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【结 构 式】 
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【分子编号】69414 【品名】tert-butyl ((1S,2S)-1-hydroxy-4-methyl-1-(2-methyloxiran-2-yl)pentan-2-yl)carbamate 【CA登记号】 |
【 分 子 式 】C14H27NO4 【 分 子 量 】273.37272 【元素组成】C 61.51% H 9.96% N 5.12% O 23.41% |
合成路线1
该中间体在本合成路线中的序号：(XXXIIb)Condensation of N-Boc-leucine (X) with N,O-dimethylhydroxylamine hydrochloride by means of i-BuOCOCl, NMM and Et3N in CH2Cl2 gives N-Boc-L-leucine Weinreb amide (XXVII) , which is then coupled with isopropenyl magnesium bromide (XXVIII) in THF (1) or 2-bromopropene (XXIX) in the presence of BuLi in Et2O at –78 °C to yield the heptenone derivative (XXX) . Reduction of heptenone (XXX) with NaBH4 and CeCl3·7H2O in MeOH results in a diastereomeric mixture of allylic alcohols (XXXIa) and (XXXIb), which is then epoxidized by treatment with mCPBA in CH2Cl2 to afford a mixture of oxiranes (XXXIIa) and (XXXIIb). Finally, this mixture is oxidized with Dess Martin periodinane in acetonitrile, followed by chromatographic separation . Compound (XXVI) can also be prepared by epoxidation of heptenone derivative (XXX) with H2O2 in the presence of PhCN and DIEA in MeOH or NaOCl in pyridine or Ca(OCl)2 in NMP , followed by separation by means of column chromatography .
| 【2】 Sin, N., Kim, K.B., Elofsson, M., Meng, L., Auth, H., Kwok, B.H.B., Crews, C.M. Total synthesis of the potent proteasome inhibitor epoximicin: A useful tool for understanding proteosome biology. Bioorg Med Chem Lett 1999, 9(15): 2283-8. |
| 【1】 Phiasivongsa, P., Sehl, L.C., Fuller, W.D., Laidig, G.J. (Proteolix, Inc.). Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides. WO 2009045497. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIa) | 69411 | tert-butyl ((3S,4R)-3-hydroxy-2,6-dimethylhept-1-en-4-yl)carbamate | C14H27NO3 | 详情 | 详情 | |
| (XXXIb) | 69412 | tert-butyl ((3R,4R)-3-hydroxy-2,6-dimethylhept-1-en-4-yl)carbamate | C14H27NO3 | 详情 | 详情 | |
| (XXXIIa) | 69413 | tert-butyl ((1R,2S)-1-hydroxy-4-methyl-1-(2-methyloxiran-2-yl)pentan-2-yl)carbamate | C14H27NO4 | 详情 | 详情 | |
| (XXXIIb) | 69414 | tert-butyl ((1S,2S)-1-hydroxy-4-methyl-1-(2-methyloxiran-2-yl)pentan-2-yl)carbamate | C14H27NO4 | 详情 | 详情 | |
| (X) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (XXVI) | 43028 | tert-butyl ((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)carbamate；tert-butyl (1S)-3-methyl-1-[[(2R)-2-methyloxiranyl]carbonyl]butylcarbamate | C14H25NO4 | 详情 | 详情 | |
| (XXVII) | 40395 | tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-methylbutylcarbamate | C13H26N2O4 | 详情 | 详情 | |
| (XXVIII) | 43649 | bromo(isopropenyl)magnesium；isopropenyl magnesium bromide；1-Methylvinylmagnesiumbromide;1-Propen-2-ylmagnesium bromide;a-Methylvinylmagnesium bromide | 13291-18-4 | C3H5BrMg | 详情 | 详情 |
| (XXIX) | 42375 | 2-bromo-1-propene；2-bromopropene;Isopropenyl bromide;a-Methylvinyl bromide | 557-93-7 | C3H5Br | 详情 | 详情 |
| (XXX) | 43027 | tert-butyl (1S)-1-isobutyl-3-methyl-2-oxo-3-butenylcarbamate | C14H25NO3 | 详情 | 详情 |