(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 -Drug Synthesis Database

【结构式】

【分子编号】30001

【品名】(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

【CA登记号】

【分子式】C₁₉H₂₇ClN₁₀O₁₉

【分子量】734.93208

【元素组成】C 31.05% H 3.7% Cl 4.82% N 19.06% O 41.36%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VI)

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.

参考文献中间体

合成目标

【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

Extended Information