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【结 构 式】

【药物名称】Esorubicin hydrochloride, NSC-267469(free base), IMI-58

【化学名称】4'-Deoxydoxorubicin hydrochloride
      [2S-[2alpha(8R*,10R*),4beta,6beta]]-10-[(4-Aminotetrahydro-6-methyl-2H-pyran-2-yl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione hydrochloride
      (8S,10S)-10-[[(2S,4R,6S)-4-[(Aminotetrahydro-6-methyl-2H-pyran-2-yl)oxy]-8-glycoloyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione hydrochloride

【CA登记号】63950-06-1, 63521-85-7 (free base)

【 分 子 式 】C27H30ClNO10

【 分 子 量 】563.99385

【开发单位】Pfizer (Originator)

【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, Oncolytic Drugs

合成路线1

The sulfonation of methyl N-trifluoroacetyldaunosaminide (I) with mesyl chloride or with 4-bromophenylsulfonyl chloride in pyridine gives the corresponding 4-O-mesyl derivative (II) or 4-O-(4-bromophenylsulfonyl) derivative (IIa); both compounds by reaction with NaI in refluxing butanone yield the 4-iodo compound (III). The hydrogenation of (III) with H2 over Pd/C in methanol, followed by hydrolysis with hot acetic acid yields 4-deoxy-N-trifluoroacetyldaunosaminide (IV), which is esterified with p-nitrobenzoyl chloride in pyridine affording the corresponding p-nitrobenzoyl ester (V). The reaction of (V) with dry HCl in methylene chloride gives 1,4-dideoxy-N-trifluoroacetyldanosaminide (VI), which is condensed with daunomycinone (VII) by means of silver trifluoromethylsulfonate in methylene chloride and hydrolyzed with NaOH to afford 4'-deoxy-daunomycine (VIII). The bromination of (VIII) with Br2 in methanol-dioxane gives 4'-deoxy-14-bromodaunomycine (IX), which is finally hydrolyzed with aqueous sodium formate.

1 Penco, S.; Arcamone, F.; Di Marco, A.; Novel antitumor glycosides of the anthracycline series and process for their preparation. FR 2325659 .
2 Arcamone, F.; Penco, S.; Redaelli, S.; Hanessian, S.; Synthesis and antitumor activity of 4'-deoxydaunorubicin and 4'-deoxyadriamycin. J Med Chem 1976, 19, 1424-25.
3 Robinson, C.P.; Prous, J.; Castaner, J.; ESORUBICIN HYDROCHLORIDE < Rec INNM; USAN >. Drugs Fut 1990, 15, 10, 986.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(A) 18964 4-bromobenzenesulfonyl chloride 98-58-8 C6H4BrClO2S 详情 详情
(IIa) 31180 (2S,3S,4S,6R)-6-methoxy-2-methyl-4-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-3-yl 4-bromobenzenesulfonate C15H17BrF3NO6S 详情 详情
(I) 30693 2,2,2-trifluoro-N-[(2S,3S,4S,6R)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide C9H14F3NO4 详情 详情
(II) 31179 (2S,3S,4S,6R)-6-methoxy-2-methyl-4-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-3-yl methanesulfonate C10H16F3NO6S 详情 详情
(III) 31181 2,2,2-trifluoro-N-[(2S,3R,4S,6R)-3-iodo-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide C9H13F3INO3 详情 详情
(IV) 31182 2,2,2-trifluoro-N-[(2R,4R,6S)-2-hydroxy-6-methyltetrahydro-2H-pyran-4-yl]acetamide C8H12F3NO3 详情 详情
(V) 31183 (2S,4R,6S)-6-methyl-4-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-2-yl 4-nitrobenzoate C15H15F3N2O6 详情 详情
(VI) 31184 N-[(2S,4R,6S)-2-chloro-6-methyltetrahydro-2H-pyran-4-yl]-2,2,2-trifluoroacetamide C8H11ClF3NO2 详情 详情
(VII) 16223 (8S,10S)-8-acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione 21794-55-8 C21H18O8 详情 详情
(VIII) 31185 (8S,10S)-8-acetyl-10-[[(2S,4R,6S)-4-amino-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione C27H29NO9 详情 详情
(IX) 31186 (8S,10S)-10-[[(2S,4R,6S)-4-amino-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-(2-bromoacetyl)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione C27H28BrNO9 详情 详情
Extended Information