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【结 构 式】 
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【分子编号】61826 【品名】benzyl (2S)-4-amino-2-[((2S)-2-amino-3-{3-[(3S)-3-((1R,2R)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-hydroxyphenyl}propanoyl)amino]-4-oxobutanoate 【CA登记号】 |
【 分 子 式 】C39H41N5O11 【 分 子 量 】755.78164 【元素组成】C 61.98% H 5.47% N 9.27% O 23.29% |
合成路线1
该中间体在本合成路线中的序号：/XVI)The reaction of (XV) with TFA promotes the cleavage of the oxazolidine ring and the Boc and Mom protecting groups yielding the amino tetrahydroxy derivative (XVI), which is condensed with 3-methyl-2-oxopentanoic acid (XVII) by means of HOAt and EDC in THF to afford the corresponding amide (XVIII). The hydrogenolysis of (XVIII) with H2 over Pd/C in ethanol promotes the cleavage of the benzyloxy and benzyloxycarbonyl groups which provides the requisite aminoacid (XIX), suitable for macrocyclization. This is performed by means of EDC and HOAt in DMF/dichloromethane to provide the macrocyclic compound (XX). Finally, this compound is treated with Tes-OTf and lutidine in DMF/dichloromethane to obtain the fully silylated, already reported, macrocyclic intermediate (XXI). (see Scheme nos. 27460201c and 27460201d, intermediate (XXV).
| 【1】 Albrecht, B.K.; Williams, R.M.; A concise formal total synthesis of TMC-95A/B proteasome inhibitors. Org Lett 2003, 5, 2, 197. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| /XVI) | 61826 | benzyl (2S)-4-amino-2-[((2S)-2-amino-3-{3-[(3S)-3-((1R,2R)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-hydroxyphenyl}propanoyl)amino]-4-oxobutanoate | C39H41N5O11 | 详情 | 详情 | |
| (XV) | 61823 | benzyl (4R)-4-[(R)-{(3S)-7-[5-{(2S)-3-({(1S)-3-amino-1-[(benzyloxy)carbonyl]-3-oxopropyl}amino)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}-2-(methoxymethoxy)phenyl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl}(hydroxy)methyl]-2,2-dimethyl-1,3-oxazoli | C49H57N5O14 | 详情 | 详情 | |
| (XVIII) | 61827 | benzyl (2S)-4-amino-2-({(2S)-3-{3-[(3S)-3-((1R,2R)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-hydroxyphenyl}-2-[(3-methyl-2-oxopentanoyl)amino]propanoyl}amino)-4-oxobutanoate | C45H49N5O13 | 详情 | 详情 | |
| (XIX) | 61828 | (2S)-4-amino-2-({(2S)-3-(3-{(3S)-3-[(1R,2R)-2-amino-1,3-dihydroxypropyl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl}-4-hydroxyphenyl)-2-[(3-methyl-2-oxopentanoyl)amino]propanoyl}amino)-4-oxobutanoic acid | C30H37N5O11 | 详情 | 详情 | |
| (XX) | 53359 | N-[(10S,11R,12R,15S,18S)-15-(2-amino-2-oxoethyl)-10,11,23-trihydroxy-12-(hydroxymethyl)-9,14,17-trioxo-8,13,16-triazatetracyclo[18.3.1.0~2,7~.0~6,10~]tetracosa-1(24),2,4,6,20,22-hexaen-18-yl]-3-methyl-2-oxopentanamide | n/a | C30H35N5O10 | 详情 | 详情 |
| (XXI) | 53360 | N-[(10S,11R,12R,15S,18S)-15-(2-amino-2-oxoethyl)-9,14,17-trioxo-10,11,23-tris[(triethylsilyl)oxy]-12-{[(triethylsilyl)oxy]methyl}-8,13,16-triazatetracyclo[18.3.1.0~2,7~.0~6,10~]tetracosa-1(24),2,4,6,20,22-hexaen-18-yl]-3-methyl-2-oxopentanamide | n/a | C54H91N5O10Si4 | 详情 | 详情 |