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【结 构 式】 
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【分子编号】42472 【品名】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 【CA登记号】 |
【 分 子 式 】C32H48O9 【 分 子 量 】576.72772 【元素组成】C 66.64% H 8.39% O 24.97% |
合成路线1
该中间体在本合成路线中的序号：(XXV)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 |
合成路线2
该中间体在本合成路线中的序号：(XXV)The oxidation of (XXV) with DMP in dichloromethane gives the aldehyde (XXVII), which is condensed with phosphorane (XXVIII) in refluxing toluene to yield aldehyde (XXIX). The reduction of (XXIX) with Zn(BH4)2 in ethyl ether affords alcohol (XXX), which is condensed with 2-sulfanylbenzothiazole (XXXI) by means of Bu3P and TMAD in benzene providing the thioether (XXXII). The oxidation of (XXXII) with Mo7O24(NH4)6 and H2O2 in ethanol gives the sulfone (XXXIII), which is condensed with the aldehyde (XXXIV) by means of LHMDS in THF to yield intermediate (XXXV). The selective monodesilylation of (XXXV) with PPTS in chloroform/methanol, followed by oxidation with DMP, affords the aldehyde (XXXVI).
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XXVII) | 42474 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-9-methyl-8-(2-oxoethyl)-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C32H46O9 | 详情 | 详情 | |
| (XXVIII) | 39940 | 2-(triphenylphosphoranylidene)propanal | C21H19OP | 详情 | 详情 | |
| (XXIX) | 42475 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-9-methyl-8-[(E)-3-methyl-4-oxo-2-butenyl]-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C35H50O9 | 详情 | 详情 | |
| (XXX) | 42476 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-[(E)-4-hydroxy-3-methyl-2-butenyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C35H52O9 | 详情 | 详情 | |
| (XXXI) | 24677 | 1,3-benzothiazol-2-ylhydrosulfide | 149-30-4 | C7H5NS2 | 详情 | 详情 |
| (XXXII) | 42477 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-8-[(E)-4-(1,3-benzothiazol-2-ylsulfanyl)-3-methyl-2-butenyl]-3-butyl-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C42H55NO8S2 | 详情 | 详情 | |
| (XXXIII) | 42478 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-8-[(E)-4-(1,3-benzothiazol-2-ylsulfonyl)-3-methyl-2-butenyl]-3-butyl-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C42H55NO10S2 | 详情 | 详情 | |
| (XXXIV) | 42479 | (2R,3S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-[(triethylsilyl)oxy]butanal | C17H38O3Si2 | 详情 | 详情 | |
| (XXXV) | 42480 | 1-allyl 4-((2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-[(2E,4E,6S,7S)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-[(triethylsilyl)oxy]-2,4-octadienyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl) succinate | C52H88O10Si2 | 详情 | 详情 | |
| (XXXVI) | 42481 | 1-allyl 4-[(2S,3R,6S,8R,9S)-2-[(1E,3E)-5-(allyloxy)-3-methyl-5-oxo-1,3-pentadienyl]-3-butyl-8-((2E,4E,6S,7R)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-oxo-2,4-octadienyl)-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] succinate | C46H72O10Si | 详情 | 详情 |