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【结 构 式】 
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【分子编号】42460 【品名】triethyl[((1R,2S)-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butynyl)oxy]silane; 4-methoxybenzyl (3R,4S)-4-methyl-3-[(triethylsilyl)oxy]-5-hexynyl ether 【CA登记号】 |
【 分 子 式 】C21H34O3Si 【 分 子 量 】362.58466 【元素组成】C 69.56% H 9.45% O 13.24% Si 7.75% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Synthesis of alkyne (XIII). The reaction of the protected aldehyde (VIII) with (-)-(E)-crotyldiisopinocampheylborane (CDICB) by means of BF3/Et2O in THF gives the chiral unsaturated alcohol (IX), which is silylated with Tes-Cl and imidazole, yielding the protected unsaturated diol (X). Oxidation of the double bond of (X) with OsO4 and Pb(OAc)4 in toluene affords the aldehyde (XI), which is treated with CBr4, PPh3 and Et3N in dichloromethane to provide the dibromovinyl compound (XII). Finally, (XII) is treated with BuLi in THF to give the target acetylenic intermediate (XIII).
| 【1】 Shimizu, T.; et al.; Total synthesis of reveromycin A. Org Lett 2000, 2, 14, 2153. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 42455 | 3-[(4-methoxybenzyl)oxy]propanal | C11H14O3 | 详情 | 详情 | |
| (IX) | 42456 | (3R,4S)-1-[(4-methoxybenzyl)oxy]-4-methyl-5-hexen-3-ol | C15H22O3 | 详情 | 详情 | |
| (X) | 42457 | triethyl[((1R,2S)-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butenyl)oxy]silane; 4-methoxybenzyl (3R,4S)-4-methyl-3-[(triethylsilyl)oxy]-5-hexenyl ether | C21H36O3Si | 详情 | 详情 | |
| (XI) | 42458 | (2R,3R)-5-[(4-methoxybenzyl)oxy]-2-methyl-3-[(triethylsilyl)oxy]pentanal | C20H34O4Si | 详情 | 详情 | |
| (XII) | 42459 | [((1R,2S)-4,4-dibromo-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butenyl)oxy](triethyl)silane; (1R,2S)-4,4-dibromo-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butenyl triethylsilyl ether | C21H34Br2O3Si | 详情 | 详情 | |
| (XIII) | 42460 | triethyl[((1R,2S)-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butynyl)oxy]silane; 4-methoxybenzyl (3R,4S)-4-methyl-3-[(triethylsilyl)oxy]-5-hexynyl ether | C21H34O3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)The condensation of intermediates (VII) and (XIII) by means of n-BuLi in THF, followed by hydrogenation, with H2 over Pd/C in ethyl acetate gives the protected ketone (XIV). The deprotection of the two Tes groups of (XIV) with CSA in chloroform/methanol gives rise to simultaneous intramolecular ketalization to give the two 6,6-spiroketals (XV) and (XVI) with opposite stereochemistry at the spiro center, which are separated by conventional methods. Spiroketal (XV), with correct stereochemistry, is treated with MeI and NaHCO3 in acetone/water to eliminate the mtm protecting group, and the resulting alcohol is esterified with monoallyl succinate (XVII) by means of DCC and DMAP in dichloromethane, yielding the ester (XVIII). The desilylation of (XVIII) with HF in pyridine/THF, followed by oxidation of the resulting alcohol with DMP, affords the aldehyde (XX), which is condensed with phosphonate (XXII) by means of LHMDS and HMPA in THF to give unsaturated allyl ester (XXIII). Elimination of the mpm protecting group of (XXIII) with DDQ in dichloromethane affords the primary alcohol (XXV). Spiroketal (XVI), with opposite stereochemistry, can be recovered by submitting it to the same sequence of reactions as (XV) to furnish intermediates (XIX), (XXI), (XXIV) and finally (XXVI), which is isomerized to (XXV) by treatment with CSA in chloroform/methanol.
| 【1】 Shimizu, T.; et al.; Total synthesis of reveromycin A. Org Lett 2000, 2, 14, 2153. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 42454 | C35H59NO5Si2 | 详情 | 详情 | ||
| (XIII) | 42460 | triethyl[((1R,2S)-1-[2-[(4-methoxybenzyl)oxy]ethyl]-2-methyl-3-butynyl)oxy]silane; 4-methoxybenzyl (3R,4S)-4-methyl-3-[(triethylsilyl)oxy]-5-hexynyl ether | C21H34O3Si | 详情 | 详情 | |
| (XIV) | 42461 | C54H90O7Si3 | 详情 | 详情 | ||
| (XV) | 42462 | C42H60O6Si | 详情 | 详情 | ||
| (XVI) | 42463 | C42H60O6Si | 详情 | 详情 | ||
| (XVII) | 42464 | 4-(allyloxy)-4-oxobutyric acid | C7H10O4 | 详情 | 详情 | |
| (XVIII) | 42465 | 1-allyl 4-((2S,3R,6S,8R,9S)-3-butyl-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C48H66O9Si | 详情 | 详情 | |
| (XIX) | 42466 | 1-allyl 4-((2S,3R,6R,8R,9S)-3-butyl-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C48H66O9Si | 详情 | 详情 | |
| (XX) | 42467 | 1-allyl 4-((2R,3R,6S,8R,9S)-3-butyl-2-formyl-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C32H46O9 | 详情 | 详情 | |
| (XXI) | 42468 | 1-allyl 4-((2R,3R,6R,8R,9S)-3-butyl-2-formyl-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C32H46O9 | 详情 | 详情 | |
| (XXII) | 42469 | allyl (E)-4-(diethoxyphosphoryl)-3-methyl-2-butenoate | C12H21O5P | 详情 | 详情 | |
| (XXIII) | 42470 | 1-allyl 4-((2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C40H56O10 | 详情 | 详情 | |
| (XXIV) | 42471 | 1-allyl 4-((2S,3R,6R,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-[2-[(4-methoxybenzyl)oxy]ethyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C40H56O10 | 详情 | 详情 | |
| (XXV) | 42472 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-(2-hydroxyethyl)-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C32H48O9 | 详情 | 详情 | |
| (XXVI) | 42473 | 1-allyl 4-[(2S,3R,6R,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-(2-hydroxyethyl)-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C32H48O9 | 详情 | 详情 |