[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide -Drug Synthesis Database

【结构式】

【分子编号】44459

【品名】[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide

【CA登记号】

【分子式】C₃₄H₄₃INOPSSi

【分子量】699.751292

【元素组成】C 58.36% H 6.19% I 18.14% N 2% O 2.29% P 4.43% S 4.58% Si 4.01%

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：(XVI)

The intermediate phosphonium salt (XVI) has been obtained as follows: The reduction of 2-methylthiazole-4-carboxylic acid ethyl ester (VII) with DIBAL in dichloromethane gives the corresponding aldehyde (VIII), which is condensed with the phosphorane (IX) in refluxing benzene to yield 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (X). The allylation of (X) with (+)-diisopinocampheyl(allyl)borane (II) affords the chiral secondary alcohol (XI), which is protected with Tbdms-Cl and imidazole in DMF, providing the silyl ether (XII). The oxidation of the terminal double bond of (XII) with OsO4 and Pb(OAc)4 in THF/tert-butanol/water gives rise to the aldehyde (XIII), which is reduced with NaBH4 in methanol to give the corresponding primary alcohol (XIV). The reaction of (XIV) with I2, PPh3 and imidazole in ethyl ether/acetonitrile yields the expected iodo derivative (XV), which is finally condensed with PPh3 at 100 C to afford the desired intermediate phosphonium salt (XVI).

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	CAS号	分子式	供应商	用于合成
(II)	44449	allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane		C₂₃H₃₉B	详情	详情
(VII)	44454	ethyl 2-methyl-1,3-thiazole-4-carboxylate	6436-59-5	C₇H₉NO₂S	详情	详情
(VIII)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(IX)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether		C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal		C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	40821	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol		C₁₆H₂₉NO₂SSi	详情	详情
(XV)	44458	tert-butyl(dimethyl)silyl (1S,2E)-1-(2-iodoethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole		C₁₆H₂₈INOSSi	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide		C₃₄H₄₃INOPSSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Assembly of the final product: The condensation of SAMP hydrazone (XVII) with 4-(benzyloxy)butyl iodide (XVIII) by means of LDA in THF gives the chiral 2-methylhexanal hydrazone (XIX), which is ozonolyzed in dichloromethane, yielding the free aldehyde (XX). The reduction of (XX) with NaBH4 in methanol affords the corresponding alcohol (XXI), which is protected with Tbdms-Cl and TEA in dichloromethane, providing the silyl ether (XXII). The hydrogenolysis of (XXII) with H2 over Pd/C in THF furnishes the alcohol (XXIII), which is oxidized to the aldehyde (XXIV) with oxalyl chloride, DMSO and TEA in dichloromethane. The condensation of aldehyde (XXIV) with the intermediate phosphonium salt (XVI) by means of NaHMDS in THF gives the silylated diol (XXV), which is selectively monodesilylated with CSA in dichloromethane/methanol to yield the primary alcohol (XXVI). The oxidation of (XXVI) with SO3/pyridine, DMSO and TEA in dichloromethane affords the corresponding aldehyde (XXVII), which is condensed with the oxoacid intermediate (VI) by means of LDA in THF to provide the linear heptadecadienoic acid (XXVIII) as a diastereomeric mixture.

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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	44467	4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienyl ether	C₂₉H₅₅NO₂SSi₂	详情	详情
(XXVI)	44468	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₃H₄₁NO₂SSi	详情	详情
(XXVII)	44469	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₃H₃₉NO₂SSi	详情	详情
(XXVIII)	44470	(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₈H₆₉NO₆SSi₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVI)

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	CAS号	分子式	供应商	用于合成
(II)	44449	allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane		C₂₃H₃₉B	详情	详情
(VII)	44454	ethyl 2-methyl-1,3-thiazole-4-carboxylate	6436-59-5	C₇H₉NO₂S	详情	详情
(VIII)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(IX)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether		C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal		C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	40821	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol		C₁₆H₂₉NO₂SSi	详情	详情
(XV)	44458	tert-butyl(dimethyl)silyl (1S,2E)-1-(2-iodoethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole		C₁₆H₂₈INOSSi	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide		C₃₄H₄₃INOPSSi	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XVI)

