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【结 构 式】 
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【分子编号】40307 【品名】(4S)-3-acryloyl-4-benzyl-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C13H13NO3 【 分 子 量 】231.25116 【元素组成】C 67.52% H 5.67% N 6.06% O 20.76% |
合成路线1
该中间体在本合成路线中的序号：(III)The protection of the allyl alcohol (I) with dihydropyran and PPTS in dichloromethane gives the tetrahydropyranyl ether (II), which is condensed with the chiral oxazolidinone (III) by means of BuLi and CuCN in THF to yield the adduct (IV). The hydroxylation of (IV) with Davis' oxaziridine, NaHMDS and CSA affords the alcohol (V), which is silylated with Tbdms-OTf and lutidine to provide the silyl ether (VII). The hydrolysis of the oxazolidinone group of (VII) with Et-SH and Et-SK in THF gives the thioester (VIII), which is methylated with Me2CuLi in ethyl ether, yielding the methyl ketone (IX). The condensation of (IX) with phosphonate (X) by means of BuLi in THF affords the diene (XI), which is treated with MgBr2 in ethyl ether in order to eliminate the THP protecting group and obtain the primary alcohol (XII). The sulfonation of (XII) with Ms2O and TEA in dichloromethane gives the mesylate (XIII), which is treated with LiBr in acetone to yield the allyl bromide (XIV). Finally, (XIV) is condensed with methyltriphenylphosphonium bromide (XV) by means of BuLi in THF affording the desired intermediate phosphonium salt (XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 46138 | (Z)-3-iodo-2-methyl-2-propen-1-ol | C4H7IO | 详情 | 详情 | |
| (II) | 46139 | (Z)-3-iodo-2-methyl-2-propenyl tetrahydro-2H-pyran-2-yl ether; 2-[[(Z)-3-iodo-2-methyl-2-propenyl]oxy]tetrahydro-2H-pyran | C9H15IO2 | 详情 | 详情 | |
| (III) | 40307 | (4S)-3-acryloyl-4-benzyl-1,3-oxazolidin-2-one | C13H13NO3 | 详情 | 详情 | |
| (IV) | 46140 | (4S)-4-benzyl-3-[(Z)-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C22H29NO5 | 详情 | 详情 | |
| (V) | 31834 | 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine;2-(Phenylsulfonyl)-3-phenyloxaziridine;2-Benzenesulfonyl-3-phenyloxaziridine;3-Phenyl-2-phenylsulfonyloxaziridine;3-Phenyl-N-phenylsulfonyloxaziridine;N-(Phenylsulfonyl)phenyloxaziridine;N-Benzenesulfonyl-3-phenyloxaziridine | 63160-13-4 | C13H11NO3S | 详情 | 详情 |
| (VI) | 46141 | (4S)-4-benzyl-3-[(2S,4Z)-2-hydroxy-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C22H29NO6 | 详情 | 详情 | |
| (VII) | 46142 | (4S)-4-benzyl-3-[(2S,4Z)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C28H43NO6Si | 详情 | 详情 | |
| (VIII) | 46143 | S-ethyl (2S,4Z)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenethioate | C20H38O4SSi | 详情 | 详情 | |
| (IX) | 46144 | (3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-7-(tetrahydro-2H-pyran-2-yloxy)-5-hepten-2-one | C19H36O4Si | 详情 | 详情 | |
| (X) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (XI) | 46145 | 4-[(1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(tetrahydro-2H-pyran-2-yloxy)-1,5-heptadienyl]-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S,3Z)-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5-(tetrahydro-2H-pyran-2-yloxy)-3-pentenyl ether | C24H41NO3SSi | 详情 | 详情 | |
| (XII) | 40824 | (2Z,5S,6E)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadien-1-ol | C19H33NO2SSi | 详情 | 详情 | |
| (XIII) | 46146 | tert-butyl(dimethyl)silyl (1S,3Z)-4-methyl-5-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1,5-heptadienyl)-2-methyl-1,3-thiazole | C22H39NO2S2Si | 详情 | 详情 | |
| (XIV) | 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 | |
| (XV) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
