Montgomery J A, Thomas H J
J Med Chem. 1979 Sep;22(9):1109-13. doi: 10.1021/jm00195a020.
3-Deoxyl-1,2-O-isopropylidine-3-(3-methylureido)-alpha-D-ribofuranose (2) was converted to 1,2,5-tri-O-acetyl-3-deoxy-3-(3-acetyl-3-methylureido)-D-ribofuranose (4) and the corresponding glycosyl chloride (7). These sugars were converted to the 3-deoxy-3-(3-methylureido)-beta-D-ribofuranosyl derivatives of adenine (6c), 2-chloroadenine (6d), cytosine (6f), and uracil (6g). Nitrosation of these nucleosides gave the corresponding 3-methyl-3-nitrosoureidonucleosides 8c,d,f,g. 5'-Amino-5'-doxyadenosine (10a), 5'-amino-5'-deoxyuridine (10b), and 5'-amino-5'-deoxycytidine (10c) were all converted to the corresponding 5'-(methylureido)-5'-deoxynucleosides 15a--c by reaction with methyl isocyanate. Nitrosation of these compounds gave the methylnitrosoureidonucleosides 16a--c. These nitrosoureas, potential active-site-directed irreversible enzyme inhibitors, showed little cytotoxicity or activity against leukemia L1210 in vivo.
3-脱氧-1,2-O-异亚丙基-3-(3-甲基脲基)-α-D-呋喃核糖(2)被转化为1,2,5-三-O-乙酰基-3-脱氧-3-(3-乙酰基-3-甲基脲基)-D-呋喃核糖(4)和相应的糖基氯(7)。这些糖被转化为腺嘌呤(6c)、2-氯腺嘌呤(6d)、胞嘧啶(6f)和尿嘧啶(6g)的3-脱氧-3-(3-甲基脲基)-β-D-呋喃核糖基衍生物。这些核苷的亚硝化反应得到相应的3-甲基-3-亚硝基脲基核苷8c、d、f、g。5'-氨基-5'-脱氧腺苷(10a)、5'-氨基-5'-脱氧尿苷(10b)和5'-氨基-5'-脱氧胞苷(10c)通过与异氰酸甲酯反应均被转化为相应的5'-(甲基脲基)-5'-脱氧核苷15a - c。这些化合物的亚硝化反应得到甲基亚硝基脲基核苷16a - c。这些亚硝基脲类化合物作为潜在的活性位点导向不可逆酶抑制剂，在体内对白血病L1210几乎没有细胞毒性或活性。
