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【结 构 式】 
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【分子编号】42395 【品名】tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane 【CA登记号】 |
【 分 子 式 】C28H47IO7Si 【 分 子 量 】650.66695 【元素组成】C 51.69% H 7.28% I 19.5% O 17.21% Si 4.32% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Synthesis of intermediate (XXXIII): The silylation of epoxide (XXI) with TBDMSCl gives the silyl ether (XXII), which is condensed with 1,3-dithiane (VI) by means of n-BuLi to yield the alcohol (XXIII). Epoxidation of (XXIII) with TBAF and NaH affords the epoxide (XXIV), which is condensed with vinyl lithium and CuCN to provide the allyl alcohol (XXV). The methylation of (XXV) with MeI and NaH in THF gives the methyl ether (XXVI). The silylation of epoxide (XXI) with TBDPSCl gives the silyl ether (XXVII), which is condensed with vinyl lithium (II) by means of CuCN in THF, yielding the allyl alcohol (XXVIII). The reaction of (XXVIII) with Boc-ON, n-BuLi and IBr affords the cyclic carbonate (XXIX), which is treated with K2CO3 in MeOH and silylated with TBDPSCl to provide the protected epoxide (XXX). The condensation of epoxide (XXX) with allyl ether (XXVI) by means of NaOtBu and n-BuLi in THF furnished the adduct (XXXI), which is cyclized by means of TBAF and converted into the acetylenic tetrahydropyran (XXXII). Finally, the iodination and reprotection of (XXXII) with Bu3SnH, AIBN, NIS, Mpm-OCH2Cl and DIEA gives the desired intermediate (XXXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (II) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VI) | 42372 | 1,3-dithiane | 505-23-7 | C4H8S2 | 详情 | 详情 |
| (XXI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XXII) | 42374 | tert-butyl(dimethyl)[(2R)oxiranylmethoxy]silane; tert-butyl(dimethyl)silyl (2R)oxiranylmethyl ether | C9H20O2Si | 详情 | 详情 | |
| (XXIII) | 42387 | (2R)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-(1,3-dithian-2-yl)-2-propanol | C13H28O2S2Si | 详情 | 详情 | |
| (XXIV) | 42388 | (2R)-2-(1,3-dithian-2-ylmethyl)oxirane | C7H12OS2 | 详情 | 详情 | |
| (XXV) | 42389 | (2S)-1-(1,3-dithian-2-yl)-4-penten-2-ol | C9H16OS2 | 详情 | 详情 | |
| (XXVI) | 42390 | (1S)-1-(1,3-dithian-2-ylmethyl)-3-butenyl methyl ether; 2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithiane | C10H18OS2 | 详情 | 详情 | |
| (XXVII) | 26421 | tert-butyl[(2R)oxiranylmethoxy]diphenylsilane; tert-butyl(diphenyl)silyl (2R)oxiranylmethyl ether | C19H24O2Si | 详情 | 详情 | |
| (XXVIII) | 26422 | (2R)-1-[[tert-butyl(diphenyl)silyl]oxy]-4-penten-2-ol | C21H28O2Si | 详情 | 详情 | |
| (XXIX) | 42391 | (4R,6S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(iodomethyl)-1,3-dioxan-2-one | C22H27IO4Si | 详情 | 详情 | |
| (XXX) | 42392 | tert-butyl(diphenyl)silyl (1R)-2-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2S)oxiranylmethyl]ethyl ether; (5R)-2,2,9,9-tetramethyl-5-[(2S)oxiranylmethyl]-3,3,8,8-tetraphenyl-4,7-dioxa-3,8-disiladecane | C37H46O3Si2 | 详情 | 详情 | |
| (XXXI) | 42393 | (2S,4R)-4,5-bis[[tert-butyl(diphenyl)silyl]oxy]-1-[2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithian-2-yl]-2-pentanol | C47H64O4S2Si2 | 详情 | 详情 | |
| (XXXII) | 42394 | tert-butyl(diphenyl)silyl [(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methyl ether; tert-butyl([(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methoxy)diphenylsilane | C45H58O5Si2 | 详情 | 详情 | |
| (XXXIII) | 42395 | tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane | C28H47IO7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)Synthesis of intermediate (L): The condensation of aldehyde intermediate (XLIII) with iodovinyl intermediate (XXXIII) by means of NiCl2/CrCl2 bispyridinyl ligand in THF, followed by a treatment with DMP, gives the adduct (XLIV), which is treated with PPTS to yield the bis spiroketal (XLV) with undesired configuration at the new stereocenter. The treatment of (XLV) with HF/pyridine in acetonitrile gives rise to a desilylation of the TBDMS group with concomitant isomerization of the new stereocenter yielding a separable mixture of two diastereomers (XLVI) and (XLVII). Compound (XLVII) has the desired configuration, and (XLVI) can be recovered by isomerizing it again to the starting diastereomeric mixture. The silylation of (XLVII) with TBDMS-OTf, followed by selective monodesilylation of the primary OH group with HF/pyridine in THF, gives the ethanol derivative (XLVIII), which is oxidized with tetrapropylammonium perruthenate (TPAP) and NaClO2 and silylated with TBDPSCl to yield the silyl ester (XLIX). Finally, this compound is selectively deprotected with DDQ and oxidized with DMP to afford the desired aldehydic intermediate (L).
| 【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 |
|---|---|---|---|---|---|---|
| (XXXIII) | 42395 | tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane | C28H47IO7Si | 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 | |
| (XLIV) | 42405 | 2-((2S,4S,6R,8S,10S)-4-(acetoxy)-8-[(3R,4S,5S,7E,10S)-4-(acetoxy)-11-[(2R,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-2-yl]-10-methoxy-3,5-dimethyl-2-methylene-6-oxo-7-undeceny | C56H90O18Si | 详情 | 详情 | |
| (XLV) | 42406 | (2S,4S,6S,8S,10S)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-2-(2-hydrox | C52H84O16Si | 详情 | 详情 | |
| (XLVI) | 42407 | (1S,2R)-3-[[(2S,4S,6S,8S,10S)-10-(acetoxy)-4-hydroxy-8-(2-hydroxyethyl)-4-methyl-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-1-[(1S)-3-[(2S,4S,6R,8R,10S)-10-hydroxy-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1-met | C46H70O16 | 详情 | 详情 | |
| (XLVII) | 42408 | (1S,2R)-3-[[(2S,4S,6S,8S,10S)-10-(acetoxy)-4-hydroxy-8-(2-hydroxyethyl)-4-methyl-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-1-[(1S)-3-[(2S,4S,6S,8R,10S)-10-hydroxy-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1-met | C46H70O16 | 详情 | 详情 | |
| (XLVIII) | 42409 | (2S,4S,6S,8S,10S)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6R,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-2-(2-hydrox | C52H84O16Si | 详情 | 详情 | |
| (XLIX) | 42410 | tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6R,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-ox | C68H100O17Si2 | 详情 | 详情 | |
| (L) | 42411 | tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a | C53H74O14Si | 详情 | 详情 |