| (XVI) | 46148 | [(3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl](triphenyl)phosphonium bromide | C38H49BrNOPSSi | 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 protection of the allyl alcohol (I) with dihydropyran and PPTS in dichloromethane gives the tetrahydropyranyl ether (II), which is condensed with the chiral oxazolidinone (III) by means of BuLi and CuCN in THF, yielding the adduct (IV). The hydroxylation of (IV) with Davis' oxaziridine, NaHMDS and CSA affords the alcohol (V), which is silylated with Tbdms-OTf and lutidine, providing the silyl ether (VII). The hydrolysis of the oxazolidinone group of (VII) with Et-SH and Et-SK in THF gives the thioester (VIII), which is methylated with Me2CuLi in ethyl ether, yielding the methyl ketone (IX). The condensation of (IX) with phosphonate (X) by means of BuLi in THF affords the diene (XI), which is treated with MgBr2 in ethyl ether in order to eliminate the THP protecting group and obtain the primary alcohol (XII). The sulfonation of (XII) with Ms2O and TEA in dichloromethane gives the mesylate (XIII), which is treated with LiBr in acetone to yield the allyl bromide (XIV). Finally, (XIV) is condensed with methyltriphenylphosphonium bromide (XV) by means of BuLi in THF affording the desired intermediate phosphonium salt (XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 46138 | (Z)-3-iodo-2-methyl-2-propen-1-ol | C4H7IO | 详情 | 详情 | |
| (II) | 46139 | (Z)-3-iodo-2-methyl-2-propenyl tetrahydro-2H-pyran-2-yl ether; 2-[[(Z)-3-iodo-2-methyl-2-propenyl]oxy]tetrahydro-2H-pyran | C9H15IO2 | 详情 | 详情 | |
| (III) | 40307 | (4S)-3-acryloyl-4-benzyl-1,3-oxazolidin-2-one | C13H13NO3 | 详情 | 详情 | |
| (IV) | 46140 | (4S)-4-benzyl-3-[(Z)-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C22H29NO5 | 详情 | 详情 | |
| (V) | 31834 | 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine;2-(Phenylsulfonyl)-3-phenyloxaziridine;2-Benzenesulfonyl-3-phenyloxaziridine;3-Phenyl-2-phenylsulfonyloxaziridine;3-Phenyl-N-phenylsulfonyloxaziridine;N-(Phenylsulfonyl)phenyloxaziridine;N-Benzenesulfonyl-3-phenyloxaziridine | 63160-13-4 | C13H11NO3S | 详情 | 详情 |
| (VI) | 46141 | (4S)-4-benzyl-3-[(2S,4Z)-2-hydroxy-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C22H29NO6 | 详情 | 详情 | |
| (VII) | 46142 | (4S)-4-benzyl-3-[(2S,4Z)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenoyl]-1,3-oxazolidin-2-one | C28H43NO6Si | 详情 | 详情 | |
| (VIII) | 46143 | S-ethyl (2S,4Z)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-6-(tetrahydro-2H-pyran-2-yloxy)-4-hexenethioate | C20H38O4SSi | 详情 | 详情 | |
| (IX) | 46144 | (3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-7-(tetrahydro-2H-pyran-2-yloxy)-5-hepten-2-one | C19H36O4Si | 详情 | 详情 | |
| (X) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (XI) | 46145 | 4-[(1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(tetrahydro-2H-pyran-2-yloxy)-1,5-heptadienyl]-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S,3Z)-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5-(tetrahydro-2H-pyran-2-yloxy)-3-pentenyl ether | C24H41NO3SSi | 详情 | 详情 | |
| (XII) | 40824 | (2Z,5S,6E)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadien-1-ol | C19H33NO2SSi | 详情 | 详情 | |
| (XIII) | 46146 | tert-butyl(dimethyl)silyl (1S,3Z)-4-methyl-5-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1,5-heptadienyl)-2-methyl-1,3-thiazole | C22H39NO2S2Si | 详情 | 详情 | |
| (XIV) | 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 | |
| (XV) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
| (XVI) | 46148 | [(3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl](triphenyl)phosphonium bromide | C38H49BrNOPSSi | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)The condensation of 4-(ethylsulfanyl)-2-butynoic acid methyl ester (I) with the vinyl copper derivative (III) by means of DBU in THF gives the addition product (IV), which is treated with methyl chloroformate and LHMDS in THF yielding the malonic ester (V): The condensation of (V) with the chiral oxazolidinone (VI) by means of Cs2CO3 in acetonitrile affords the addition compound (VII), which is further condensed with the aldehyde (VIII) by means of Bu2B-OTf and TEA in dichloromethane giving the adduct (IX). The cyclization of (IX) by means of ZnCl2 and pyridine in dichloromethane yields the bicyclic compound (X), which is treated with allyl thioglycolate (XI) and LHMDS in ether producing the opening of the thiazolidinone ring. The resulting thiocarboxylic ester (XII) is submitted to cyclization by means of DBU in THF furnishing the tricyclic compound (XIII), which is selectively dehydrated and decarboxylated with Pd(OAc)2/PPh3 and pyr/Ac2O giving the tricyclic thiophenone (XIV). The oxidation of (XIV) with TBDMS-Cl, DBU and AgNO3 in hot DMSO affords the tricyclic thiophenedione (XV).
