF to provide the intermediate tridecenoic acid (VIII).
【1】
Nicolaou, K.C.; et al.; The olefin metathesis approach to epothilone A and its analogues. J Am Chem Soc 1997, 119, 34, 7960.
|
【2】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(VI) |
43166 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid
|
|
C15H30O4Si |
详情 |
详情
|
(VII) |
27185 |
(2S)-2-methyl-6-heptenal
|
|
C8H14O |
详情 |
详情
|
(VIII) |
44453 |
(3S,6R,7S,8S)-3-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid
|
|
C23H44O5Si |
详情 |
详情
|
合成路线12
该中间体在本合成路线中的序号:
(I) The oxoacid intermediate (VI) has been obtained as follows: The condensation of 2,2-dimethyl-3-oxopentanal (I) with (+)-diisopinocampheyl(allyl)borane (II) gives the chiral 5(S)-hydroxy-4,4-dimethyl-7-octen-3-one (III), which is protected with Tbdms-OTf, yielding the silyl ether (IV). The ozonolysis of (IV) in dichloromethane affords the aldehyde (V), which is finally oxidized with NaClO2 in tert-butanol/water to provide the target oxoacid intermediate (VI).
【1】
Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.
|
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) |
44448 |
2,2-dimethyl-3-oxopentanal
|
|
C7H12O2 |
详情 |
详情
|
(II) |
44449 |
allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane
|
|
C23H39B |
详情 |
详情
|
(III) |
44450 |
(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one
|
|
C10H18O2 |
详情 |
详情
|
(IV) |
44451 |
(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one
|
|
C16H32O2Si |
详情 |
详情
|
(V) |
44452 |
(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal
|
|
C15H30O3Si |
详情 |
详情
|
(VI) |
43162 |
(4-methoxybutylidene)(triphenyl)phosphorane; methyl 4-(triphenylphosphoranylidene)butyl ether
|
|
C23H25OP |
详情 |
详情
|