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【结 构 式】 
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【分子编号】41170 【品名】6-aminohexanoic acid 【CA登记号】60-32-2 |
【 分 子 式 】C6H13NO2 【 分 子 量 】131.17476 【元素组成】C 54.94% H 9.99% N 10.68% O 24.39% |
合成路线1
该中间体在本合成路线中的序号：(I)The target product is obtained by phosphorylation of aminocaproic acid (I) by reflux with PCl3 / phosphorous acid (H3PO3) (directly or in chlorobenzene), followed by hydrolysis with boiling H2O.
| 【1】 US 4304734 . |
| 【2】 Guainai-Ricci, G.; Rosini, S. (Istituto Gentili SpA); Process for the preparation of diphosphonic acids and salts thereof. EP 0494844 . |
| 【3】 Blum, H.; Worms, K.-H. (Henkel KgA); Process for the production of omega-amino-1-hydroxyalkylidene-1,1-bisphosphonic acid. US 4407761 . |
| 【4】 Staibano, G. (Istituto Gentili SpA); Process for the preparation of diphosphonic acids. US 4705651 . |
合成路线2
该中间体在本合成路线中的序号：(XII)Derivative (VIII) is obtained as follows: Activation of protected aminoacid (IX) with DCC/HOSu and coupling with H-Arg(Pmc)-OH (A) yields carboxylic acid derivative (X) which is converted to methyl ester (XI). Catalytic hydrogenation of (XI) and coupling with the protected caproic acid (XII) in presence of DCC and HOSu provides derivative (XIII) which is finally catalytically hydrogenated yielding intermediate (VIII).
| 【1】 Guedj, R.; Peytou, V.; Aubertin, A.-M.; Terreux, R.; Bailly, C.; Patino, N.; Condom, R.; Cabrol-Bass, D.; Gelus, N.; Synthesis and antiviral activity of ethidium - Arginine conjugates directed against the TAR RNA of HIV-1. J Med Chem 1999, 42, 20, 4042. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII),(VIII) | 41166 | methyl (2S)-2-([3-[(6-aminohexanoyl)amino]propanoyl]amino)-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoate | C30H52N6O7S | 详情 | 详情 | |
| (A) | 41167 | (2S)-2-amino-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyric acid | C19H32N4O5S | 详情 | 详情 | |
| (IX) | 17022 | beta-Alanine; 3-aminopropionic acid | 107-95-9 | C3H7NO2 | 详情 | 详情 |
| (X) | 41168 | (2S)-2-[(3-aminopropanoyl)amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid | C23H39N5O6S | 详情 | 详情 | |
| (XI) | 41169 | methyl (2S)-2-[(3-aminopropanoyl)amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoate | C24H41N5O6S | 详情 | 详情 | |
| (XII) | 41170 | 6-aminohexanoic acid | 60-32-2 | C6H13NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)6-Aminocaproic acid (I) is condensed with maleic anhydride (II) in refluxing AcOH to provide maleimidocaproic acid (III). After activation of acid (III) as the corresponding mixed anhydride with isobutyl chloroformate, coupling with tert-butyl carbazate (IV) affords the N-Boc hydrazide (V). Subsequent acidic cleavage of the Boc group of (V) furnishes hydrazide (VI). Finally, hydrazide (VI) is condensed with doxorubicin (VII) to produce the title hydrazone conjugate.
| 【1】 Willner, D.; Trail, P.A.; Hofstead, S.J.; King, H.D.; Lasch, S.J.; Braslawsky, G.R.; Greenfield, R.S.; Kaneko, T.; Firestone, R.A.; (6-Maleimidocaproyl)hydrazone of doxorubicin - A new derivative for the preparation of immunoconjugates of doxorubicin. Bioconjugate Chem 1993, 4, 6, 521. |
| 【2】 Willner, D.; Trail, P.A.; King, D.H.; Hofstead, S.J.; Greenfield, R.S.; Braslawsky, G.R. (Bristol-Myers Squibb Co.); Thioether conjugates. EP 0554708; JP 1994025012; US 5622929 . |
| 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) | 41170 | 6-aminohexanoic acid | 60-32-2 | C6H13NO2 | 详情 | 详情 |
| (II) | 11182 | 2,5-Furandione; Maleic anhydride | 108-31-6 | C4H2O3 | 详情 | 详情 |
| (III) | 63203 | 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoic acid | C10H13NO4 | 详情 | 详情 | |
| (IV) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (V) | 63204 | tert-butyl 2-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-1-hydrazinecarboxylate | C15H23N3O5 | 详情 | 详情 | |
| (VI) | 63205 | 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanohydrazide | C10H15N3O3 | 详情 | 详情 | |
| (VII) | 11675 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-glycoloyl-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H29NO11 | 详情 | 详情 |