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【结 构 式】 
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【分子编号】44514 【品名】2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal 【CA登记号】 |
【 分 子 式 】C16H28O3 【 分 子 量 】268.39652 【元素组成】C 71.6% H 10.52% O 17.88% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Synthesis of undecenoic ester intermediate (XXI): The reaction of 2,2-dimethylpropane-1,3-diol (I) with benzaldehyde, TsOH and DIBAL gives the monobenzyl ether (II), which is oxidized with SO3/pyridine in dichloromethane, yielding the propionaldehyde (III). The condensation of (III) with butanone (IV) by means of LDA and TFAA affords the heptenone (V), which is epoxidated with H2O2 and NaOH in aq. methanol to provide the racemic epoxide (rac)-(VI). The reaction of ketone (VI) with O-methylhydroxylamine and NaOAc in methanol gives the corresponding oxime (rac)-(VII), which is treated with CuCN and Me-Li in ethyl ether to yield the beta-hydroxy oxime (rac)-(VIII). The treatment of (VIII) with H2 and Raney-Ni in acetone/THF affords the corresponding beta-hydroxy ketone (rac)-(IX), which is allylated with allyl bromide (X) and LHMDS in the presence of 1,3-dimethylperhydropyrimidin-2-one to give the beta-hydroxynonen-5-one (rac)-(XI). The reduction of (XI) with Me4NBH(OAc)3 and HOAc in acetonitrile yields the diol (rac)-(XII), which is protected with 2-methoxypropene (XIII) and TsOH, affording the 1,3-dioxane (rac)-(XIV). The reaction of (XIV) with Li in liquid ammonia, tert-butanol and THF provides the debenzylated primary alcohol (rac)-(XV), which is oxidized with tetrapropylammonium perrhuthenate in dichloromethane, giving the corresponding aldehyde (rac)-(XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (II) | 44529 | 3-(benzyloxy)-2,2-dimethyl-1-propanol | C12H18O2 | 详情 | 详情 | |
| (III) | 44504 | 3-(benzyloxy)-2,2-dimethylpropanal | C12H16O2 | 详情 | 详情 | |
| (IV) | 33891 | Methyl ethyl ketone; 2-Butanone | 78-93-3 | C4H8O | 详情 | 详情 |
| (V) | 44505 | (E)-7-(benzyloxy)-6,6-dimethyl-4-hepten-3-one | C16H22O2 | 详情 | 详情 | |
| (VI) | 44506 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone | C16H22O3 | 详情 | 详情 | |
| (VII) | 44507 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone O-methyloxime | C17H25NO3 | 详情 | 详情 | |
| (VIII) | 44508 | (4R,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone O-methyloxime | C18H29NO3 | 详情 | 详情 | |
| (IX) | 44509 | (4S,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone | C17H26O3 | 详情 | 详情 | |
| (X) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XI) | 44510 | (4S,6S,7R)-9-(benzyloxy)-7-hydroxy-4,6,8,8-tetramethyl-1-nonen-5-one | C20H30O3 | 详情 | 详情 | |
| (XII) | 44511 | (3R,4R,5S,6S)-1-(benzyloxy)-2,2,4,6-tetramethyl-8-nonene-3,5-diol | C20H32O3 | 详情 | 详情 | |
| (XIII) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (XIV) | 44512 | benzyl 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propyl ether; (4R,5S,6S)-4-[2-(benzyloxy)-1,1-dimethylethyl]-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxane | C23H36O3 | 详情 | 详情 | |
| (XV) | 44513 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-propanol | C16H30O3 | 详情 | 详情 | |
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)The asymmetric catalytic aldol reaction of aldehyde (XVI) with acetophenone by means of a chiral lanthane catalyst yields a diastereomeric mixture of hydroxyketones from which the desired isomer (XVII) is isolated. The Baeyer-Villiger oxidation of (XVII) with trimethylsilyl peroxide and SnCl4 affords the phenyl ester (XVIII), which is deprotected with BCl3 in dichloromethane, giving the trihydroxyester (XIX). The selective protection of (XIX) with Tbdms-OTf and DIEA in dichloromethane yields the bis silylated compound (XX), which is finally oxidized with DMP in dichloromethane to furnish the target undecenoic ester intermediate (XXI).
