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【结 构 式】 
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【分子编号】39517 【品名】N-(benzyloxy)-4-methylbenzenesulfonamide 【CA登记号】 |
【 分 子 式 】C14H15NO3S 【 分 子 量 】277.34404 【元素组成】C 60.63% H 5.45% N 5.05% O 17.31% S 11.56% |
合成路线1
该中间体在本合成路线中的序号：(A)Ethyl 2,3-dibromopropionate (I) is condensed with N-tosyl-O-benzylhydroxylamine (A) by means of NaOEt in ethanol to give after a treatment with ammonia, propionic acid (II), which is detosylated by treatment with phenol and 36% HBr- yielding D,L-2-amino-3-(benzyloxyamino)propionic acid (III). The benzoylation of (III) with N-benzoyloxysuccinimide (B) by means of Triton B - in methanol affords D,L-2-benzoylamino-3-benzyloxyaminopropionic acid (IV), which is resolved into its optical isomers by treatment with aniline (C) and papain in 0.5M NaOH - 0.5M citric acid and L-cysteine hydrochloride; L-2-benzoylamino-3-benzyloxyaminopropionanilide (L)-(V) was isolated. The benzoylation of (L)-(V) with benzoyl chloride (D) in pyridine affords L-2-benzoylamino-3-(N-benzoyl-N-benzyloxyamino)propionanilide (L)-(VI), which is debenzylated by hydrogenation with H2 over Pd/C in methanol giving L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionanilide (L)-(VII). The protecting groups of (L)-(VII) are eliminated by treatment with 6M HCl at 90-5 C yielding L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII), which is finally nitrosated with NaNO2 and HCl.
| 【1】 Serradell, M.N.; Castañer, J.; Cabanillas, F.; Blancafort, P.; Alanosine. Drugs Fut 1979, 4, 7, 469. |
| 【2】 Yoshikazu, I.; et al.; Synthesis of alanosine. Bull Chem Soc Jpn 1973, 46, 1847-50. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (D) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (A) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (B) | 39520 | 1-(benzoyloxy)-2,5-pyrrolidinedione | C11H9NO4 | 详情 | 详情 | |
| (L)-(V) | 39522 | N-((1S)-2-anilino-1-[[(benzyloxy)amino]methyl]-2-oxoethyl)benzamide | C23H23N3O3 | 详情 | 详情 | |
| (L)-(VI) | 39523 | N-[(2S)-3-anilino-3-oxo-2-(propionylamino)propyl]-N-(benzyloxy)benzamide | C26H27N3O4 | 详情 | 详情 | |
| (L)-(VII) | 39524 | N-((1S)-2-anilino-1-[[benzoyl(hydroxy)amino]methyl]-2-oxoethyl)benzamide | C23H21N3O4 | 详情 | 详情 | |
| (L)-(VIII) | 39525 | (2S)-2-amino-3-(hydroxyamino)propionic acid | C3H8N2O3 | 详情 | 详情 | |
| (I) | 18341 | ethyl 2,3-dibromopropanoate | 3674-13-3 | C5H8Br2O2 | 详情 | 详情 |
| (II) | 39518 | 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]alanine | C17H20N2O5S | 详情 | 详情 | |
| (III) | 39519 | 3-[(benzyloxy)amino]alanine | C10H14N2O3 | 详情 | 详情 | |
| (IV) | 39521 | N-benzoyl-3-[(benzyloxy)amino]alanine | C17H18N2O4 | 详情 | 详情 | |
| (C) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The title compound was originally isolated from the fermentation broths of Streptomyces rubellomurinus. The chemical synthesis of this compound was further described. Treatment of O-benzyl hydroxylamine (I) with TsCl in pyridine afforded N-(benzyloxy)-p-toluenesulfonamide (II). A closely related procedure used O-(p-methoxy-benzyl)hydroxylamine. Diethyl (3-bromopropyl)phosphonate (V) was obtained by alkylation of the sodium salt of diethyl phosphonate (III) with 1,3-dibromopropane (IV). Related procedures used dibutyl phosphonate or 1-bromo-3-chloropropane instead of (III) or (IV). The condensation of protected hydroxylamine (II) with bromide (V) in the presence of NaH furnished adduct (VI). Alternatively, intermediate (VI) was prepared by first alkylation of N-(benzyloxy)-p-toluenesulfonamide (II) with 1,3-dibromopropane (IV) to give (VII), and then condensation of bromide (VII) with the sodium salt of diethyl phosphonate (III). Hydrolysis of (VI) with HCl in HOAc gave rise to 3-(N-hydroxyamino)propylphosphonic acid (VIII). This was finally acetylated with Ac2O in NaOH.
