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【结 构 式】 
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【分子编号】29999 【品名】(2R,3R,4S,5S,6R)-2-[[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-(isobutylamino)tetrahydro-2H-pyran-3-yl]oxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; Isobutylmaltosylamine 【CA登记号】 |
【 分 子 式 】C16H31NO10 【 分 子 量 】397.42288 【元素组成】C 48.36% H 7.86% N 3.52% O 40.26% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of maltose (I) with isobutylamine (II) in methanol at 65 C gives isobutylmaltosylamine (III), which is condensed with 2-chloroethyl isocyanate (IV) yielding 1-(2-chloroethyl)-3-isobutyl-3-D-maltosylurea (V). The nitrosation of (V) with dinitrogen tetroxide in THF in the presence of sodium acetate gives 1-(2-chloroethyl)-3-isobutyl-3-(beta-D-heptanitrosomaltosyl)-1-nitrosourea (VI). The nitrous esters of (VI) can be decomposed without affecting the N-nitroso group by addition of methanol under acidic conditions to give TA-077 in good yield.
| 【1】 Arai, Y.; Ozeki, M.; Morikawa, T.; Umino, N.; Kawamori, M.; Tsujihara, K.; A new class of nitrosoureas. III. Synthesis and antitumor activity of 3,3-disubstituted-1(2-chloroethyl)-1-nitrosoureas having a arabinopyranosyl, xylopyranosyl or ribopyranosyl moiety. Chem Pharm Bull 1982, 30, 534-543. |
| 【2】 Taga, M.; Morikawa, T.; Kawamori, M.; Ozeki, M.; Arai, Y.; Tsujihara, K.; Miyazaki, M.; A new class of nitrosoureas. II. Synthesis and antitumor activity of 1-(2-chloroehtyl)-3,3-disubstituted-1-nitrosoureas having a glucopyranosyl, mannopyranosyl or galactopyranosyl moiety. Chem Pharm Bull 1981, 29, 3262. |
| 【3】 Tsujihara, K.; Ozeki, M.; Arai, Y.; Morikawa, T.; Akaike, Y.; Kawamori, M.; A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas. J Med Chem 1982, 25, 4, 441-446. |
| 【4】 Fujimoto, S.; Ogawa, M.; TA-077. Drugs Fut 1984, 9, 2, 126. |
| 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) | 29998 | (3R,4R,5S,6R)-6-(hydroxymethyl)-5-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-2,3,4-triol; Maltose | 9005-84-9 | C12H22O11 | 详情 | 详情 |
| (II) | 13306 | 2-Methyl-1-propanamine; Isobutylamine | 78-81-9 | C4H11N | 详情 | 详情 |
| (III) | 29999 | (2R,3R,4S,5S,6R)-2-[[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-(isobutylamino)tetrahydro-2H-pyran-3-yl]oxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; Isobutylmaltosylamine | C16H31NO10 | 详情 | 详情 | |
| (IV) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (V) | 30000 | N'-(2-Chloroethyl)-N-((2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-2-yl)-N-isobutylurea; 1-(2-Chloroethyl)-3-isobutyl-3-D-maltosylurea | C19H35ClN2O11 | 详情 | 详情 | |
| (VI) | 30001 | (2R,3R,4S,5R,6R)-2-[[(2R,3R,4S,5R,6R)-6-[[[1-(2-chloroethyl)-2-oxohydrazino]carbonyl](isobutyl)amino]-4,5-dinitrosooxy-2-(nitrosooxymethyl)tetrahydro-2H-pyran-3-yl]oxy]-3,5-dinitrosooxy-6-(nitrosooxymethyl)tetrahydro-2H-pyran-4-yl nitrite; 1-(2-Chloroethyl)-3-isobutyl-3-(beta-D-heptanitrosomaltosyl)-1-nitrosourea | C19H27ClN10O19 | 详情 | 详情 |