Assembly of the final product: The condensation of SAMP hydrazone (XVII) with 4-(benzyloxy)butyl iodide (XVIII) by means of LDA in THF gives the chiral 2-methylhexanal hydrazone (XIX), which is ozonolyzed in dichloromethane, yielding the free aldehyde (XX). The reduction of (XX) with NaBH4 in methanol affords the corresponding alcohol (XXI), which is protected with Tbdms-Cl and TEA in dichloromethane, providing the silyl ether (XXII). The hydrogenolysis of (XXII) with H2 over Pd/C in THF furnishes the alcohol (XXIII), which is oxidized to the aldehyde (XXIV) with oxalyl chloride, DMSO and TEA in dichloromethane. The methylation of aldehyde (XXIV) with Me-MgBr in THF gives the secondary alcohol (XXV), which is oxidized with tetrapropylammonium perruthenate (TPAP) in dichloromethane, yielding the methyl ketone (XXVI). The condensation of ketone (XXVI) with the intermediate phosphonium salt (XVI) by means of NaHMDS in THF gives the silylated diol (XXVII), which is selectively monodesilylated with CSA in dichloromethane/methanol to yield the primary alcohol (XXVIII). The oxidation of (XXVIII) with SO3/pyridine, DMSO and TEA in dichloromethane affords the corresponding aldehyde (XXIX), which is condensed with the oxoacid intermediate (VI) by means of LDA in THF to provide the linear heptadecadienoic acid (XXX) as a diastereomeric mixture that is separated at the carboxylic acid (XXXII) step.

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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	46120	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanol	C₁₄H₃₂O₂Si	详情	详情
(XXVI)	46121	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanone	C₁₄H₃₀O₂Si	详情	详情
(XXVII)	40827	tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole	C₃₀H₅₇NO₂SSi₂	详情	详情
(XXVIII)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(XXIX)	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
(XXX)	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

合成路线5

该中间体在本合成路线中的序号：(I)

The condensation of the phosphonium salt (I) with the ketone (II) by means of NaHMDS in THF gives the diene (III), which is selectively monodeprotected with CSA in methanol/dichloromethane to yield the primary alcohol (IV). The oxidation of (IV) with SO3/pyridine affords the corresponding aldehyde (V), which is condensed with the ketoacid (VI) by means of LDA in THF to provide the heptadienoic acid (VII). The protection of the OH group of (VII) y means of Tbdms-OTf and lutidine in dichloromethane gives the fully silylated compound (VIII), which is selectively monodeprotected with TBAF in THF to yield the hydroxyacid (IX). The macrolactonization of (IX) by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF affords the macrolactone (X), which is deprotected with TFA in dichloromethane to provide the precursor (XI). Finally, this compound is epoxidized by means of methyl(trifluoromethyl)dioxirane in acetonitrile to furnish the target epothilone B.

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; Synthesis of epothilones A and B in solid and solution phase. Nature 1997, 387, 6630, 268.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(II)	46121	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanone	C₁₄H₃₀O₂Si	详情	详情
(III)	40827	tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole	C₃₀H₅₇NO₂SSi₂	详情	详情
(IV)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(V)	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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(VII)	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
(VIII)	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
(IX)	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
(X)	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
(XI)	40837	(4S,7R,8S,9S,16S)-4,8-dihydroxy-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	C₂₇H₄₁NO₅S	详情	详情
(XII)	31501	3,3-dimethyl-1,2-dioxirane	C₃H₆O₂	详情	详情

合成路线6

该中间体在本合成路线中的序号：(XVI)

The intermediate phosphonium salt (XVI) has been obtained as follows: The reduction of 2-methylthiazole-4-carboxylic acid ethyl ester (VII) with DIBAL in dichloromethane gives the corresponding aldehyde (VIII), which is condensed with the phosphorane (IX) in refluxing benzene to yield 2-methyl-3-(2-methylthiazol-4-yl)-2(E)-propenal (X). The allylation of (X) with (+)-diisopinocampheyl(allyl)borane (II) affords the chiral secondary alcohol (XI), which is protected with Tbdms-Cl and imidazole in DMF to provide the silyl ether (XII). The oxidation of the terminal double bond of (XII) with OsO4 and Pb(OAc)4 in THF/tert-butanol/water gives rise to the aldehyde (XIII), which is reduced with NaBH4 in methanol to give the corresponding primary alcohol (XIV). The reaction of (XIV) with I2, PPh3 and imidazole in ethyl ether/acetonitrile yields the expected iodo derivative (XV), which is finally condensed with PPh3 at 100 C to afford the desired intermediate phosphonium salt (XVI).

