2'-溴-和2'-氯-3'-乙酰氧基-3'-脱氨基柔红霉素类似物的合成及其抗肿瘤活性

Synthesis and antitumor activity of 2'-bromo- and 2'-chloro-3'-acetoxy-3'-deaminodaunorubicin analogs.

作者信息

Horton D, Priebe W, Varela O

出版信息

Carbohydr Res. 1985 Dec 1;144(2):305-15. doi: 10.1016/s0008-6215(00)90678-5.

Abstract

Bromination of 3,4-di-O-acetyl-L-rhamnal (7) and subsequent glycosidic coupling under Koenigs-Knorr conditions with daunomycinone gave a mixture of three compounds having the beta-L-gluco (10), alpha-L-gluco (11), and alpha-L-manno (12) configurations. Analogous bromination of 3,4-di-O-acetyl-L-fucal (13) followed by coupling with daunomycinone gave a mixture of three glycosides having the beta-L-galacto (16), alpha-L-galacto (17), and alpha-L-talo (18) configurations. Chlorination of 7 and coupling with daunomycinone in the presence of silver triflate gave products having the alpha-L-gluco (21) and alpha-L-manno (22) configurations, whereas 13, under similar conditions, gave only one stereoisomeric product, that having the alpha-L-galacto (24) configuration. Compounds 12 and 22 showed high in vivo activity in the P-388 lymphocytic leukemia assay.

摘要

3,4 - 二 - O - 乙酰基 - L - 鼠李糖醛（7）的溴化反应，以及随后在柯尼希斯 - 克诺尔条件下与柔红霉素酮进行糖苷偶联反应，得到了三种具有β - L - 葡萄糖（10）、α - L - 葡萄糖（11）和α - L - 甘露糖（12）构型的化合物混合物。3,4 - 二 - O - 乙酰基 - L - 岩藻糖（13）进行类似的溴化反应，随后与柔红霉素酮偶联，得到了三种具有β - L - 半乳糖（16）、α - L - 半乳糖（17）和α - L - 塔罗糖（18）构型的糖苷混合物。7在三氟甲磺酸银存在下氯化并与柔红霉素酮偶联，得到了具有α - L - 葡萄糖（21）和α - L - 甘露糖（22）构型的产物，而13在类似条件下仅得到一种立体异构体产物，即具有α - L - 半乳糖（24）构型的产物。化合物12和22在P - 388淋巴细胞白血病试验中显示出高体内活性。