【结 构 式】 |
【分子编号】26160 【品名】tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate 【CA登记号】 |
【 分 子 式 】C31H40NO6PSi 【 分 子 量 】581.721002 【元素组成】C 64.01% H 6.93% N 2.41% O 16.5% P 5.32% Si 4.83% |
合成路线1
该中间体在本合成路线中的序号:(II)Reaction of N-acetyl-L-tyrosine (I) with tert-butyldimethylsilyl chloride and N-methylmorpholine (NMM), followed by phosphitylation with dibenzyldiisopropylamine phosphoramidite produced the intermediate phosphite ester (II), which was oxidized to phosphate (III) using tert-butyl hydroperoxide. Subsequent coupling of (III) with protected glutamic acid (IV) in the presence of DCC and HOBt afforded dipeptide (V). Deprotection of the allyl ester of (V) by means of Pd(PPh3)4 and pyrrolidine provided acid (VI). After conversion of (VI) to the corresponding mixed anhydride with isobutyl chloroformate, condensation with 4-methoxybenzyl amine (VII) yielded amide (VIII). Finally, the benzyl ester groups were eliminated by catalytic hydrogenation over Pd/C (1).
【1】 Llinas-Brunet, M.; et al.; Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain. J Med Chem 1999, 42, 4, 722. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
40669 | C17H22NO2P | 详情 | 详情 | |||
(I) | 26159 | N-Acetyl-L-tyrosine; (2S)-2-(acetamido)-3-(4-hydroxyphenyl)propionic acid | 537-55-3 | C11H13NO4 | 详情 | 详情 |
(II) | 26160 | tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate | C31H40NO6PSi | 详情 | 详情 | |
(III) | 26161 | (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid | C25H26NO7P | 详情 | 详情 | |
(IV) | 26162 | 1-allyl 5-benzyl (2S)-2-aminopentanedioate | C15H19NO4 | 详情 | 详情 | |
(V) | 26163 | 1-allyl 5-benzyl (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]pentanedioate | C40H43N2O10P | 详情 | 详情 | |
(VI) | 26164 | (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-5-(benzyloxy)-5-oxopentanoic acid | C37H39N2O10P | 详情 | 详情 | |
(VII) | 15098 | 4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine | 2393-23-9 | C8H11NO | 详情 | 详情 |
(VIII) | 26165 | benzyl (4S)-4-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-5-[(4-methoxybenzyl)amino]-5-oxopentanoate | C45H48N3O10P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(IX)Reaction of N-acetyl-L-tyrosine (VIII) with tert-butyldimethylsilyl chloride and N-methylmorpholine (NMM), followed by phosphitylation with dibenzyldiisopropylamine phosphoramidite produced the intermediate phosphite ester (IX), which was oxidized to phosphate (X) using tert-butyl hydroperoxide. Subsequent coupling of (X) with protected leucine (XI) in the presence of DCC and HOBt afforded dipeptide (XII). Deprotection of the allyl ester of (XII) by means of Pd(PPh3)4 and pyrrolidine provided acid (XIII). After conversion of (XIII) to the corresponding mixed anhydride with isobutyl chloroformate, condensation with the chiral amine (VII) yielded amide (XIV). Finally, the benzyl ester groups of (XIV) were eliminated by catalytic hydrogenation over Pd/C.
【1】 Llinas-Brunet, M.; et al.; Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain. J Med Chem 1999, 42, 4, 722. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
40669 | C17H22NO2P | 详情 | 详情 | |||
(VII) | 26171 | (1S)-1-(4-isopropylphenyl)ethylamine; (1S)-1-(4-isopropylphenyl)-1-ethanamine | C11H17N | 详情 | 详情 | |
(VIII) | 26159 | N-Acetyl-L-tyrosine; (2S)-2-(acetamido)-3-(4-hydroxyphenyl)propionic acid | 537-55-3 | C11H13NO4 | 详情 | 详情 |
(IX) | 26160 | tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate | C31H40NO6PSi | 详情 | 详情 | |
(X) | 26161 | (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid | C25H26NO7P | 详情 | 详情 | |
(XI) | 26172 | allyl (2S)-2-amino-4-methylpentanoate | C9H17NO2 | 详情 | 详情 | |
(XII) | 26173 | allyl (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-4-methylpentanoate | C34H41N2O8P | 详情 | 详情 | |
(XIII) | 26174 | (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-4-methylpentanoic acid | C31H37N2O8P | 详情 | 详情 | |
(XIV) | 26175 | 4-((2S)-2-(acetamido)-3-[[(1S)-1-([[(1S)-1-(4-isopropylphenyl)ethyl]amino]carbonyl)-3-methylbutyl]amino]-3-oxopropyl)phenyl dibenzyl phosphate | C42H52N3O7P | 详情 | 详情 |