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【结 构 式】 
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【分子编号】42797 【品名】2,2,2-trichloroethyl (10S,13S,15E,19R)-19-(3-chloro-4-methoxybenzyl)-13-[(1R,2R,3R)-2,3-dihydroxy-1-methyl-3-phenylpropyl]-10-isobutyl-2,2,7,7-tetramethyl-4,8,11,17-tetraoxo-3,9,12-trioxa-5,18-diaza-15-icosen-20-oate 【CA登记号】 |
【 分 子 式 】C43H58Cl4N2O12 【 分 子 量 】936.7506 【元素组成】C 55.13% H 6.24% Cl 15.14% N 2.99% O 20.5% |
合成路线1
该中间体在本合成路线中的序号：(II)The previously reported open-chain styrene intermediate (I) is submitted to a Sharpless asymmetric epoxidation to give, after chromatographic purification, the diol (II), which is cyclized by means of TFA and 2-hydroxypyridine yielding the macrocycle (III). The reaction of (III) with trimethyl orthoformate and pyridinium p-toluenesulfonate (PPTS) in dichloromethane affords the cyclic orthoester (IV), which is treated with trimethylsilyl iodide to provide the iodo formate (V). Finally, this compound is converted into the target macrocyclic epoxide by treatment with K2CO3 in methanol/THF. Alternatively, the intermediate cyclic orthoester (IV) can be treated with acetyl bromide to give the bromo formate (VI), which is converted into the target epoxide by reaction with K2CO3 as before.
| 【1】 WO 9640184 . |
| 【2】 Liang, J.; et al.; Synthesis of cryptophycin 52 using the Sharpless asymetric dihydroxylation: Diol to epoxide transformation optimized for a base-sensitive substrate. J Org Chem 2000, 65, 10, 3143. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18906 | 2,2,2-trichloroethyl (10S,13S,15E,19R)-19-(3-chloro-4-methoxybenzyl)-10-isobutyl-2,2,7,7-tetramethyl-13-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-4,8,11,17-tetraoxo-3,9,12-trioxa-5,18-diaza-15-icosen-20-oate | C43H56Cl4N2O10 | 详情 | 详情 | |
| (II) | 42797 | 2,2,2-trichloroethyl (10S,13S,15E,19R)-19-(3-chloro-4-methoxybenzyl)-13-[(1R,2R,3R)-2,3-dihydroxy-1-methyl-3-phenylpropyl]-10-isobutyl-2,2,7,7-tetramethyl-4,8,11,17-tetraoxo-3,9,12-trioxa-5,18-diaza-15-icosen-20-oate | C43H58Cl4N2O12 | 详情 | 详情 | |
| (III) | 42798 | (3S,10R,16S)-10-(3-chloro-4-methoxybenzyl)-16-[(1R,2R,3R)-2,3-dihydroxy-1-methyl-3-phenylpropyl]-3-isobutyl-6,6-dimethyl-1,4-dioxa-8,11-diaza-13-cyclohexadecene-2,5,9,12-tetrone | C36H47ClN2O9 | 详情 | 详情 | |
| (IV) | 42799 | (3S,10R,16S)-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-16-[(1R)-1-[(4R,5R)-2-methoxy-5-phenyl-1,3-dioxolan-4-yl]ethyl]-6,6-dimethyl-1,4-dioxa-8,11-diaza-13-cyclohexadecene-2,5,9,12-tetrone | C38H49ClN2O10 | 详情 | 详情 | |
| (V) | 42800 | (1R,2R)-2-[(3S,10R,16S)-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-2,5,9,12-tetraoxo-1,4-dioxa-8,11-diaza-13-cyclohexadecen-16-yl]-1-[(S)-iodo(phenyl)methyl]propyl formate | C37H46ClIN2O9 | 详情 | 详情 | |
| (VI) | 42801 | (1R,2R)-1-[(S)-bromo(phenyl)methyl]-2-[(3S,10R,16S)-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-2,5,9,12-tetraoxo-1,4-dioxa-8,11-diaza-13-cyclohexadecen-16-yl]propyl formate | C37H46BrClN2O9 | 详情 | 详情 |