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	CAS号	分子式	供应商	用于合成
(II)	44449	allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane		C₂₃H₃₉B	详情	详情
(VII)	44454	ethyl 2-methyl-1,3-thiazole-4-carboxylate	6436-59-5	C₇H₉NO₂S	详情	详情
(VIII)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(IX)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether		C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal		C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	40821	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol		C₁₆H₂₉NO₂SSi	详情	详情
(XV)	44458	tert-butyl(dimethyl)silyl (1S,2E)-1-(2-iodoethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole		C₁₆H₂₈INOSSi	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide		C₃₄H₄₃INOPSSi	详情	详情

合成路线7

该中间体在本合成路线中的序号：(XVI)

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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	46120	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanol	C₁₄H₃₂O₂Si	详情	详情
(XXVI)	46121	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanone	C₁₄H₃₀O₂Si	详情	详情
(XXVII)	40827	tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole	C₃₀H₅₇NO₂SSi₂	详情	详情
(XXVIII)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(XXIX)	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
(XXX)	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

合成路线8

该中间体在本合成路线中的序号：(I)

The condensation of the phosphonium salt (I) with the ketone (II) by means of NaHMDS in THF gives the diene (III), which is selectively monodeprotected with CSA in methanol/dichloromethane to yield the primary alcohol (IV). The oxidation of (IV) with SO3/pyridine affords the corresponding aldehyde (V), which is condensed with the ketoacid (VI) by means of LDA in THF to provide the heptadienoic acid (VII). The protection of the OH group of (VII) y means of Tbdms-OTf and lutidine in dichloromethane gives the fully silylated compound (VIII), which is selectively monodeprotected with TBAF in THF to yield the hydroxyacid (IX). The macrolactonization of (IX) by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF affords the macrolactone (X), which is finally deprotected with TFA in dichloromethane to provide the target epothilone D.

参考文献中间体

合成目标

【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(II)	46121	(6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanone	C₁₄H₃₀O₂Si	详情	详情
(III)	40827	tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole	C₃₀H₅₇NO₂SSi₂	详情	详情
(IV)	40828	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₄H₄₃NO₂SSi	详情	详情
(V)	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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(VII)	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
(VIII)	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
(IX)	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
(X)	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9

该中间体在本合成路线中的序号：(XVI)

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	CAS号	分子式	供应商	用于合成
(II)	44449	allyl[bis[(1R,2S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane		C₂₃H₃₉B	详情	详情
(VII)	44454	ethyl 2-methyl-1,3-thiazole-4-carboxylate	6436-59-5	C₇H₉NO₂S	详情	详情
(VIII)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(IX)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(X)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(XI)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(XII)	44444	4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether		C₁₇H₂₉NOSSi	详情	详情
(XIII)	40822	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal		C₁₆H₂₇NO₂SSi	详情	详情
(XIV)	40821	(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol		C₁₆H₂₉NO₂SSi	详情	详情
(XV)	44458	tert-butyl(dimethyl)silyl (1S,2E)-1-(2-iodoethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole		C₁₆H₂₈INOSSi	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide		C₃₄H₄₃INOPSSi	详情	详情

合成路线10

该中间体在本合成路线中的序号：(XVI)

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
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	44467	4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienyl ether	C₂₉H₅₅NO₂SSi₂	详情	详情
(XXVI)	44468	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₃H₄₁NO₂SSi	详情	详情
(XXVII)	44469	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₃H₃₉NO₂SSi	详情	详情
(XXVIII)	44470	(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₈H₆₉NO₆SSi₂	详情	详情

Extended Information