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【结 构 式】 
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【分子编号】31501 【品名】3,3-dimethyl-1,2-dioxirane 【CA登记号】 |
【 分 子 式 】C3H6O2 【 分 子 量 】74.07944 【元素组成】C 48.64% H 8.16% O 43.2% |
合成路线1
该中间体在本合成路线中的序号：(XI)The methylation of the homoallyl alcohol (I) with methyl iodide and NaH in DMF gives the methyl ether (II), which is oxidized with O3, yielding the aldehyde (III). The diastereoselective allylation of (III) with the chiral borane (IV) in ethyl ether affords the homoallyl alcohol (V), which is epoxidized to the epoxide (VI). The cleavage of the epoxide (VI) with trichloromethyl carbonate provides the cyclic carbonate (VII), which is protected with Troc-Cl and pyridine and then oxidized with NaIO4, furnishing the aldehyde (VIII). The asymetric allylation of (VIII) with the chiral boronate (IX) gives the new homoallyl alcohol (X), which is treated with dimethyldioxirane (XI) to yield the epoxide (XII). Elimination of the Troc- group of (XII) with Zn/HOAc, followed by selective silylation with Tbdps-Cl and imidazole, affords the cyclized tetrahydropyran derivative (XIII), which is cyclized with P2O5 and formaldehyde, and oxidized with CrO3 and sulfuric acid to provide the bicyclic carboxylic acid (XIV).
| 【1】 Roush, W.R.; Marron, T.G.; Diastereoselective synthesis of N-benzoyl mycalamine, the fully elaborated trioxadecalin nucleus of mycalamide A. Control of the key N-acyl aminal stereocenter via carbamate acylation. Tetrahedron Lett 1995, 36, 10, 1581. |
| 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) | 43431 | (1S)-1-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3-buten-1-ol | C13H24O3 | 详情 | 详情 | |
| (II) | 43432 | (4R)-2,2-diethyl-4-[(1S)-1-methoxy-2,2-dimethyl-3-butenyl]-1,3-dioxolane; (1S)-1-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3-butenyl methyl ether | C14H26O3 | 详情 | 详情 | |
| (III) | 43433 | (3S)-3-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-3-methoxy-2,2-dimethylpropanal | C13H24O4 | 详情 | 详情 | |
| (IV) | 43434 | allyl[bis[(1R,2R,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane | C23H39B | 详情 | 详情 | |
| (V) | 43435 | (1S,3R)-1-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-1-methoxy-2,2-dimethyl-5-hexen-3-ol | C16H30O4 | 详情 | 详情 | |
| (VI) | 43436 | (2R,4S)-4-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-4-methoxy-3,3-dimethyl-1-[(2S)oxiranyl]-2-butanol | C16H30O5 | 详情 | 详情 | |
| (VII) | 43437 | (4S)-4-[(2R,4S)-4-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-2-hydroxy-4-methoxy-3,3-dimethylbutyl]-1,3-dioxolan-2-one | C17H30O7 | 详情 | 详情 | |
| (VIII) | 43438 | (1R,3S)-3-methoxy-2,2-dimethyl-4-oxo-1-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]butyl 2,2,2-trichloroethyl carbonate | C14H19Cl3O8 | 详情 | 详情 | |
| (IX) | 43439 | diethyl (4R,5R)-2-[(E)-3-(trimethylsilyl)-2-propenyl]-1,3,2-dioxaborolane-4,5-dicarboxylate | C14H25BO6Si | 详情 | 详情 | |
| (X) | 43440 | (1R,3S,4R,5S)-4-hydroxy-3-methoxy-2,2-dimethyl-1-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]-5-[(trimethylsilyl)oxy]-6-heptenyl 2,2,2-trichloroethyl carbonate | C20H33Cl3O9Si | 详情 | 详情 | |
| (XI) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 | |
| (XII) | 43441 | (1R,3S,4R)-4-hydroxy-4-[(2S,3R)-3-(hydroxymethyl)oxiranyl]-3-methoxy-2,2-dimethyl-1-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]butyl 2,2,2-trichloroethyl carbonate | C17H25Cl3O10 | 详情 | 详情 | |
| (XIII) | 43442 | (4S)-4-[[(2R,4S,5R,6R)-6-((1R)-2-[[tert-butyl(diphenyl)silyl]oxy]-1-hydroxyethyl)-5-hydroxy-4-methoxy-3,3-dimethyltetrahydro-2H-pyran-2-yl]methyl]-1,3-dioxolan-2-one | C30H42O8Si | 详情 | 详情 | |
| (XIV) | 43443 | (4S,4aR,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxine-4-carboxylic acid | C15H22O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The compound was originally isolated from the fungal source N. gypsea var. incurvata. The synthesis of this compound was further described. Treatment of N-phthaloyltryptophan methyl ester (I) with tert-butyl hypochlorite and triethylamine at -78 C led to the formation of the intermediate 3-chloroindolenine (II), which was reacted with B-prenyl-9-BBN (III) to yield the 3-(1,1-dimethylpropenyl)indole (IV). Removal of the phthalimide protecting group of (IV) by hydrazinolysis provided aminoester (V). Protection of (V) as the tert-butyl carbamate, followed by ester hydrolysis with LiOH afforded the N-Boc-amino acid (VI). Coupling of protected amino acid (VI) with aminoester (V) by means of BOP-Cl gave dipeptide (VII). After removal of the Boc protecting group of (VII) with trifluoroacetic acid, ammonia-catalyzed cyclization provided diketopiperazine (VIII). Alternatively, diketopiperazine (VIII) was obtained by thermal cyclization of two molecules of aminoester (V) at 140 C. Oxidative cyclization by means of dimethyldioxirane (IX) produced a 1:1:2 mixture of syn:syn, anti:anti, and syn:anti diastereoisomeric heptacyclic compounds. Finally, the target syn:anti isomer was isolated by chromatography.
