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【结 构 式】 
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【分子编号】42386 【品名】(2R,3R)-2-[(1S)-2-iodo-1-methyl-2-propenyl]-3-methyl-1,5-dioxaspiro[5.5]undecane 【CA登记号】 |
【 分 子 式 】C14H23IO2 【 分 子 量 】350.23989 【元素组成】C 48.01% H 6.62% I 36.23% O 9.14% |
合成路线1
该中间体在本合成路线中的序号：(XX)Synthesis of intermediate (XX): The oxidation of silylated diol (XV) with OsO4, Pb(OAc)4 and N-methylmorpholine-N-oxide (NMO) in acetone/benzene gives the aldehyde (XVI), which is condensed with formaldehyde by means of KOtBu and B-iodo-9-borabicyclo[3.3.1]nonane (B-I-9-BBN) to yield the iodovinyl compound (XVII). The desilylation of (XVII) with HF and pyridine in THF affords the diol (XVIII), which is treated with 1,1-dimethoxycyclohexane (XIX) and pyridinium p-toluenesulfonate (PPTS) to provide the desired intermediate (XX).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 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) | 42381 | (5S,6R)-2,2,3,3,6,9,9,10,10-nonamethyl-5-[(1R)-1-methyl-2-propenyl]-4,8-dioxa-3,9-disilaundecane; tert-butyl(dimethyl)silyl (2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-hexenyl ether | C20H44O2Si2 | 详情 | 详情 | |
| (XVI) | 42382 | (3R,4S,5R)-4,6-bis[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethylhexanal | C20H44O3Si2 | 详情 | 详情 | |
| (XVII) | 42383 | tert-butyl(dimethyl)silyl (2R,3R,4S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-2,4-dimethyl-5-hexenyl ether; (5R,6R)-5-[(1S)-2-iodo-1-methyl-2-propenyl]-2,2,3,3,6,9,9,10,10-nonamethyl-4,8-dioxa-3,9-disilaundecane | C20H43IO2Si2 | 详情 | 详情 | |
| (XVIII) | 42384 | (2R,3R,4S)-5-iodo-2,4-dimethyl-5-hexene-1,3-diol | C8H15IO2 | 详情 | 详情 | |
| (XIX) | 42385 | 1,1-dimethoxycyclohexane; 1-methoxycyclohexyl methyl ether | 933-40-4 | C8H16O2 | 详情 | 详情 |
| (XX) | 42386 | (2R,3R)-2-[(1S)-2-iodo-1-methyl-2-propenyl]-3-methyl-1,5-dioxaspiro[5.5]undecane | C14H23IO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XX)Synthesis of intermediate (XLIII): The condensation of dithiane intermediate (VII) with epoxide intermediate (XIV) by means of NaOtBu and n-BuLi gives alcohol (XXXIV), which is converted into epoxide (XXXV) by treatment with pyridinium p-toluenesulfonate (PPTS), NaH and tosyl-imidazole in THF. The condensation of (XXXV) with intermediate iodovinyl compound (XX) by means of n-BuLi in THF yields the diol (XXXVI), which is treated with CaCO3 and NIS to afford the spiroketal (XXXVII). The monoacylation of (XXXVIII) with methoxyacetyl chloride (XXXVIII) and LiNH2, followed by cleavage of the cyclohexylidene ketal with PPTS, provides the triol (XXXIX), which is selectively silylated at the primary OH group with TBDMSCl to give the silyl ether (LX). The acylation of the two secondary OH groups of (LX) with Ac2O and DMAP yields the diacetate (XLI), which is desilylated with HF and pyridine in acetonitrile afford the primary alcohol (XLII). Finally, this compound is oxidized with DMP in dichloromethane to furnish the desired intermediate aldehyde (XLIII).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 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) | 42373 | benzyl (3S,5S)-3,5-bis[[tert-butyl(diphenyl)silyl]oxy]-6-(1,3-dithian-2-yl)hexyl ether; (5S,7S)-5-[2-(benzyloxy)ethyl]-7-(1,3-dithian-2-ylmethyl)-2,2,10,10-tetramethyl-3,3,9,9-tetraphenyl-4,8-dioxa-3,9-disilaundecane | C49H62O3S2Si2 | 详情 | 详情 | |
| (XIV) | 42380 | tert-butyl(dimethyl)silyl (1R)-2-(2-ethoxyethoxy)-1-[[(2S)-2-methyloxiranyl]methyl]ethyl ether; (5R)-2,2,3,3-tetramethyl-5-[[(2S)-2-methyloxiranyl]methyl]-4,7,10-trioxa-3-siladodecane | C16H34O4Si | 详情 | 详情 | |
| (XX) | 42386 | (2R,3R)-2-[(1S)-2-iodo-1-methyl-2-propenyl]-3-methyl-1,5-dioxaspiro[5.5]undecane | C14H23IO2 | 详情 | 详情 | |
| (XXXIV) | 42396 | (2S,4R)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-4-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-ethoxyethoxy)-2-methyl-2-pentanol | C65H96O7S2Si3 | 详情 | 详情 | |
| (XXXV) | 42397 | (2S)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-2-methyl-3-[(2R)oxiranyl]-2-propanol | C55H72O5S2Si2 | 详情 | 详情 | |
| (XXXVI) | 42398 | (2S,4S)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-2-methyl-6-[(1R)-1-[(2S,3R)-3-methyl-1,5-dioxaspiro[5.5]undec-2-yl]ethyl]-6-heptene-2,4-diol | C69H96O7S2Si2 | 详情 | 详情 | |
| (XXXVII) | 42399 | (2S,4S,6S,8S,10S)-8-[2-(benzyloxy)ethyl]-4-methyl-2-(2-[(1R)-1-[(2S,3R)-3-methyl-1,5-dioxaspiro[5.5]undec-2-yl]ethyl]-2-propenyl)-1,7-dioxaspiro[5.5]undecane-4,10-diol | C34H52O7 | 详情 | 详情 | |
| (XXXVIII) | 13429 | 2-Methoxyacetyl chloride; Methoxyacetyl chloride | 38870-89-2 | C3H5ClO2 | 详情 | 详情 |
| (XXXIX) | 42400 | 2-((2S,4S,6S,8S,10S)-8-[2-[(1R,2S,3R)-2,4-dihydroxy-1,3-dimethylbutyl]-2-propenyl]-4,10-dihydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate | C24H42O9 | 详情 | 详情 | |
| (XL) | 42401 | 2-[(2S,4S,8S,10S)-8-[2-((1R,2S,3R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-hydroxy-1,3-dimethylbutyl)-2-propenyl]-4,10-dihydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]ethyl 2-methoxyacetate | C30H56O9Si | 详情 | 详情 | |
| (XLI) | 42402 | 2-[(2S,4S,8S,10S)-4-(acetoxy)-8-[2-((1R,2S,3R)-2-(acetoxy)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,3-dimethylbutyl)-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]ethyl 2-methoxyacetate | C34H60O11Si | 详情 | 详情 | |
| (XLII) | 42403 | 2-((2S,4S,6S,8S,10S)-4-(acetoxy)-8-[2-[(1R,2S,3R)-2-(acetoxy)-4-hydroxy-1,3-dimethylbutyl]-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate | C28H46O11 | 详情 | 详情 | |
| (XLIII) | 42404 | 2-((2S,4S,6S,8S,10S)-4-(acetoxy)-8-[2-[(1R,2S,3S)-2-(acetoxy)-1,3-dimethyl-4-oxobutyl]-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate | C28H44O11 | 详情 | 详情 |