柔红霉素酮的7-（氨乙基）醚和硫醚

7-(Aminoethyl) ether and thioether of daunomycinone.

作者信息

Acton E M, Tong G L, Mosher C W, Smith T H, Henry D W

出版信息

J Med Chem. 1979 Aug;22(8):922-6. doi: 10.1021/jm00194a007.

Abstract

One-step treatment of daunomycinone with excess 2-aminoethanethiol and 2-aminoethanol in trifluoroacetic acid afforded at C-7 the thioether (77% yield) and ether (30% after recycling), respectively. Stereoselectivity for the natural 7S over the 7R configuration was greater for the ether (97:3) than for the thioether (2.5:1). Esterification of daunomycin at C-7 with beta-alanine was accomplished through the mixed anhydride of Z(OMe)-beta-alanine. Preliminary biological tests suggests that the antitumor and DNA interactive properties of the anthracyclines can be retained in such structures.

摘要

在三氟乙酸中，用过量的2-氨基乙硫醇和2-氨基乙醇对柔红霉素酮进行一步处理，分别在C-7位得到硫醚（产率77%）和醚（循环后产率30%）。醚对天然7S构型相对于7R构型的立体选择性（97:3）高于硫醚（2.5:1）。柔红霉素在C-7位与β-丙氨酸的酯化反应是通过Z(OMe)-β-丙氨酸的混合酸酐完成的。初步生物学测试表明，蒽环类药物的抗肿瘤和DNA相互作用特性可以保留在这类结构中。