| 【1】 Takashi, K.; et al.; Studies on phosphonic acid antibiotics. I. Structure and synthesis 3-(N-acetyl-N-hydroxyamino) propylphosphonic acid (FR-900098) and its N-formyl analog (FR-31564). Tetrahedron Lett 1980, 21, 1, 95. |
| 【2】 Iguchi, E.; et al.; Studies on new phosphonic acid antibiotics II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds. J Antibiot 1980, 33, 1, 18. |
| 【3】 Takeno, H.; Hemmi, K.; Hashimoto, M.; Kamiya, T. (Fujisawa Pharmaceutical Co., Ltd.); Hydroxyaminohydrocarbonphosphonic acids. DE 2733658; US 4182758; US 4206156 . |
| 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) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (II) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (III) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (IV) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (V) | 39080 | diethyl 3-bromopropylphosphonate | C7H16BrO3P | 详情 | 详情 | |
| (VI) | 39104 | diethyl 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]propylphosphonate | C21H30NO6PS | 详情 | 详情 | |
| (VII) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (VIII) | 39088 | 3-(hydroxyamino)propylphosphonic acid | C3H10NO4P | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)The title compound was originally isolated from the fermentation broths of Streptomyces rubellomurinus. The chemical synthesis of this compound was further described. Treatment of O-benzyl hydroxylamine (I) with TsCl in pyridine afforded N-(benzyloxy)-p-toluenesulfonamide (II). A closely related procedure used O-(p-methoxy-benzyl)hydroxylamine. Diethyl (3-bromopropyl)phosphonate (V) was obtained by alkylation of the sodium salt of diethyl phosphonate (III) with 1,3-dibromopropane (IV). Related procedures used dibutyl phosphonate or 1-bromo-3-chloropropane instead of (III) or (IV). The condensation of protected hydroxylamine (II) with bromide (V) in the presence of NaH furnished adduct (VI). Alternatively, intermediate (VI) was prepared by first alkylation of N-(benzyloxy)-p-toluenesulfonamide (II) with 1,3-dibromopropane (IV) to give (VII), and then condensation of bromide (VII) with the sodium salt of diethyl phosphonate (III). Hydrolysis of (VI) with HCl in HOAc gave rise to 3-(N-hydroxyamino)propylphosphonic acid (VIII). This was finally acetylated with Ac2O in NaOH.
| 【1】 Takashi, K.; et al.; Studies on phosphonic acid antibiotics. I. Structure and synthesis 3-(N-acetyl-N-hydroxyamino) propylphosphonic acid (FR-900098) and its N-formyl analog (FR-31564). Tetrahedron Lett 1980, 21, 1, 95. |
| 【2】 Iguchi, E.; et al.; Studies on new phosphonic acid antibiotics II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds. J Antibiot 1980, 33, 1, 18. |
| 【3】 Takeno, H.; Hemmi, K.; Hashimoto, M.; Kamiya, T. (Fujisawa Pharmaceutical Co., Ltd.); Hydroxyaminohydrocarbonphosphonic acids. DE 2733658; US 4182758; US 4206156 . |
| 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) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (II) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (III) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (IV) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (V) | 39080 | diethyl 3-bromopropylphosphonate | C7H16BrO3P | 详情 | 详情 | |
| (VI) | 39104 | diethyl 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]propylphosphonate | C21H30NO6PS | 详情 | 详情 | |
| (VII) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (VIII) | 39088 | 3-(hydroxyamino)propylphosphonic acid | C3H10NO4P | 详情 | 详情 |