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【结 构 式】 
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【分子编号】50804 【品名】2-(trimethylsilyl)ethyl (2S,3R)-2-amino-3-hydroxybutanoate 【CA登记号】 |
【 分 子 式 】C9H21NO3Si 【 分 子 量 】219.35618 【元素组成】C 49.28% H 9.65% N 6.39% O 21.88% Si 12.8% |
合成路线1
该中间体在本合成路线中的序号：(VII)Coupling of benzyloxy isovalery propionic acid (Bzl-Hip-OH) (I) with leucine trimethylsilylethyl ester (II) by means of HOBt and DCC followed by hydrogenation over Pd/C in isopropanol for benzyl protecting group removal provides dipeptide (III), which is then converted into compound (V) by first coupling to Boc-Sta(TBDMS)-OH (IV) by means of DMAP and DCC followed by removal of the TMSe group by means of TBAF. Coupling between Z-D-N-MeLeu-OH (VI) and H-Thr-OTMSe (VII) by means of N-hydroxysuccinimide (NHS) and EDC yields protected dipeptide (VIII), which is then condensed with dipeptide (IX) by means of DMAP and DCC and then treated with HCl in EtOAc for Boc removal to afford tetrapeptide (X) (in turn, dipeptide (IX) can be obtained by coupling between Boc-Pro-OH (XI) and Me2Tyr-ONb (XII) by means of EDC followed by p-nitrobenzyl removal by hydrogenation over Pd/C in HOAc). Coupling of tetrapeptide (X) with compound (V) by means of EDC, HOBt leads to formation of linear peptide (XIII), which is partially deprotected by treatment with TBAF and TFA and then cyclized by means of HOBt, EDC and NMM, providing macrolide (XIV).
| 【1】 Rinehart, K.L.; et al.; Total synthesis of didemnins A, B, and C. J Am Chem Soc 1987, 109, 22, 6846. |
| 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) | 50799 | (2S,4S)-4-(benzyloxy)-2,5-dimethyl-3-oxohexanoic acid | C15H20O4 | 详情 | 详情 | |
| (II) | 50800 | 2-(trimethylsilyl)ethyl (2S)-2-amino-4-methylpentanoate | C11H25NO2Si | 详情 | 详情 | |
| (III) | 50801 | 2-(trimethylsilyl)ethyl (2S)-2-[[(2S,4S)-4-hydroxy-2,5-dimethyl-3-oxohexanoyl]amino]-4-methylpentanoate | C19H37NO5Si | 详情 | 详情 | |
| (IV) | 50802 | (3S,4R,5S)-4-[(tert-butoxycarbonyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-methylheptanoic acid | C19H39NO5Si | 详情 | 详情 | |
| (V) | 50803 | (6R,7S,11S,13S,16S)-7-[[tert-butyl(dimethyl)silyl]oxy]-16-isobutyl-11-isopropyl-2,2,13-trimethyl-6-[(1S)-1-methylpropyl]-4,9,12,14-tetraoxo-3,10-dioxa-5,15-diazaheptadecan-17-oic acid | C33H62N2O9Si | 详情 | 详情 | |
| (VI) | 50772 | (2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoic acid | C15H21NO4 | 详情 | 详情 | |
| (VII) | 50804 | 2-(trimethylsilyl)ethyl (2S,3R)-2-amino-3-hydroxybutanoate | C9H21NO3Si | 详情 | 详情 | |
| (VIII) | 50805 | 2-(trimethylsilyl)ethyl (2S,3R)-2-([(2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoyl]amino)-3-hydroxybutanoate | C24H40N2O6Si | 详情 | 详情 | |
| (IX) | 50806 | (2S)-2-[[[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propionic acid | C21H30N2O6 | 详情 | 详情 | |
| (X) | 50807 | 2-(trimethylsilyl)ethyl (2S,3R)-2-([(2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoyl]amino)-3-[((2S)-3-(4-methoxyphenyl)-2-[methyl[(2S)pyrrolidinylcarbonyl]amino]propanoyl)oxy]butanoate | C40H60N4O9Si | 详情 | 详情 | |
| (XI) | 16734 | (2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid | C10H17NO4 | 详情 | 详情 | |
| (XII) | 50808 | C11H14NNbO3 | 详情 | 详情 | ||
| (XIII) | 50809 | 2-(trimethylsilyl)ethyl (2S,3R)-2-([(2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoyl]amino)-3-[[(2S)-2-[[((2S)-1-[(2S,5S,7S,11S,12R)-11-[[tert-butyl(dimethyl)silyl]oxy]-2-isobutyl-7-isopropyl-5,16,16-trimethyl-12-[(1S)-1-methylpropyl]-4 | C73H120N6O17Si2 | 详情 | 详情 | |
| (XIV) | 50810 | benzyl (1R)-1-[([(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin | C57H84N6O14 | 详情 | 详情 |