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【结 构 式】 
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【分子编号】41549 【品名】(E)-4-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2-methyl-2-butenal 【CA登记号】n/a |
【 分 子 式 】C27H46O4Si 【 分 子 量 】462.74534 【元素组成】C 70.08% H 10.02% O 13.83% Si 6.07% |
合成路线1
该中间体在本合成路线中的序号：(XV)The cyclization of tetrahydropyran (I) with 2-butylacrolein (II) by means of K2CO3 at 110 C gives the spirodipyran (III), which is epoxidated with dimethyldioxirane in dichloromethane yielding the epoxide (IV). The rearrangement of (IV) by means of camphorsulfonic acid (CSA) affording the carbaldehyde (V), which is condensed with lithium trimethylsilylacetylene (VI) affording carbinol (VII) with incorrect stereochemistry. The oxidation of (VII) with DMP in dichloromethane providing the ketone (VIII), which is reduced with L-Selectride to the carbinol (IX) with the correct stereochemistry. The treatment of (IX) with K2CO3 in MeOH eliminates the trimethylsilyl group giving the acetylene (X), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding (XI). The selective desilylation of (XI) with HF·pyr in THF affords the primary alcohol (XII), which is oxidated with DMP in dichloromethane affording the aldehyde (VIII). The Wittig condensation of (XIII) with phosphorane (XIV) in hot chlorobenzene furnishes the aldehyde (XV).
| 【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382. |
| 【2】 Cuzzupe, A.N.; et al.; Total synthesis of (-)-reveromycin B. Org Lett 2000, 2, 2, 191. |
| 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) | 41537 | tert-butyl(dimethyl)[2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethoxy]silane; tert-butyl(dimethyl)silyl 2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethyl ether | C15H30O2Si | 详情 | 详情 | |
| (II) | 41538 | (Z)-2-butyl-2-butenal | C8H14O | 详情 | 详情 | |
| (III) | 41539 | tert-butyl(dimethyl)silyl 2-[(2R,3S,6S)-9-butyl-3-methyl-1,7-dioxaspiro[5.5]undec-8-en-2-yl]ethyl ether; tert-butyl[2-[(2R,3S,6S)-9-butyl-3-methyl-1,7-dioxaspiro[5.5]undec-8-en-2-yl]ethoxy]dimethylsilane | C22H42O3Si | 详情 | 详情 | |
| (IV) | 41540 | C22H42O4Si | 详情 | 详情 | ||
| (V) | 41541 | (2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]decane-2-carbaldehyde | n/a | C22H42O4Si | 详情 | 详情 |
| (VI) | 16299 | Lithium (trimethylsilyl)acetylide; [2-(Trimethylsilyl)ethynyl]lithium | 54655-07-1 | C5H9LiSi | 详情 | 详情 |
| (VII) | 41542 | (1R)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-ol | n/a | C27H52O4Si2 | 详情 | 详情 |
| (VIII) | 41543 | 1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-one | n/a | C27H50O4Si2 | 详情 | 详情 |
| (IX) | 41544 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-3-(trimethylsilyl)-2-propyn-1-ol | n/a | C27H52O4Si2 | 详情 | 详情 |
| (X) | 41545 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propyn-1-ol | n/a | C24H44O4Si | 详情 | 详情 |
| (XI) | 41546 | (1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propynyl tert-butyl(dimethyl)silyl ether; tert-butyl([(1S)-1-[(2R,5S,7R,8S)-2-butyl-7-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-2-propynyl]oxy)dimethylsilane | n/a | C30H58O4Si2 | 详情 | 详情 |
| (XII) | 41547 | 2-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-1-ethanol | n/a | C24H44O4Si | 详情 | 详情 |
| (XIII) | 41548 | 2-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]acetaldehyde | n/a | C24H42O4Si | 详情 | 详情 |
| (XIV) | 39940 | 2-(triphenylphosphoranylidene)propanal | C21H19OP | 详情 | 详情 | |
| (XV) | 41549 | (E)-4-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2-methyl-2-butenal | n/a | C27H46O4Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)A new Wittig condensation of aldehyde (XV) with phosphorane (XVI) in refluxing benzene gives the diunsaturated ester (XVII), which is reduced with DIBAL to the corresponding alcohol, and oxidated with DMP yielding the aldehyde (XVIII). The condensation of (XVIII) with the chiral propionyloxazolidinethione (XIX) by means of Sn(OTf)2 and 1-ethylpiperidine in dichloromethane affords the adduct (XX), which is treated with NaBH4 in THF to eliminate the chiral auxiliary and afford diol (XXI). The metalation of (XXI) with Bu3SnH and a Pd catalyst gives the vinylstannane (XXII), which is desilylated with TBAF in THF yielding the trihydroxycompound (XXIII). The condensation of stannane (XXIII) with iodobutenoic ester (XXIV) by means of a Pd catalyst affords the diunsaturated ester (XXV), which is selectively disilylated with TBDMSCl and imidazole in hot DMF to provide the disilyl ether (XXVI).
| 【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382. |
| 【2】 Cuzzupe, A.N.; et al.; Total synthesis of (-)-reveromycin B. Org Lett 2000, 2, 2, 191. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 41549 | (E)-4-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2-methyl-2-butenal | n/a | C27H46O4Si | 详情 | 详情 |
| (XVI) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (XVII) | 41550 | methyl (2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienoate | n/a | C30H50O5Si | 详情 | 详情 |
| (XVIII) | 41551 | (2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienal | C29H48O4Si | 详情 | 详情 | |
| (XIX) | 41552 | 1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-1-propanone | C9H15NO2S | 详情 | 详情 | |
| (XX) | 41553 | (2R,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-3-hydroxy-1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-2,6-dimethyl-4,6-octadien-1-one | C38H63NO6SSi | 详情 | 详情 | |
| (XXI) | 41554 | (2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol | C32H56O5Si | 详情 | 详情 | |
| (XXII) | 41555 | (2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-[(1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-(tributylstannyl)-2-propenyl]-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol | n/a | C44H84O5SiSn | 详情 | 详情 |
| (XXIII) | 41556 | (2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-[(1S,2E)-1-hydroxy-3-(tributylstannyl)-2-propenyl]-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol | n/a | C38H70O5Sn | 详情 | 详情 |
| (XXIV) | 41557 | 2-(trimethylsilyl)ethyl (E)-3-iodo-2-butenoate | n/a | C9H17IO2Si | 详情 | 详情 |
| (XXV) | 41558 | 2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-2-butyl-7-[(2E,4E,6S,7S)-6,8-dihydroxy-3,7-dimethyl-2,4-octadienyl]-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate | n/a | C35H60O7Si | 详情 | 详情 |
| (XXVI) | 41559 | 2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-7-((2E,4E,6S,7S)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-2,4-octadienyl)-2-butyl-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate | n/a | C47H88O7Si3 | 详情 | 详情 |