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【结 构 式】 
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【分子编号】42440 【品名】(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-carbaldehyde 【CA登记号】 |
【 分 子 式 】C41H59ClO7Si 【 分 子 量 】727.45346 【元素组成】C 67.7% H 8.17% Cl 4.87% O 15.4% Si 3.86% |
合成路线1
该中间体在本合成路线中的序号：(LXXX)Synthesis of intermediate (LXXI): The reaction of aldehyde (LXIV) with (S,S)-diisopropyl-(E)-crotyl boronate (DISCB) in toluene gives the alcohol (LXV), which is protected with Bn-Br and NaH yielding the benzyl ether (LXVI). The oxidation of the terminal double bond of (LXVI) with OsO4 and NaIO4 affords the aldehyde (LXVII), which is treated with (DISAB) to provide the allyl alcohol (LVIII). The silylation of (LXVIII) with Tips-OTf, followed by debenzylation with Li/NH3, gives the expected disilylated triol (LXIX). The oxidation of the terminal double bond of (LXIX) with OsO4 and NaIO4, with simultaneous cyclization yields the dihydropyran derivative (LXX), which is epoxidated with dimethyldioxirane (DMDO) in dichloromethane/acetone to afford the desired epoxide intermediate (LXXI).
| 【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LV) | 42415 | tributyl(2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-propenyl)stannane | C21H42O2Sn | 详情 | 详情 | |
| (LXIV) | 42425 | 2-[(triisopropylsilyl)oxy]acetaldehyde | C11H24O2Si | 详情 | 详情 | |
| (LXV) | 42426 | (2R,3R)-3-methyl-1-[(triisopropylsilyl)oxy]-4-penten-2-ol | C15H32O2Si | 详情 | 详情 | |
| (LXVI) | 42427 | benzyl (1R,2R)-2-methyl-1-[[(triisopropylsilyl)oxy]methyl]-3-butenyl ether; [[(2R,3R)-2-(benzyloxy)-3-methyl-4-pentenyl]oxy](triisopropyl)silane | C22H38O2Si | 详情 | 详情 | |
| (LXVII) | 42428 | (2S,3R)-3-(benzyloxy)-2-methyl-4-[(triisopropylsilyl)oxy]butanal | C21H36O3Si | 详情 | 详情 | |
| (LXVIII) | 42429 | (4S,5R,6R)-6-(benzyloxy)-5-methyl-7-[(triisopropylsilyl)oxy]-1-hepten-4-ol | C24H42O3Si | 详情 | 详情 | |
| (LXIX) | 42430 | (5S,6S,7R)-5-allyl-7-(benzyloxy)-3,3,10,10-tetraisopropyl-2,6,11-trimethyl-4,9-dioxa-3,10-disiladodecane; benzyl (1R,2S,3S)-2-methyl-3-[(triisopropylsilyl)oxy]-1-[[(triisopropylsilyl)oxy]methyl]-5-hexenyl ether | C33H62O3Si2 | 详情 | 详情 | |
| (LXX) | 42431 | triisopropyl([(2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]methoxy)silane; [(2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]methyl triisopropylsilyl ether | C25H52O3Si2 | 详情 | 详情 | |
| (LXXI) | 42432 | triisopropyl([(1S,3R,4S,5R,6S)-4-methyl-5-[(triisopropylsilyl)oxy]-2,7-dioxabicyclo[4.1.0]hept-3-yl]methoxy)silane; [(1S,3R,4S,5R,6S)-4-methyl-5-[(triisopropylsilyl)oxy]-2,7-dioxabicyclo[4.1.0]hept-3-yl]methyl triisopropylsilyl ether | C25H52O4Si2 | 详情 | 详情 | |
| (LXXII) | 42433 | (2R,3R,4R,5S,6R)-2-(2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-propenyl)-5-methyl-4-[(triisopropylsilyl)oxy]-6-[[(triisopropylsilyl)oxy]methyl]tetrahydro-2H-pyran-3-ol | C34H68O6Si2 | 详情 | 详情 | |
| (LXXIII) | 42434 | (2R,3S,4R,5R,6R)-2-(2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-propenyl)-6-(hydroxymethyl)-5-methyltetrahydro-2H-pyran-3,4-diol | C16H28O6 | 详情 | 详情 | |
