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【结 构 式】 
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【分子编号】52400 【品名】 【CA登记号】 |
【 分 子 式 】C70H131IO13Si5 【 分 子 量 】1448.13431 【元素组成】C 58.06% H 9.12% I 8.76% O 14.36% Si 9.7% |
合成路线1
该中间体在本合成路线中的序号：(XXXVIII)The aldehyde building block (XXXV) was obtained by DIBAL reduction of the previously described methyl ester (XXXIV). Lithiation of alkyl iodide (XXXIII) by means of tert-BuLi and then addition to aldehyde (XXXV) furnished the carbinol adduct (XXXVI). The methoxytrityl protecting group of (XXXVI) was then removed by acidic treatment, yielding (XXXVII). Oxidation of both free hydroxyl groups of (XXXVII) with Dess-Martin periodinane reagent gave rise to the keto aldehyde (XXXVIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 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) | 52396 | C59H89IO8Si2 | 详情 | 详情 | ||
| (XXXIV) | 48420 | methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate | C32H63IO7Si3 | 详情 | 详情 | |
| (XXXV) | 52397 | C31H61IO6Si3 | 详情 | 详情 | ||
| (XXXVI) | 52398 | C90H151IO14Si5 | 详情 | 详情 | ||
| (XXXVII) | 52399 | C70H135IO13Si5 | 详情 | 详情 | ||
| (XXXVIII) | 52400 | C70H131IO13Si5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVIII)Dess-Martin oxidation of both alcohol functions of (XLIII) yielded the keto sulfone (XLIV). Reductive cleavage of the phenylsulfonyl group (XLIV) to afford (XXXVIII) was carried out by means of an in situ-generated SmI2 solution in THF.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
合成路线3
该中间体在本合成路线中的序号：(XXXVIII)Cyclization between the aldehyde and vinyl iodide moieties of (XXXVIII) was achieved by NiCl2/CrCl2-promoted intramolecular condensation. The resulting macrocyclic alcohol (XLV) was then oxidized to ketone (XLVI) with Dess-Martin periodinane reagent. Deprotection of (XLVI) with tetrabutylammonium fluoride furnished the fully desilylated compound (XLVII). The final cyclization between hydroxyl groups and the unsaturated ketone group of (XLVII) under acidic conditions gave rise to the title compound.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
合成路线4
该中间体在本合成路线中的序号：(XXXVIII)The aldehyde building block (XXXV) was obtained by DIBAL reduction of the previously described methyl ester (XXXIV). Lithiation of alkyl iodide (XXXIII) by means of tert-BuLi and then addition to aldehyde (XXXV) furnished the carbinol adduct (XXXVI). The methoxytrityl protecting group of (XXXVI) was then removed by acidic treatment, yielding (XXXVII). Oxidation of both free hydroxyl groups of (XXXVII) with Dess-Martin periodinane reagent gave rise to the keto aldehyde (XXXVIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 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) | 52396 | C59H89IO8Si2 | 详情 | 详情 | ||
| (XXXIV) | 48420 | methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate | C32H63IO7Si3 | 详情 | 详情 | |
| (XXXV) | 52397 | C31H61IO6Si3 | 详情 | 详情 | ||
| (XXXVI) | 52398 | C90H151IO14Si5 | 详情 | 详情 | ||
| (XXXVII) | 52399 | C70H135IO13Si5 | 详情 | 详情 | ||
| (XXXVIII) | 52400 | C70H131IO13Si5 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XXXVIII)Dess-Martin oxidation of both alcohol functions of (XLIII) yielded the keto sulfone (XLIV). Reductive cleavage of the phenylsulfonyl group of (XLIV) to afford (XXXVIII) was carried out by means of an in situ-generated SmI2 solution in THF.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
合成路线6
该中间体在本合成路线中的序号：(XXXVIII)Cyclization between the aldehyde and vinyl iodide moieties of (XXXVIII) was achieved by NiCl2/CrCl2-promoted intramolecular condensation. The resulting macrocyclic alcohol (XLV) was then oxidized to ketone (XLVI) with Dess-Martin periodinane reagent. Deprotection of (XLVI) with tetrabutylammonium fluoride furnished the fully desilylated compound (XLVII). Then, cyclization between hydroxyl groups and the unsaturated ketone groups of (XLVII) under acidic conditions gave rise to the polycyclic compound (XLVIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLVa) | 52407 | C70H132O13Si5 | 详情 | 详情 | ||
| (XLVb) | 52408 | C70H132O13Si5 | 详情 | 详情 | ||
| (XXXVIII) | 52400 | C70H131IO13Si5 | 详情 | 详情 | ||
| (XLVI) | 52409 | C70H130O13Si5 | 详情 | 详情 | ||
| (XLVII) | 52410 | C40H60O13 | 详情 | 详情 | ||
| (XLVIII) | 52424 | 20-(2,3-dihydroxypropyl)-14-methyl-8,15-dimethylidene-21-(methyloxy)-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1~3,32~.1~3,33~.1~6,9~.1~12,16~.0~18,22~.0~29,36~.0~31,35~]hentetracontan-24-one | C40H58O12 | 详情 | 详情 |