| 【1】 Schkeryantz, J.M.; et al.; Total synthesis of gypsetin, deoxybrevianamide E, brevianamide E, and tryprostatin B: Novel constructions of 2,3-disubstituted indoles. J Am Chem Soc 1999, 121, 51, 11964. |
| 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) | 31493 | methyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoate | C20H16N2O4 | 详情 | 详情 | |
| (II) | 31494 | methyl (2S)-3-(3-chloro-3H-indol-3-yl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate | C20H15ClN2O4 | 详情 | 详情 | |
| (III) | 31495 | 9-(3-methyl-2-butenyl)-9-borabicyclo[3.3.1]nonane | C13H23B | 详情 | 详情 | |
| (IV) | 31496 | methyl (2S)-3-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate | C25H24N2O4 | 详情 | 详情 | |
| (V) | 31497 | methyl (2S)-2-amino-3-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]propanoate | C17H22N2O2 | 详情 | 详情 | |
| (VI) | 31498 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]propionic acid | C21H28N2O4 | 详情 | 详情 | |
| (VII) | 31499 | methyl (2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]propanoyl]amino)-3-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]propanoate | C38H48N4O5 | 详情 | 详情 | |
| (VIII) | 31500 | (3S,6S)-3,6-bis[[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]methyl]-2,5-piperazinedione | C32H36N4O2 | 详情 | 详情 | |
| (IX) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXXIX)Assembly of the target compound: The condensation of intermediates (XXI) and (XXXIV) by means of 9-BBN, a PdCl2 catalyst and K3PO4 in hot DMF/water gives the adduct (XXXV), which is hydrolyzed with NaOH in methanol/water to yield the hydroxyacid (XXXVI). The macrolactonization of (XXXVI) by the Yamaguchi procedure using 2,4,6-trichlorobenzoyl chloride, TEA and DMAP in THF affords the macrolactone (XXXVII), which is desilylated with HF and pyridine in THF, furnishing the dihydroxylactone (XXXVIII). Finally, this compound is epoxidated by means of dimethyldioxirane (XXXIX) in dichloromethane.
| 【1】 Sawada, D.; et al.; Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis. J Am Chem Soc 2000, 122, 43, 10521. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 44519 | phenyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-10-undecenoate | C33H58O5Si2 | 详情 | 详情 | |
| (XXXIV) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 | |
| (XXXV) | 44528 | phenyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | C46H75NO7SSi2 | 详情 | 详情 | |
| (XXXVI) | 44473 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-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 | |
| (XXXVII) | 44446 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C38H67NO5SSi2 | 详情 | 详情 | |
| (XXXVIII) | 44447 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C26H39NO5S | 详情 | 详情 | |
| (XXXIX) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XXXVIII)Assembly of the target compound: The condensation of intermediates (XXI) and (XXXIII) by means of 9-BBN, a PdCl2 catalyst and K3PO4 in hot DMF/water gives the adduct (XXXIV), which is hydrolyzed with NaOH in methanol/water to yield the hydroxyacid (XXXV). The macrolactonization of (XXXV) by the Yamaguchi procedure using 2,4,6-trichlorobenzoyl chloride, TEA and DMAP in THF affords the macrolactone (XXXVI), which is desilylated with HF and pyridine in THF, furnishing the dihydroxylactone (XXXVII). Finally, this compound is epoxidated by means of dimethyldioxirane (XXXVIII) in dichloromethane to give the target epothilone B.
| 【1】 Sawada, D.; et al.; Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis. J Am Chem Soc 2000, 122, 43, 10521. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 44519 | phenyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-10-undecenoate | C33H58O5Si2 | 详情 | 详情 | |
| (XXXIII) | 46125 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate | C14H18INO2S | 详情 | 详情 | |
| (XXXIV) | 46126 | phenyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-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-12,16-heptadecadienoate | C47H77NO7SSi2 | 详情 | 详情 | |
| (XXXV) | 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 | |
| (XXXVI) | 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 | |
| (XXXVII) | 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 | |
| (XXXVIII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XII)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.
