Taylor W G, Leadbetter G, Fost D L, Remers W A
J Med Chem. 1977 Jan;20(1):138-41. doi: 10.1021/jm00211a029.
cis-1-Acetamido-2-acetoxy-7-methoxy-N-methylmitosene was prepared in 11 steps from 7-methoxy-6-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-one by a route involving bromination of the pyrrolidineenamine or trimethylsilyl enol ether of starting material, displacement of bromide by acetate, oxime formation, and reductive acetylation, followed by elaboration of the quinone and methyl carbamate functions according to previously established methods. An unsubstituted carbamate could not be prepared. The mitosene thus synthesized differs from previously reported 1,2-disubstituted mitosenes, which are derived from the solvolysis of mitomycins, in that it has the opposite arrangement of oxygen and nitrogen substituents at the 1 and 2 positions. It showed antibacterial activities in disk-plate assays superior to those of cis-diacetylapomitomycin A and equivalent to those of certain 1-substituted mitosenes; however, it was less active than mitomycin A in these assays. It was inactive in inducing lambda-bacteriophage in Escherichia coli and inactive against P388 leukemia in mice. In contrast, certain 1-substituted mitosenes were active in prophage induction and 2b and mitomycin A were active in both assays.
顺式-1-乙酰氨基-2-乙酰氧基-7-甲氧基-N-甲基丝裂霉素由7-甲氧基-6-甲基-2,3-二氢-1H-吡咯并[1,2-a]吲哚-1-酮经11步反应制得，其合成路线包括起始原料吡咯烷烯胺或三甲基硅基烯醇醚的溴化、溴被乙酸根取代、肟的形成和还原乙酰化，随后根据先前建立的方法对醌和甲基氨基甲酸酯官能团进行修饰。无法制备未取代的氨基甲酸酯。如此合成的丝裂霉素与先前报道的源自丝裂霉素溶剂解的1,2-二取代丝裂霉素不同，其在1和2位上氧和氮取代基的排列相反。在纸片法试验中，它显示出优于顺式二乙酰阿波丝裂霉素A的抗菌活性，与某些1-取代丝裂霉素相当；然而，在这些试验中，它的活性低于丝裂霉素A。它在诱导大肠杆菌中的λ噬菌体方面无活性，对小鼠P388白血病也无活性。相比之下，某些1-取代丝裂霉素在原噬菌体诱导中有活性，而2b和丝裂霉素A在两种试验中均有活性。
