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【结 构 式】 
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【分子编号】60426 【品名】ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-iodo-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate 【CA登记号】 |
【 分 子 式 】C43H80BrIO6Si3 【 分 子 量 】984.16957 【元素组成】C 52.48% H 8.19% Br 8.12% I 12.89% O 9.75% Si 8.56% |
合成路线1
该中间体在本合成路线中的序号：(XXI)Suzuki coupling of vinyl bromide (VIII) with boronic acid (XVI) gives bromotetraene (XVII). The methoxyamide function of (XVII) is then reduced to aldehyde (XVIII) employing DIBAL in THF. Two carbon homologation of aldehyde (XVIII) with ethyl diazoacetate leads to keto ester (XIX). Selective removal of the primary tert-butyl diphenylsilyl ether of (XIX) with tetrabutylammonium fluoride affords the allylic alcohol (XX), which is then converted into iodide (XXI) by means of I2 and PPh3.
| 【1】 Evans, D.A.; Starr, J.T.; A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem. Int Ed 2002, 41, 10, 1787. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 15911 | Ethyldiazoacetate; ethyl 2-diazoacetate | 623-73-4 | C4H6N2O2 | 详情 | 详情 |
| (VIII) | 60352 | 10,10-dibromo-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N,2,6-trimethyl-N-(methyloxy)-6,9-decadienamide | C20H37Br2NO3Si | 详情 | 详情 | |
| (XVI) | 60358 | 3,5-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-8-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4-methyl-1,6-octadienylboronic acid | C37H63BO5Si3 | 详情 | 详情 | |
| (XVII) | 60422 | 10-bromo-3,13,15-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-18-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-N,2,6,14-tetramethyl-N-(methyloxy)-6,9,11,16-octadecatetraenamide | C57H98BrNO6Si4 | 详情 | 详情 | |
| (XVIII) | 60423 | 10-bromo-3,13,15-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-18-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2,6,14-trimethyl-6,9,11,16-octadecatetraenal | C55H93BrO5Si4 | 详情 | 详情 | |
| (XIX) | 60424 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C59H99BrO7Si4 | 详情 | 详情 | |
| (XX) | 60425 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-hydroxy-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C43H81BrO7Si3 | 详情 | 详情 | |
| (XXI) | 60426 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-iodo-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C43H80BrIO6Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXI)Intramolecular cyclization of iodide (XXI) in the presence of Cs2CO3 provides macrocycle (XXII) as an epimeric mixture. Oxidation of (XXII) with Ph2Se2O3 gives rise to the conjugated ester (XXIII), which spontaneously undergoes a sequence of transannular cycloadditions culminating in the formation of the polycyclic compound (XXIV). Complete desilylation of (XXIV) to yield (XXV) is carried out by means of HF in acetonitrile. Methylation of the vinylic bromide of (XXV) by employing trimethylboroxine under Suzuki conditions leads to (XXVI). After hydrolysis of the ethyl ester of (XXVI) under anhydrous conditions, the resultant carboxylic acid (XXVII) is finally subjected to lactonization in the presence of Mukaiyama's reagent (XXVIII) to furnish the title compound.
| 【1】 Evans, D.A.; Starr, J.T.; A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem. Int Ed 2002, 41, 10, 1787. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 60426 | ethyl 12-bromo-5,15,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-20-iodo-4,8,16-trimethyl-3-oxo-8,11,13,18-icosatetraenoate | C43H80BrIO6Si3 | 详情 | 详情 | |
| (XXII) | 60427 | ethyl 10-bromo-5,7,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-6,14,18-trimethyl-19-oxo-3,8,10,13-cyclononadecatetraene-1-carboxylate | C43H79BrO6Si3 | 详情 | 详情 | |
| (XXIII) | 60428 | ethyl 10-bromo-5,7,17-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-6,14,18-trimethyl-19-oxo-1,3,8,10,13-cyclononadecapentaene-1-carboxylate | C43H77BrO6Si3 | 详情 | 详情 | |
| (XXIV) | 60429 | ethyl (1S,2R,4R,7S,8R,9R,10S,11R,12R,13S,16R,17S)-5-bromo-8,10,17-tris{[tert-butyl(dimethyl)silyl]oxy}-1,9,16-trimethyl-20-oxapentacyclo[13.4.1.0~2,13~.0~4,12~.0~7,11~]icosa-5,14-diene-14-carboxylate | C43H77BrO6Si3 | 详情 | 详情 | |
| (XXV) | 60430 | ethyl (1S,2R,4R,7S,8R,9R,10S,11R,12R,13S,16R,17S)-5-bromo-8,10,17-trihydroxy-1,9,16-trimethyl-20-oxapentacyclo[13.4.1.0~2,13~.0~4,12~.0~7,11~]icosa-5,14-diene-14-carboxylate | C25H35BrO6 | 详情 | 详情 | |
| (XXVI) | 60431 | ethyl (1S,2R,4R,7R,8R,9S,10S,11R,12R,13S,16R,17S)-8,10,17-trihydroxy-1,5,9,16-tetramethyl-20-oxapentacyclo[13.4.1.0~2,13~.0~4,12~.0~7,11~]icosa-5,14-diene-14-carboxylate | C26H38O6 | 详情 | 详情 | |
| (XXVII) | 60432 | (1S,2R,4R,7R,8R,9S,10S,11R,12R,13S,16R,17S)-8,10,17-trihydroxy-1,5,9,16-tetramethyl-20-oxapentacyclo[13.4.1.0~2,13~.0~4,12~.0~7,11~]icosa-5,14-diene-14-carboxylic acid | C24H34O6 | 详情 | 详情 | |
| (XXVIII) | 60433 | 2-chloro-1-methylpyridinium | C6H7ClN | 详情 | 详情 |