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【结 构 式】 
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【分子编号】56829 【品名】(2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid 【CA登记号】 |
【 分 子 式 】C19H26N8O6 【 分 子 量 】462.46576 【元素组成】C 49.35% H 5.67% N 24.23% O 20.76% |
合成路线1
该中间体在本合成路线中的序号：(XX)In a different synthetic strategy, L-serine methyl ester (X) was protected as the N-benzyl derivative (XI) by reductive alkylation with benzaldehyde and NaBH4. Ammonolysis of ester (XI) then produced N-benzyl serinamide (XII). Subsequent reduction of the amide function of (XII) employing borane-dimethyl sulfide complex gave diamine (XIII). This was condensed with the chloropyrimidine (XIV) to afford adduct (XV). After protection of the exocyclic amine with di-tert-butyl dicarbonate, alcohol (XVI) oxidation with Dess-Martin periodinane reagent yielded aldehyde (XVII). Reductive coupling of (XVII) with p-aminobenzoyl glutamic acid (XVIII), followed by acidic Boc group deprotection, led to the triaminopropane derivative (XIX). Catalytic hydrogenation of the nitro group of (XIX) and N-debenzylation over Pd/C yielded the pteridine ring precursor (XX).
| 【1】 Bailey, S.W.; et al.; Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid. J Org Chem 1992, 57, 16, 4470. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 20915 | methyl (2S)-2-amino-3-hydroxypropanoate | 5680-80-8 | C4H9NO3 | 详情 | 详情 |
| (XI) | 56820 | methyl (2S)-2-(benzylamino)-3-hydroxypropanoate | C11H15NO3 | 详情 | 详情 | |
| (XII) | 56821 | (2S)-2-(benzylamino)-3-hydroxypropanamide | C10H14N2O2 | 详情 | 详情 | |
| (XIII) | 56822 | (2R)-3-amino-2-(benzylamino)-1-propanol | C10H16N2O | 详情 | 详情 | |
| (XIV) | 56823 | 2-amino-6-chloro-5-nitro-4(1H)-pyrimidinone | C4H3ClN4O3 | 详情 | 详情 | |
| (XV) | 56824 | 2-amino-6-{[(2R)-2-(benzylamino)-3-hydroxypropyl]amino}-5-nitro-4(1H)-pyrimidinone | C14H18N6O4 | 详情 | 详情 | |
| (XVI) | 56825 | tert-butyl (1R)-2-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-1-(hydroxymethyl)ethyl(benzyl)carbamate | C19H26N6O6 | 详情 | 详情 | |
| (XVII) | 56826 | tert-butyl (1R)-2-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-1-formylethyl(benzyl)carbamate | C19H24N6O6 | 详情 | 详情 | |
| (XVIII) | 56827 | (2S)-2-[(4-aminobenzoyl)amino]pentanedioic acid | C12H14N2O5 | 详情 | 详情 | |
| (XIX) | 56828 | (2S)-2-[(4-{[(2S)-3-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-2-(benzylamino)propyl]amino}benzoyl)amino]pentanedioic acid | C26H30N8O8 | 详情 | 详情 | |
| (XX) | 56829 | (2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid | C19H26N8O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XX)Oxidation of the triamino pyrimidinone system (XX) by means of iodine produced the intermediate ortho-iminoquinone (XXI), which underwent hydrolysis to dione (XXII). Subsequent cyclization of (XXII) under controlled conditions led to the chiral tetrahydrofolic acid (VI). Finally, regioselective N5-formylation of (VI) was accomplished by treatment with formic acid and carbonyl diimidazole.
| 【1】 Bailey, S.W.; et al.; Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid. J Org Chem 1992, 57, 16, 4470. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 56817 | (2S)-2-{[4-({[(6S)-2-amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl]methyl}amino)benzoyl]amino}pentanedioic acid | C19H23N7O6 | 详情 | 详情 | |
| (XX) | 56829 | (2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid | C19H26N8O6 | 详情 | 详情 | |
| (XXI) | 56830 | (2S)-2-{[4-({(2S)-2-amino-3-[(2-amino-5-imino-6-oxo-5,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid | C19H24N8O6 | 详情 | 详情 | |
| (XXII) | 56831 | (2S)-2-{[4-({(2S)-2-amino-3-[(2-amino-5,6-dioxo-5,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid | C19H23N7O7 | 详情 | 详情 |