用于合成具有抗肿瘤活性的2'-卤代柔红霉素类似物的糖烯的氧卤化反应

Oxyhalogenation of glycals for the synthesis of anti-tumor-active 2'-halo daunorubicin analogs.

作者信息

Horton D, Priebe W

出版信息

Carbohydr Res. 1985 Feb 28;136:391-6. doi: 10.1016/0008-6215(85)85212-5.

Abstract

Alkoxyhalogenation of L-rhamnal diacetate with daunomycinone and N-iodosuccinimide afforded 37% of 7-O- (3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl)daunomycin one (4, NSC 331,962) and 7% of the beta-L-gluco analog (NSC 353,457); a similar procedure with L-fucal diacetate gave 77% of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-talopyranosyl) daunomycinone (NSC 327,472). Compound 4 showed high activity (T/C 247) and low toxicity in the P-388 lymphocytic leukemia screen in mice.

摘要

L-鼠李糖二乙酸酯与柔红霉素酮和N-碘代琥珀酰亚胺进行烷氧基卤化反应，得到37%的7-O-(3,4-二-O-乙酰基-2,6-二脱氧-2-碘-α-L-甘露吡喃糖基)柔红霉素酮(4, NSC 331,962)和7%的β-L-葡萄糖类似物(NSC 353,457)；用L-岩藻糖二乙酸酯进行类似的反应，得到77%的7-O-(3,4-二-O-乙酰基-2,6-二脱氧-2-碘-α-L-塔罗吡喃糖基)柔红霉素酮(NSC 327,472)。化合物4在小鼠P-388淋巴细胞白血病筛选中显示出高活性(T/C 247)和低毒性。