| 【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 |
|---|---|---|---|---|---|---|
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 | |
| (XVII) | 44515 | (3S)-3-hydroxy-4-methyl-1-phenyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-pentanone | C24H36O4 | 详情 | 详情 | |
| (XVIII) | 44516 | phenyl (3S)-3-hydroxy-4-methyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]pentanoate | C24H36O5 | 详情 | 详情 | |
| (XIX) | 44517 | phenyl (3S,5R,6R,7S,8S)-3,5,7-trihydroxy-4,4,6,8-tetramethyl-10-undecenoate | C21H32O5 | 详情 | 详情 | |
| (XX) | 44518 | phenyl (3S,5R,6S,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8-tetramethyl-10-undecenoate | C33H60O5Si2 | 详情 | 详情 | |
| (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 |
合成路线3
该中间体在本合成路线中的序号：(XVI)The reaction of 2,2-dimethylpropane-1,3-diol (I) with benzaldehyde, Ts-OH and DIBAL gives the monobenzyl ether (II), which is oxidized with SO3/pyridine in dichloromethane, yielding the propionaldehyde (III). The condensation of (III) with butanone (IV) by means of LDA and TFAA affords the heptenone (V), which is epoxidated with H2O2 and NaOH in aq. methanol to provide the racemic epoxide (rac)-(VI). The reaction of ketone (VI) with O-methylhydroxylamine and NaOAc in methanol gives the corresponding oxime (rac)-(VII), which is treated with CuCN and MeLi in ethyl ether to yield the beta-hydroxy oxime (rac)-(VIII). The treatment of (VIII) with H2 and Raney-Ni in acetone/THF affords the corresponding beta-hydroxy ketone (rac)-(IX), which is allylated with allyl bromide (X) and LHMDS in the presence of 1,3-dimethylperhydropyrimidin-2-one to give the beta-hydroxynonen-5-one (rac)-(XI). The reduction of (XI) with Me4NBH(OAc)3 and HOAc in acetonitrile yields the diol (rac)-(XII), which is protected with 2-methoxypropene (XIII) and Ts-OH, affording the 1,3-dioxane (rac)-(XIV). The reaction of (XIV) with Li in liquid ammonia, tert-butanol and THF provides the debenzylated primary alcohol (rac)-(XV), which is oxidized with tetrapropylammonium perrhuthenate in dichloromethane, giving the corresponding aldehyde (rac)-(XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (II) | 44529 | 3-(benzyloxy)-2,2-dimethyl-1-propanol | C12H18O2 | 详情 | 详情 | |
| (III) | 44504 | 3-(benzyloxy)-2,2-dimethylpropanal | C12H16O2 | 详情 | 详情 | |
| (IV) | 33891 | Methyl ethyl ketone; 2-Butanone | 78-93-3 | C4H8O | 详情 | 详情 |
| (V) | 44505 | (E)-7-(benzyloxy)-6,6-dimethyl-4-hepten-3-one | C16H22O2 | 详情 | 详情 | |
| (VI) | 44506 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone | C16H22O3 | 详情 | 详情 | |
| (VII) | 44507 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone O-methyloxime | C17H25NO3 | 详情 | 详情 | |
| (VIII) | 44508 | (4R,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone O-methyloxime | C18H29NO3 | 详情 | 详情 | |
| (IX) | 44509 | (4S,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone | C17H26O3 | 详情 | 详情 | |
| (X) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XI) | 44510 | (4S,6S,7R)-9-(benzyloxy)-7-hydroxy-4,6,8,8-tetramethyl-1-nonen-5-one | C20H30O3 | 详情 | 详情 | |
| (XII) | 44511 | (3R,4R,5S,6S)-1-(benzyloxy)-2,2,4,6-tetramethyl-8-nonene-3,5-diol | C20H32O3 | 详情 | 详情 | |
| (XIII) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (XIV) | 44512 | benzyl 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propyl ether; (4R,5S,6S)-4-[2-(benzyloxy)-1,1-dimethylethyl]-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxane | C23H36O3 | 详情 | 详情 | |