| 【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 | CAS号 | 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：(XXXII)The macrolactonization of (XXVIII) by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF provides the protected macrolactone (XXIX), which is deprotected with TFA in dichloromethane to give the trienic macrolactone (XXX). Selective hydrogenation of the disubstituted double bond of (XXX) by means of potassium azodicarboxylate (DKAD) and AcOH in dichloromethane yields the precursor (XXXI), which is finally epoxidized with dimethyldioxirane (XXXII) in dichloromethane to afford the target epothilone B.
| 【1】 White, J.D.; Carter, R.G.; Sundermann, K.F.; Wartmann, M.; Total synthesis of epothilone B, epothilone D, and cis- and trans-9,10-dehydroepothilone D. J Am Chem Soc 2001, 123, 23, 5407. |
| 【2】 White, J.D.; et al.; A highly stereoselective synthesis of epothilone B. J Org Chem 1999, 64, 3, 684. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVIII) | 46158 | (3S,6R,7S,8S,9Z,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-9,12,16-heptadecatrienoic acid | C39H69NO6SSi2 | 详情 | 详情 | |
| (XXIX) | 46159 | (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-10,13-cyclohexadecadiene-2,6-dione | C39H67NO5SSi2 | 详情 | 详情 | |
| (XXX) | 46160 | (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-10,13-cyclohexadecadiene-2,6-dione | C27H39NO5S | 详情 | 详情 | |
| (XXXI) | 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 | |
| (XXXII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(XII)The reaction of chiral aldehyde (I) with dimethyl diazomethylphosphonate (II) by means of tBu-OK in THF gives the acetylenic ester (III), which is condensed with ally bromide derivative (IV) by means of CuI and TEA in DMF/ethyl ether to yield the dienyne (V). The partial hydrogenation of (V) over a Lindlar catalyst in hexane affords the trienoic ester (VI). The hydrolysis of (VI) with NaOH in warm isopropanol provides the corresponding carboxylic acid (VII), which is selectively desilylated with TBAF in THF to give the hydroxyacid (VIII). The macrolactonization of (VIII) by means of 2,4,6-trichlorobenzoyl chloride and TEA in benzene/THF yields the protected macrolactone (IX), which is deprotected with TFA in dichloromethane to afford the trienic macrolactone (X). Selective hydrogenation of the disubstituted double bond of (X) by means of potassium azodicarboxylate (DKAD) and HOAc in dichloromethane provides the precursor (XI), which is finally epoxidated with dimethyldioxirane (XII) in dichloromethane to furnish the target epothilone B.
| 【1】 White, J.D.; et al.; Improved synthesis of epothilone B employing alkylation of an alkyne for assembly of subunits. Org Lett 1999, 1, 9, 1431. |
| 【2】 White, J.D.; et al.; A highly stereoselective synthesis of epothilone B. J Org Chem 1999, 64, 3, 684. |
| 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) | 46155 | methyl (3S,6R,7S,8R)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5,9-dioxononanoate | C26H52O6Si2 | 详情 | 详情 | |
| (II) | 42709 | Diazomethylphoshonic acid dimethyl ester | 27491-70-9 | C3H7N2O3P | 详情 | 详情 |
| (III) | 46161 | methyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-9-decynoate | C27H52O5Si2 | 详情 | 详情 | |
| (IV) | 46147 | 4-((1E,3S,5Z)-7-bromo-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-1,5-heptadienyl)-2-methyl-1,3-thiazole; (1S,3Z)-5-bromo-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl tert-butyl(dimethyl)silyl ether | C19H32BrNOSSi | 详情 | 详情 | |
| (V) | 46162 | methyl (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-heptadecadien-9-ynoate | C46H83NO6SSi3 | 详情 | 详情 | |
| (VI) | 46156 | methyl (3S,6R,7S,8S,9Z,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-9,12,16-heptadecatrienoate | C46H85NO6SSi3 | 详情 | 详情 | |
| (VII) | 46157 | (3S,6R,7S,8S,9Z,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-9,12,16-heptadecatrienoic acid | C45H83NO6SSi3 | 详情 | 详情 | |
| (VIII) | 46158 | (3S,6R,7S,8S,9Z,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-9,12,16-heptadecatrienoic acid | C39H69NO6SSi2 | 详情 | 详情 | |
| (IX) | 46159 | (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-10,13-cyclohexadecadiene-2,6-dione | C39H67NO5SSi2 | 详情 | 详情 | |
| (X) | 46160 | (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-10,13-cyclohexadecadiene-2,6-dione | C27H39NO5S | 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 |