| (LXXIV) | 42435 | tert-butyl(dimethyl)silyl [(2R,3R,4R,5S,6R)-6-(2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-propenyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]methyl ether; tert-butyl([(2R,3R,4R,5S,6R)-6-(2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-propenyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]methoxy)dimethylsilane | C38H58O8Si | 详情 | 详情 | |
| (LXXV) | 42436 | (2S)-4-([(2R,3S,4R,5R,6R)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,4-bis[(4-methoxybenzyl)oxy]-5-methyltetrahydro-2H-pyran-2-yl]methyl)-2-hydroxy-4-pentenyl pivalate | C40H62O9Si | 详情 | 详情 | |
| (LXXVI) | 42437 | (2S)-4-([(2R,3S,4R,5R,6R)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,4-bis[(4-methoxybenzyl)oxy]-5-methyltetrahydro-2H-pyran-2-yl]methyl)-2-[(triisopropylsilyl)oxy]-4-penten-1-ol | C44H74O8Si2 | 详情 | 详情 | |
| (LXXVII) | 42438 | (2S)-4-([(2R,3S,4R,5R,6R)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,4-bis[(4-methoxybenzyl)oxy]-5-methyltetrahydro-2H-pyran-2-yl]methyl)-2-[(triisopropylsilyl)oxy]-4-pentenal | C44H72O8Si2 | 详情 | 详情 | |
| (LXXVIII) | 31608 | 2,3-dichloro-1-propene | 78-88-6 | C3H4Cl2 | 详情 | 详情 |
| (LXXIX) | 42439 | ([(1S,2E)-1-[2-([(2R,3S,4R,5R,6R)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,4-bis[(4-methoxybenzyl)oxy]-5-methyltetrahydro-2H-pyran-2-yl]methyl)-2-propenyl]-4-chloro-2,4-pentadienyl]oxy)(triisopropyl)silane; tert-butyl(dimethyl)silyl [(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]methyl ether | C47H75ClO7Si2 | 详情 | 详情 | |
| (LXXX) | 42440 | (2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-carbaldehyde | C41H59ClO7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXXX)Synthesis of intermediate (LXXXV): The condensation of aldehyde intermediate (LXXX) with iododihydropyran (LXIII) by means of n-BuLi in ethyl ether gives the adduct (LXXXI), which is methoxylated with NIS, HC(OMe)3, Bu3SnH and AIBN, yielding the intermediate (LXXXII). Desilylation of (LXXXII) with TBAF and resilylation with TBDMSCl and imidazole to afford silylated (LXXXIII) now switch the Tips groups of (LXXXII) to the more labile Tbdms groups. The selective desilylation of the primary Tbdms group of (LXXXIII) with HF in pyridine/methanol gives the butanol derivative (LXXXIV), which is treated successively with Ts2O, NaI and finally with PPh3 and DIEA in hot acetonitrile/methanol to yield the desired phosphonium iodide intermediate (LXXXV).
| 【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXIII) | 42424 | (4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether | C28H57IO3Si2 | 详情 | 详情 | |
| (LXXX) | 42440 | (2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-carbaldehyde | C41H59ClO7Si | 详情 | 详情 | |
| (LXXXI) | 42441 | (S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-d | C69H117ClO10Si3 | 详情 | 详情 | |
| (LXXXII) | 42442 | (S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,4S,5S,6R)-2-methoxy-5-methyl-4-[(triisopropylsilyl)oxy]-6-[4-[(triisopropylsilyl)oxy | C70H121ClO11Si3 | 详情 | 详情 | |
| (LXXXIII) | 42443 | (S)-[(2R,4S,5S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis | C61H103ClO11Si3 | 详情 | 详情 | |
| (LXXXIV) | 42444 | 4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methoxy | C55H89ClO11Si2 | 详情 | 详情 | |
| (LXXXV) | 42445 | (4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox | C73H103ClIO10PSi2 | 详情 | 详情 |