| (XV) | 44513 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-propanol | C16H30O3 | 详情 | 详情 | |
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XVI)The asymmetric catalytic aldol reaction of aldehyde (XVI) with acetophenone by means of a chiral lanthane catalyst yields a diastereomeric mixture of hydroxyketones from which the desired isomer (XVII) is isolated. The Baeyer-Villiger oxidation of (XVII) with trimethylsilyl peroxide and SnCl4 affords the phenyl ester (XVIII), which is deprotected with BCl3 in dichloromethane, giving the trihydroxyester (XIX). The selective protection of (XIX) with Tbdms-OTf and DIEA in dichloromethane yields the bis-silylated compound (XX), which is finally oxidized with DMP in dichloromethane to furnish the target undecenoic ester intermediate (XXI)
| 【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 |
|---|---|---|---|---|---|---|
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 | |
| (XVII) | 44515 | (3S)-3-hydroxy-4-methyl-1-phenyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-pentanone | C24H36O4 | 详情 | 详情 | |
| (XVIII) | 44516 | phenyl (3S)-3-hydroxy-4-methyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]pentanoate | C24H36O5 | 详情 | 详情 | |
| (XIX) | 44517 | phenyl (3S,5R,6R,7S,8S)-3,5,7-trihydroxy-4,4,6,8-tetramethyl-10-undecenoate | C21H32O5 | 详情 | 详情 | |
| (XX) | 44518 | phenyl (3S,5R,6S,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8-tetramethyl-10-undecenoate | C33H60O5Si2 | 详情 | 详情 | |
| (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 |
合成路线5
该中间体在本合成路线中的序号：(XVI)The reaction of 2,2-dimethylpropane-1,3-diol (I) with benzaldehyde, Ts-OH and DIBAL gives the monobenzyl ether (II), which is oxidized with SO3/pyridine in dichloromethane, yielding the propionaldehyde (III). The condensation of (III) with butanone (IV) by means of LDA and TFAA affords the heptenone (V), which is epoxidated with H2O2 and NaOH in aq. methanol to provide the racemic epoxide (rac)-(VI). The reaction of ketone (VI) with O-methylhydroxylamine and NaOAc in methanol gives the corresponding oxime (rac)-(VII), which is treated with CuCN and MeLi in ethyl ether to yield the beta-hydroxy oxime (rac)-(VIII). The treatment of (VIII) with H2 and Raney-Ni in acetone/THF affords the corresponding beta-hydroxy ketone (rac)-(IX), which is allylated with allyl bromide (X) and LHMDS in the presence of 1,3-dimethylperhydropyrimidin-2-one to give the beta-hydroxynonen-5-one (rac)-(XI). The reduction of (XI) with Me4NBH(OAc)3 and HOAc in acetonitrile yields the diol (rac)-(XII), which is protected with 2-methoxypropene (XIII) and Ts-OH, affording the 1,3-dioxane (rac)-(XIV). The reaction of (XIV) with Li in liquid ammonia, tert-butanol and THF provides the debenzylated primary alcohol (rac)-(XV), which is oxidized with tetrapropylammonium perrhuthenate in dichloromethane, giving the corresponding aldehyde (rac)-(XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (II) | 44529 | 3-(benzyloxy)-2,2-dimethyl-1-propanol | C12H18O2 | 详情 | 详情 | |
| (III) | 44504 | 3-(benzyloxy)-2,2-dimethylpropanal | C12H16O2 | 详情 | 详情 | |
| (IV) | 33891 | Methyl ethyl ketone; 2-Butanone | 78-93-3 | C4H8O | 详情 | 详情 |
| (V) | 44505 | (E)-7-(benzyloxy)-6,6-dimethyl-4-hepten-3-one | C16H22O2 | 详情 | 详情 | |
| (VI) | 44506 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone | C16H22O3 | 详情 | 详情 | |
