Acton E M, Ryan K J, Luetzow A E
J Med Chem. 1977 Nov;20(11):1362-71. doi: 10.1021/jm00221a002.
In the first approach by total synthesis to the structure of the antitumor antibiotic septacidin, analogues have been obtained which show similar inhibition of RNA-DNA synthesis in cultured leukemia L1210 cells and similar activity against transplanted leukemia P388 in mice. In these analogues, the natural aminoheptose moiety is replaced by 4-amino-4-deoxy-and 4-amino-4,6-dideoxy-L-glucose, to retain the natural configuration of the pyranose ring. Also retained is the lipophilic fatty acid-amino acid side chain attached to the 4-amino group and glycosylation at the 6-NH2 of adenine. If the fatty acid chain was shortened from C16 to C6, if the fatty chain was shifted to the glycine unit, or if the glycine unit was omitted, activity was completely lost. However, activity was retained if the C16 chain was shortened only to C12 or if the glycine unit was extended to beta-alanine. Both active and inactive analogues were nonbinding to DNA and nonmutagenic to Salmonella strains. The synthetic approach was to start with a suitably protected sugar (L-fucose and L-galactose), construct the adenine moiety at C-1 introduce a 4-amino group, and finally attach the preformed side chain.
在首次通过全合成方法研究抗肿瘤抗生素隔孢伏革菌素结构的过程中，已获得了一些类似物，这些类似物在培养的白血病L1210细胞中对RNA-DNA合成表现出相似的抑制作用，并且对小鼠移植性白血病P388具有相似的活性。在这些类似物中，天然的氨基庚糖部分被4-氨基-4-脱氧-L-葡萄糖和4-氨基-4,6-二脱氧-L-葡萄糖取代，以保留吡喃糖环的天然构型。连接在4-氨基上的亲脂性脂肪酸-氨基酸侧链以及腺嘌呤6-NH2处的糖基化也得以保留。如果脂肪酸链从C16缩短至C6，如果脂肪酸链转移至甘氨酸单元，或者如果省略甘氨酸单元，活性则完全丧失。然而，如果C16链仅缩短至C12，或者甘氨酸单元扩展为β-丙氨酸，则活性得以保留。活性和非活性类似物均不与DNA结合，对沙门氏菌菌株也无致突变性。合成方法是从适当保护的糖（L-岩藻糖和L-半乳糖）开始，在C-1处构建腺嘌呤部分，引入4-氨基，最后连接预先形成的侧链。
