(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one -Drug Synthesis Database

【结构式】

【分子编号】44450

【品名】(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one

【CA登记号】

【分子式】C₁₀H₁₈O₂

【分子量】170.25172

【元素组成】C 70.55% H 10.66% O 18.79%

与该中间体有关的原料药合成路线共 10 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5 合成路线6 合成路线7 合成路线8 合成路线9 合成路线10

合成路线1

该中间体在本合成路线中的序号：(III)

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).

参考文献中间体

合成目标

【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	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：(III)

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).

参考文献中间体

合成目标

【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	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：(XX)

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).

参考文献中间体

合成目标

【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	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：(III)

参考文献中间体

合成目标

【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	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：(XVII)

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).

参考文献中间体

合成目标

【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	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：(XX)

参考文献中间体

合成目标

【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	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7

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【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	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8

该中间体在本合成路线中的序号：(XXXIII)

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).

参考文献中间体

合成目标

【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	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	C₂₉H₅₈O₅Si₂	详情	详情
(XXXI)	44448	2,2-dimethyl-3-oxopentanal	C₇H₁₂O₂	详情	详情
(XXXII)	44449	allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane	C₂₃H₃₉B	详情	详情
(XXXIII)	44450	(5S)-5-hydroxy-4,4-dimethyl-7-octen-3-one	C₁₀H₁₈O₂	详情	详情
(XXXIV)	44451	(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one	C₁₆H₃₂O₂Si	详情	详情
(XXXV)	44452	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanal	C₁₅H₃₀O₃Si	详情	详情
(XXXVI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XXXVII)	27185	(2S)-2-methyl-6-heptenal	C₈H₁₄O	详情	详情

合成路线9

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【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	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10

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【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	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

Extended Information