| 【1】 Waizumi, N.; et al.; Total synthesis of (-)-CP-263,114 (phomoidride B). J Am Chem Soc 2000, 122, 32, 7825. |
| 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) | 40302 | methyl 4-(propylsulfanyl)-2-butynoate | C8H12O2S | 详情 | 详情 | |
| (II) | 40303 | methyl 4-(propylsulfanyl)-2,3-butadienoate | C8H12O2S | 详情 | 详情 | |
| (III) | 40304 | (1E,8E)-1,8-decadienylcopper | C10H17Cu | 详情 | 详情 | |
| (IV) | 40305 | methyl (4E,11E)-3-[(E)-(propylsulfanyl)methylidene]-4,11-tridecadienoate | C18H30O2S | 详情 | 详情 | |
| (V) | 40306 | dimethyl 2-[(2E,9E)-1-[(Z)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C20H32O4S | 详情 | 详情 | |
| (VI) | 40307 | (4S)-3-acryloyl-4-benzyl-1,3-oxazolidin-2-one | C13H13NO3 | 详情 | 详情 | |
| (VII) | 40308 | dimethyl 2-[3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2-[(2E,9E)-1-[(E)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C33H45NO7S | 详情 | 详情 | |
| (VIII) | 40309 | (E)-4-[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-butenal | C13H22O3 | 详情 | 详情 | |
| (IX) | 40310 | dimethyl 2-[(2S,4E)-2-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-6-[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]-3-oxo-4-hexenyl]-2-[(2E,9E)-1-[(E)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C46H65NO10S | 详情 | 详情 | |
| (X) | 40311 | dimethyl (4S,6R,7R,8R,10R)-4-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-7-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-8-[(E)-6-octenyl]-5-oxo-10-(propylsulfanyl)bicyclo[4.3.1]dec-1(9)-ene-2,2-dicarboxylate | C46H65NO10S | 详情 | 详情 | |
| (XI) | 40312 | allyl 2-sulfanylacetate | C5H8O2S | 详情 | 详情 | |
| (XII) | 40313 | dimethyl (4S,6R,7R,8R,10R)-4-([[2-(allyloxy)-2-oxoethyl]sulfanyl]carbonyl)-7-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-8-[(E)-6-octenyl]-5-oxo-10-(propylsulfanyl)bicyclo[4.3.1]dec-1(9)-ene-2,2-dicarboxylate | C41H62O10S2 | 详情 | 详情 | |
| (XIII) | 40314 | 3-allyl 8,8-dimethyl (1R,2R,3S,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-hydroxy-11-[(E)-6-octenyl]-5-oxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]tridec-9-ene-3,8,8-tricarboxylate | C41H62O10S2 | 详情 | 详情 | |
| (XIV) | 40315 | dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-5-oxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate | C37H56O7S2 | 详情 | 详情 | |
| (XV) | 40316 | dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate | C37H54O8S2 | 详情 | 详情 |