Sharma M, Bernacki R J, Paul B, Korytnyk W
Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Carbohydr Res. 1990 May 1;198(2):205-21. doi: 10.1016/0008-6215(90)84293-4.
2-Amino-2,4-dideoxy-4-fluoro- and 2-amino-2,4,6-trideoxy-4, 6-difluoro-D-galactose, and 2-amino-2,4-dideoxy-4-fluoro- and 2-amino-4-deoxy-4, 4-difluoro-D-xylo-hexose were synthesized, as potential modifiers of tumor cell-surface glyco-conjugate, from benzyl 2-acetamido-3-O-benzyl-2-deoxy-4, 6-di-O-mesyl-alpha-D-glucopyranoside and benzyl 2-acetamido-3, 6-di-O-benzyl-2-deoxy-4-O-mesyl-alpha-D-glucopyranoside, which were converted into the corresponding 4,6-difluoro-2,4, 6-trideoxy and 2,4-dideoxy-4-fluoro derivatives. Benzyl 2-acetamido-2-deoxy-4-O-mesyl-alpha-D-galactopyranoside and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-xylo-hexo-4-ulopyra noside were treated with diethylaminosulfur trifluoride to give 2-amino-2,4-dideoxy-4-fluoro-D-glucose and 2-amino-2,4-dideoxy-4, 4-di-fluoro-D-xylo-hexose derivatives, respectively, to give after deprotection the target compounds. Several of the peracetylated sugar derivatives inhibited L1210 tumor-cell growth in vitro at concentrations of 1-5 10(-5) M. The peracetylated derivative of 2-amino-2,4-dideoxy-4-fluoro-D-galactose inhibited protein and glycoconjugate biosynthesis, and also exhibited antitumor activity in mice with L1210 leukemia.
合成了2-氨基-2,4-二脱氧-4-氟-D-半乳糖、2-氨基-2,4,6-三脱氧-4,6-二氟-D-半乳糖、2-氨基-2,4-二脱氧-4-氟-D-木糖己糖和2-氨基-4-脱氧-4,4-二氟-D-木糖己糖，作为肿瘤细胞表面糖缀合物的潜在修饰剂，它们由2-乙酰氨基-3-O-苄基-2-脱氧-4,6-二-O-甲磺酰基-α-D-吡喃葡萄糖苷和2-乙酰氨基-3,6-二-O-苄基-2-脱氧-4-O-甲磺酰基-α-D-吡喃葡萄糖苷合成，这些化合物被转化为相应的4,6-二氟-2,4,6-三脱氧和2,4-二脱氧-4-氟衍生物。2-乙酰氨基-2-脱氧-4-O-甲磺酰基-α-D-吡喃半乳糖苷和2-乙酰氨基-3,6-二-O-苄基-2-脱氧-α-D-木糖-4-己糖醛酸吡喃糖苷分别用二乙氨基三氟化硫处理，得到2-氨基-2,4-二脱氧-4-氟-D-葡萄糖和2-氨基-2,4-二脱氧-4,4-二氟-D-木糖己糖衍生物，脱保护后得到目标化合物。几种全乙酰化糖衍生物在1-5×10⁻⁵ M的浓度下可体外抑制L1210肿瘤细胞生长。2-氨基-2,4-二脱氧-4-氟-D-半乳糖的全乙酰化衍生物可抑制蛋白质和糖缀合物的生物合成，并且在患有L1210白血病的小鼠中也表现出抗肿瘤活性。