| (VII) | 44507 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone O-methyloxime | C17H25NO3 | 详情 | 详情 | |
| (VIII) | 44508 | (4R,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone O-methyloxime | C18H29NO3 | 详情 | 详情 | |
| (IX) | 44509 | (4S,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone | C17H26O3 | 详情 | 详情 | |
| (X) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XI) | 44510 | (4S,6S,7R)-9-(benzyloxy)-7-hydroxy-4,6,8,8-tetramethyl-1-nonen-5-one | C20H30O3 | 详情 | 详情 | |
| (XII) | 44511 | (3R,4R,5S,6S)-1-(benzyloxy)-2,2,4,6-tetramethyl-8-nonene-3,5-diol | C20H32O3 | 详情 | 详情 | |
| (XIII) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (XIV) | 44512 | benzyl 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propyl ether; (4R,5S,6S)-4-[2-(benzyloxy)-1,1-dimethylethyl]-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxane | C23H36O3 | 详情 | 详情 | |
| (XV) | 44513 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-propanol | C16H30O3 | 详情 | 详情 | |
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 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 asymmetric catalytic aldol reaction of aldehyde (XVI) with acetophenone by means of a chiral lanthane catalyst yields a diastereomeric mixture of hydroxyketones from which the desired isomer (XVII) is isolated. The Baeyer-Villiger oxidation of (XVII) with trimethylsilyl peroxide and SnCl4 affords the phenyl ester (XVIII), which is deprotected with BCl3 in dichloromethane, giving the trihydroxyester (XIX). The selective protection of (XIX) with Tbdms-OTf and DIEA in dichloromethane yields the bis-silylated compound (XX), which is finally oxidized with DMP in dichloromethane to furnish the target undecenoic ester intermediate (XXI).
| 【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 |
|---|---|---|---|---|---|---|
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 | |
| (XVII) | 44515 | (3S)-3-hydroxy-4-methyl-1-phenyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-pentanone | C24H36O4 | 详情 | 详情 | |
| (XVIII) | 44516 | phenyl (3S)-3-hydroxy-4-methyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]pentanoate | C24H36O5 | 详情 | 详情 | |
| (XIX) | 44517 | phenyl (3S,5R,6R,7S,8S)-3,5,7-trihydroxy-4,4,6,8-tetramethyl-10-undecenoate | C21H32O5 | 详情 | 详情 | |
| (XX) | 44518 | phenyl (3S,5R,6S,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8-tetramethyl-10-undecenoate | C33H60O5Si2 | 详情 | 详情 | |
| (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 |
合成路线7
该中间体在本合成路线中的序号：(XVI)Synthesis of undecenoic ester intermediate (XXI): The reaction of 2,2-dimethylpropane-1,3-diol (I) with benzaldehyde, Ts-OH and DIBAL gives the monobenzyl ether (II), which is oxidized with SO3/pyridine in dichloromethane, yielding the propionaldehyde (III). The condensation of (III) with butanone (IV) by means of LDA and TFAA affords the heptenone (V), which is epoxidated with H2O2 and NaOH in aq. methanol to provide the racemic epoxide (rac)-(VI). The reaction of ketone (VI) with O-methylhydroxylamine and NaOAc in methanol gives the corresponding oxime (rac)-(VII), which is treated with CuCN and Me-Li in ethyl ether to yield the beta-hydroxy oxime (rac)-(VIII). The treatment of (VIII) with H2 and RaNi in acetone/THF affords the corresponding beta-hydroxy ketone (rac)-(IX), which is allylated with allyl bromide (X) and LHMDS in the presence of 1,3-dimethylperhydropyrimidin-2-one to give the beta-hydroxynonen-5-one (rac)-(XI). The