柔红霉素酮和阿霉素酮新糖苷的合成及其抗肿瘤特性

Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone.

作者信息

Arcamone F, Penco S, Vigevani A, Redaelli S, Franchi G, DiMarco A, Casazza A M, Dasdia T, Formelli F, Necco A, Soranzo C

出版信息

J Med Chem. 1975 Jul;18(7):703-7. doi: 10.1021/jm00241a013.

DOI:10.1021/jm00241a013

PMID:168385

Abstract

The synthesis of 4'-epi-daunorubicin and of 4'-epi-adriamycin was performed by condensation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride with daunomycinone or the protected adriamycinone derivative 17, respectively. Both the alpha and beta anomers were obtained and characterized. All new compounds are biologically active in cultured cells and the alpha anomers display noticeable activity in experimental tumors in mice. Interestingly, 4'-epi-adriamycin (4) appears nontoxic to cultured heart cells up to a concentration of 5 mug/ml.

摘要

4'-表柔红霉素和4'-表阿霉素的合成是通过将2,3,6-三脱氧-3-三氟乙酰氨基-4-O-三氟乙酰基-α-L-阿拉伯己吡喃糖基氯分别与柔红霉酮或受保护的阿霉素酮衍生物17缩合来进行的。得到了α和β异头物并对其进行了表征。所有新化合物在培养细胞中均具有生物活性，并且α异头物在小鼠实验肿瘤中显示出显著活性。有趣的是，4'-表阿霉素（4）在浓度高达5μg/ml时对培养的心脏细胞似乎无毒。