reduction of (XI) with Me4NBH(OAc)3 and HOAc in acetonitrile yields the diol (rac)-(XII), which is protected with 2-methoxypropene (XIII) and Ts-OH, affording the 1,3-dioxane (rac)-(XIV). The reaction of (XIV) with Li in liquid ammonia, tert-butanol and THF provides the debenzylated primary alcohol (rac)-(XV), which is oxidized with tetrapropylammonium perrhuthenate in dichloromethane, giving the corresponding aldehyde (rac)-(XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (II) | 44529 | 3-(benzyloxy)-2,2-dimethyl-1-propanol | C12H18O2 | 详情 | 详情 | |
| (III) | 44504 | 3-(benzyloxy)-2,2-dimethylpropanal | C12H16O2 | 详情 | 详情 | |
| (IV) | 33891 | Methyl ethyl ketone; 2-Butanone | 78-93-3 | C4H8O | 详情 | 详情 |
| (V) | 44505 | (E)-7-(benzyloxy)-6,6-dimethyl-4-hepten-3-one | C16H22O2 | 详情 | 详情 | |
| (VI) | 44506 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone | C16H22O3 | 详情 | 详情 | |
| (VII) | 44507 | 1-[3-[2-(benzyloxy)-1,1-dimethylethyl]-2-oxiranyl]-1-propanone O-methyloxime | C17H25NO3 | 详情 | 详情 | |
| (VIII) | 44508 | (4R,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone O-methyloxime | C18H29NO3 | 详情 | 详情 | |
| (IX) | 44509 | (4S,5R)-7-(benzyloxy)-5-hydroxy-4,6,6-trimethyl-3-heptanone | C17H26O3 | 详情 | 详情 | |
| (X) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XI) | 44510 | (4S,6S,7R)-9-(benzyloxy)-7-hydroxy-4,6,8,8-tetramethyl-1-nonen-5-one | C20H30O3 | 详情 | 详情 | |
| (XII) | 44511 | (3R,4R,5S,6S)-1-(benzyloxy)-2,2,4,6-tetramethyl-8-nonene-3,5-diol | C20H32O3 | 详情 | 详情 | |
| (XIII) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (XIV) | 44512 | benzyl 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propyl ether; (4R,5S,6S)-4-[2-(benzyloxy)-1,1-dimethylethyl]-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxane | C23H36O3 | 详情 | 详情 | |
| (XV) | 44513 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-propanol | C16H30O3 | 详情 | 详情 | |
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XVI)The asymmetric catalytic aldol reaction of aldehyde (XVI) with acetophenone by means of a chiral lanthane catalyst yields a diastereomeric mixture of hydroxyketones from which the desired isomer (XVII) is isolated. The Baeyer-Villiger oxidation of (XVII) with trimethylsilyl peroxide and SnCl4 affords the phenyl ester (XVIII), which is deprotected with BCl3 in dichloromethane, giving the trihydroxyester (XIX). The selective protection of (XIX) with Tbdms-OTf and DIEA in dichloromethane yields the bis-silylated compound (XX), which is finally oxidized with DMP in dichloromethane to furnish the target undecenoic ester intermediate (XXI).
| 【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 |
|---|---|---|---|---|---|---|
| (XVI) | 44514 | 2-methyl-2-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]propanal | C16H28O3 | 详情 | 详情 | |
| (XVII) | 44515 | (3S)-3-hydroxy-4-methyl-1-phenyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]-1-pentanone | C24H36O4 | 详情 | 详情 | |
| (XVIII) | 44516 | phenyl (3S)-3-hydroxy-4-methyl-4-[(4R,5S,6S)-2,2,5-trimethyl-6-[(1S)-1-methyl-3-butenyl]-1,3-dioxan-4-yl]pentanoate | C24H36O5 | 详情 | 详情 | |
| (XIX) | 44517 | phenyl (3S,5R,6R,7S,8S)-3,5,7-trihydroxy-4,4,6,8-tetramethyl-10-undecenoate | C21H32O5 | 详情 | 详情 | |
| (XX) | 44518 | phenyl (3S,5R,6S,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8-tetramethyl-10-undecenoate | C33H60O5Si2 | 详情 | 详情 | |
| (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 |